More Evidence That Higher Education May Lower Risk of Alzheimer’s Disease

MedicalResearch.com Interview with:

Susanna C. Larsson, PhD Associate Professor, Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden

Dr. Larsson

Susanna C. Larsson, PhD
Associate Professor, Karolinska Institutet,
Institute of Environmental Medicine,
Stockholm, Sweden

MedicalResearch.com: What is the background for this study?

Response: The causes of Alzheimer’s disease are largely unknown and there are currently no medical treatments that can halt or reverse its effects. This has led to growing interest in identifying risk factors for Alzheimer’s that are amenable to modification. Several observational studies have found that education and various lifestyle and vascular risk factors are associated with the risk of Alzheimer’s disease, but whether these factors actually cause Alzheimer’s is unclear.

We used a genetic epidemiologic method known as ‘Mendelian randomization’. This method involves the use of genes with an impact on the modifiable risk factor – for example, genes linked to education or intelligence – and assessing whether these genes are also associated with the disease. If a gene with an impact on the modifiable risk factor is also associated with the disease, then this provides strong evidence that the risk factor is a cause of the disease.

MedicalResearch.com:  What are the main findings?

Response: Our results, based on aggregated genetic data from 17 000 Alzheimer’s disease patients and 37 000 healthy controls, revealed that genetic variants that predict higher education were clearly associated with a reduced risk of Alzheimer’s disease. A possible explanation for this link is ‘cognitive reserve’, which refers to the ability to recruit and use alternative brain networks or structures not normally used to compensate for brain ageing. Previous research has shown that high education increases this reserve.

We found suggestive evidence for possible associations of intelligence, circulating vitamin D, coffee consumption, and smoking with risk of Alzheimer’s disease. There was no evidence for a causal link with other modifiable factors, such as vascular risk factors.

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Could Lithium Lower Risk Of Alzheimer’s Disease?

MedicalResearch.com Interview with:

Val Andrew Fajardo, PhD. NSERC Postdoctoral Fellow | Centre for Bone and Muscle Health Brock University | Department of Health Sciences St. Catharines, ON, Canada 

Dr. Fajardo

Val Andrew Fajardo, PhD.
NSERC Postdoctoral Fellow | Centre for Bone and Muscle Health
Brock University | Department of Health Sciences
St. Catharines, ON, Canada 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Lithium is best known for its role as a mood stabilizer, and several ecological studies across a number of different regions have shown that trace levels of lithium in tap water can exert its mood stabilizing effect and reduce rates of suicide, crime, and homicide.

The results from our study show that these trace levels of lithium could also potentially protect against Alzheimer’s disease.  These findings are actually supported by several years of research using pre-clinical and clinical models to demonstrate low-dose lithium’s neuroprotective effect against Alzheimer’s disease. In addition, we also found that trace lithium in tap water may potentially protect against obesity and diabetes – an effect that is also supported with previous literature.  In fact, some of the earlier reports of lithium’s effect of increasing insulin sensitivity and improving glucose metabolism were first published in the 1920s.  Finally, we found that trace lithium’s effect on Alzheimer’s disease may be partly mediated by its effect on obesity and diabetes.

My collaborator Dr. Rebecca MacPherson who is an expert on Alzheimer’s disease as a metabolic disorder explains that this effect is in support of recent research demonstrating that obesity and diabetes are important risk factors in the development of Alzheimer’s disease.  So interventions aiming to reduce obesity and diabetes such as physical activity can go a long way in lowering risk for Alzheimer’s disease, which is also something we present in our study.

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Amyloid Deposits In Persons Without Dementia May Be First Sign of Alzheimer’s Disease 

MedicalResearch.com Interview with:

Willemijn Jansen, PhD  Postdoctoral researcher Department of Psychiatry & Neuropsychology Maastricht University Medical Center School for Mental Health and Neuroscience Alzheimer Center Limburg 

Dr. Jansen

Willemijn Jansen, PhD
Postdoctoral researcher
Department of Psychiatry & Neuropsychology
Maastricht University Medical Center
School for Mental Health and Neuroscience
Alzheimer Center Limburg 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer’s disease (AD), starting decades prior to dementia onset. About 25% of cognitively normal elderly and 50% of patients with mild cognitive impairment (MCI) have biomarker evidence of amyloid pathology. These persons are at increased risk for developing AD-type dementia, but the extent to which amyloid-β aggregation affects cognitive function in persons without dementia is unclear. This is important to know for a better understanding of the course of Alzheimer’s disease and for the design of AD prevention trials.

We here investigate the association between amyloid plaques and memory scores, using data from 53 international studies included in the Amyloid Biomarker study. Cognitively healthy elderly people with plaques have a low memory score twice as often as these persons without plaques. MCI patients with plaques had 20% more often low memory and low global cognition scores than MCI patients without plaques.

We further observed 10- to 15-year intervals between the onset of amyloid positivity and emergence of low memory scores in cognitively healthy persons.

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Sleep Apnea Increases Amyloid Load In Brain, A Hallmark of Alzheimer’s Disease

MedicalResearch.com Interview with:

Ricardo S Osorio MD Center for Brain Health Department of Psychiatry Center of Excellence on Brain Aging NYU Langone Medical Center New York, NY 10016, USA

Dr. Osorio

Ricardo S Osorio MD
Center for Brain Health
Department of Psychiatry
Center of Excellence on Brain Aging
NYU Langone Medical Center
New York, NY 10016, USA 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This was a study that was performed in a group of healthy normal elderly from the community that volunteered for studies on memory and aging.

The main findings were that sleep apnea was very common, in almost all cases undiagnosed, and that it was associated with a longitudinal increase in amyloid burden which is considered one of the hallmark lesions of Alzheimer’s disease

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Novel Brain Imaging May Detect Preclinical Alzheimer’s Disease

MedicalResearch.com Interview with:
Dr. Sanja Josef Golubic, dr. sc

Department of Physics, Faculty of Science
University of Zagreb, Croatia

MedicalResearch.com: What is the background for this study?

Response: Our study was aimed to search the topological biomarker of Alzheimer’s disease. A recent evidences suggest that the decades long progression of brain degeneration that is irreversible by the stage of symptomatic Alzheimer’s disease, may account for failures to develop successful disease-modifying therapies. Currently, there is a pressing worldwide search for a marker of very early, possibly reversible, pathological changes related to Alzheimer’s disease in still cognitively intact individuals, that could provide a critical opportunity for evolving of efficient therapeutic interventions.

Three years ago we reported the discovery of the novel, fast brain pathway specialized for rapid processing of the simple tones. We named it gating loop. Gating loop directly links auditory brain areas to prefrontal brain area. We have also noticed the high sensitivity of the gating loop processing on AD pathology. It was inspiration to focus our Alzheimer’s disease biomarker search in the direction of prefrontal brain activation during listening of simple tones.

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Gene Helps Explain Why More Women Than Men Have Alzheimer’s

MedicalResearch.com Interview with:

Arthur W. Toga PhD Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences, Radiology and Engineering Ghada Irani Chair in Neuroscience Director, USC Mark and Mary Stevens Neuroimaging and informatics institute USC Institute for Neuroimaging and Informatics Keck School of Medicine of USC University of Southern California Los Angeles, CA  90032

Dr. Toga

Arthur W. Toga PhD
Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences,
Radiology and Engineering
Ghada Irani Chair in Neuroscience
Director, USC Mark and Mary Stevens Neuroimaging and informatics institute
USC Institute for Neuroimaging and Informatics
Keck School of Medicine of USC
University of Southern California
Los Angeles, CA  90032 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The ε4 allele of the Apolipoprotein E (APOE) gene is the main genetic risk factor for late-onset Alzheimer’s disease.  This study reexamines and corrects the sex-dependent risks that white men and women with one copy of the ε4 allele face for developing Alzheimer’s disease using a very large data set of 57,979 North Americans and Europeans from the Global Alzheimer’s Association Interactive Network (GAAIN).

The study results show that these men and women between the ages of 55 and 85 have the same odds of developing Alzheimer’s disease, with the exception that women face significantly higher risks than men between the ages of 65 and 75.  Further, these women showed increased risk over men between the ages of 55 and 70 for mild cognitive impairment (MCI), which is often a transitional phase to dementia.

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Alzheimer’s: Antidepressants Increase Risk of Head and Traumatic Brain Injuries

MedicalResearch.com Interview with:

Heidi Taipale, PhD Pharm Senior Researcher School of Pharmacy, University of Eastern Finland; and Department of Clinical Neuroscience Karolinska Institutet 

Dr. Taipale

Heidi Taipale, PhD Pharm
Senior Researcher
School of Pharmacy, University of Eastern Finland; and
Department of Clinical Neuroscience
Karolinska Institutet 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Antidepressant use among older persons has been associated with an increased risk of falling and fall-related events, such as hip fractures, in previous studies. Our previous study identified risk of hip fractures in antidepressant among persons with Alzheimer’s disease. As falling is the main causal factor for head traumas and traumatic brain injuries among older persons, we hypothesized that antidepressant use could also be associated with these injuries.

We utilized a nationwide cohort of 70,718 persons newly diagnosed with Alzheimer’s disease, identified from the Finnish registers. The risk of head injuries and traumatic brain injuries was compared between persons initiating antidepressant use and comparison persons of the same age, gender and time since they received diagnoses of Alzheimer’s disease but not using antidepressants. We found a 40-percent increased risk of head injuries and 30-percent increased risk of traumatic brain injuries associated with antidepressant use. Antidepressant use was associated with a higher risk of head injuries especially at the beginning of use – during the first 30 days – but the risk persisted even longer, up to two years. The association was also confirmed in a study design comparing time periods within the same person, thus eliminating selective factors. Continue reading

Disadvantaged Neighborhoods Help Explain Some Of Alzheimer’s Disease Racial Disparities

MedicalResearch.com Interview with:

Amy Kind, M.D., Ph.D. Associate Professor, Division of Geriatrics Director, Department of Medicine Health Services and Care Research Program University of Wisconsin School of Medicine and Public Health and Associate Director- Clinical Geriatrics Research, Education and Clinical Center (GRECC) William S. Middleton Veteran’s Affairs Hospital

Dr. Amy Kind

Amy Kind, M.D., Ph.D.
Associate Professor, Division of Geriatrics
Director, Department of Medicine Health Services and Care Research Program
University of Wisconsin School of Medicine and Public Health and
Associate Director- Clinical
Geriatrics Research, Education and Clinical Center (GRECC)
William S. Middleton Veteran’s Affairs Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Background: Dementia due to Alzheimer’s Disease (AD) disproportionately impacts racial/ethnic minorities and the socioeconomically disadvantaged—populations often exposed to neighborhood disadvantage. Neighborhood disadvantage is associated with education, health behaviors and mortality. Health improves with moving to less disadvantaged neighborhoods (Ludwig, Science 2012). Although studies have linked neighborhood disadvantage to diseases like diabetes and cancer, little is known about its effect on development of dementia.

Objective:  To examine the association between neighborhood disadvantage, baseline cognition, and CSF biomarkers of Alzheimer’s Disease among participants in the WRAP study, comprising a cohort of late-middle-aged adults enriched for parental family history of AD.

Methods:  We created and validated neighborhood-level quantifications of socioeconomic contextual disadvantage for the full US—over 34 million Zip+4 codes—employing the latest American Community Survey and Census data. This metric–the Area Deprivation Index (ADI)–incorporates poverty, education, housing and employment indicators; predicts disparity-related health outcomes; and is employed by Maryland and Medicare through our provision. We used standard techniques to geocode all WRAP subjects with a documented address (N= 1479). WRAP participants were ranked into deciles of neighborhood disadvantage, by ADI. Baseline cognitive function (indexed by factor scores) and CSF biomarker outcomes for levels of Aβ42 and P-tau181 (n=153 with CSF samples) were examined by neighborhood disadvantage decile.

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Dementia Care Management Improved Quality of Life For Both Caregivers and Patients With Dementia

MedicalResearch.com Interview with:

Jochen René Thyrian, PhD German Center for Neurodegenerative Diseases (DZNE) Greifswald, Germany     

Dr. Thyrian

Jochen René Thyrian, PhD
German Center for Neurodegenerative Diseases (DZNE)
Greifswald, Germany

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Dementia presents a challenge to the health care systems worldwide. People with dementia (PWD) need comprehensive medical, nursing, psychological and social support to delay the progression of disease and sustain autonomy and social inclusion. Evidence-based interventions alleviate the burden of disease for PwD and their caregivers, as no curative treatment is currently available. Involving caregivers is important because they provide the largest proportion of care for PwD. General physicians in residency have been identified as the first point of contact for PwD and is thus a promising setting for identification, comprehensive needs assessment and initiating dementia-specific treatment and care.

In this study we tested the effectiveness and safety of a model of collaborative care, Dementia Care Management (DCM) on patient-oriented outcomes in n=634 people screened positive for dementia in primary care. DCM is provided by specifically trained nurses, supported by a computerized intervention management system, in close cooperation with the treating physician at the people´s homes. Recommendations for improving treatment and care were based on a comprehensive needs assessment, discussed interprofessionally and their implementation monitored/ adjusted over the course of 6-12 months

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Obstructive Sleep Apnea May Accelerate Alzheimer’s Disease

MedicalResearch.com Interview with:

O. Michael Bubu, M.D., M.P.H., C.P.H Wheaton College

Dr. Bubu

O. Michael Bubu, M.D., M.P.H., C.P.H
Wheaton College

MedicalResearch.com: What is the background for this study?

  • Obstructive Sleep Apnea (OSA) and Alzheimer’s disease (AD) are both chronic disease conditions that are highly prevalent, cause significant morbidity and mortality to those afflicted, and have an enormous socio-economic impact. Recent human and animal studies describe associations between Sleep Disordered Breathing (SDB) and Alzheimer’s Disease (AD). However, whether OSA accelerates longitudinal increases in amyloid (Aβ) burden in MCI patients is presently unclear.
  • In this study, we examined the effect of Obstructive Sleep Apnea (OSA) on longitudinal changes in brain amyloid deposition, and Alzheimer’s disease (AD) Cerebrospinal fluid (CSF) biomarkers including CSF beta-amyloid 42 peptide (Aβ-42), CSF TAU protein, CSF phosphorylated TAU protein (PTAU) in Cognitive Normal (CN), Mild Cognitive Impairment (MCI) and AD elderly. Brain amyloid (Aβ) burden, CSF Abeta42 and tau proteins are biomarkers (measurable substances whose presence are indicative) of AD-associated pathologic changes in the brain.
  • Data from 1639 subjects (516 CN, 798 MCI and 325 AD, mean ages = 74.4 ± 5.8; 73.4 ± 7.4 and 75.1 ± 7.8 respectively), in the Alzheimer’s disease Neuroimaging Initiative (ADNI) database was used. OSA was self-reported and participants were labeled OSA positive, or OSA negative (mean ages = 72.3 ± 7.1; and 73.9 ± 7.3 respectively). Statistical analyses were conductedto examine whether OSA positive compared to OSA negative participants experienced significant differences in the rate of change of AD biomarkers over time (mean = 2.52 ± 0.51 years) in each group (CN, MCI and AD). Both OSA positives and negatives were similar in age, APOE e4 status, and history of cardiovascular disease. The final models controlled for sex, body mass index (BMI), and Continuous Pulmonary Airway Pressure (CPAP) use.

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Diet Rich in Anti-Inflammatory Foods May Help Preserve Brain Function

MedicalResearch.com Interview with:
Yian Gu, PhD
Assistant Professor of Neuropsychology (in Neurology and
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain)
Columbia University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have previously shown that elderly individuals who consume healthier diet (certain foods, nutrients, and dietary patterns) have larger brain volume, better cognition, and lower risk of developing Alzheimer’s disease.

The current study aimed to examine the biological mechanisms for the relationship between diet and brain/cognitive health

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Daily Crossword Puzzles May Help Sustain Brain Function As We Age

MedicalResearch.com Interview with:

Professor Keith A. Wesnes BSc PhD FSS CPsychol FBPsS Head Honcho, Wesnes Cognition Ltd Professor of Cognitive Neuroscience, Medical School, University of Exeter, UK Visiting Professor, Department of Psychology, Northumbria University, Newcastle, UK Adjunct Professor, Centre for Human Psychopharmacology, Swinburne University, Melbourne, Australia Visiting Professor, Medicinal Plant Research Group, Newcastle University, UK Wesnes Cognition Ltd, Little Paddock, Streatley Hill, Streatley on Thames UK

Prof. Wesnes

Professor Keith A. Wesnes
BSc PhD FSS CPsychol FBPsS
Head Honcho, Wesnes Cognition Ltd
Professor of Cognitive Neuroscience, Medical School, University of Exeter, UK
Visiting Professor, Department of Psychology
Northumbria University, Newcastle, UK
Adjunct Professor, Centre for Human Psychopharmacology, Swinburne University, Melbourne, Australia
Visiting Professor, Medicinal Plant Research Group
Newcastle University, UK
Wesnes Cognition Ltd, Little Paddock, Streatley Hill, Streatley on Thames UK 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This data we reported were taken from the PROTECT study, a 10-year research programme being conducted jointly by Kings College London and the University of Exeter Medical School. It started in November 2015 and over 20,000 individuals aged 50 to 96 years have enrolled.

A highly novel feature of the study is that it is run entirely remotely, the participants logging on via the internet at home and providing demographic and life style information, and also performing online cognitive tasks of key aspects of cognitive function. The tasks are from two well-validated systems, CogTrack and the PROTECT test system, and assess major aspects of cognitive function including focused and sustained attention, information processing, reasoning and a range of aspects of memory.

One of the lifestyle questions was ‘How frequently do you engage in word puzzles, e.g. crosswords?’ and the 6 possible answers were: never; occasionally; monthly; weekly; daily; more than once per day. We analysed the cognitive data from 17,677 individuals who had answered the question, and found that the more often the participants reported engaging in such puzzles, the better their cognitive function on each of the 9 cognitive tasks they performed. The group who never performed such puzzles were poorest on all measures, and the improvements were mostly incremental as the frequency of use increased. The findings were highly statistically reliable, and we controlled for factors including age, gender and education. To evaluate the magnitudes of these benefits, we calculated the average decline over the age-range on the various tasks in the study population. The average difference between those who ‘never’ did puzzles to those who did so ‘more than once a day’ was equivalent to 11 years of ageing; and between those who never did puzzles and all those who did was 8 years.

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Patients and Providers Feel Amyloid PET Scanning Diagnosis of Alzheimer’s Disease Beneficial

MedicalResearch.com Interview with:

Liana Apostolova, MD, MSc, FAAN Barbara and Peer Baekgaard Professor  in Alzheimer's Disease Research Professor in Neurology, Radiology. Medical and Molecular Genetics Indiana University School of Medicine Indiana Alzheimer's Disease Center Indianapolis, IN 46202

Dr. Apostolova

Liana Apostolova, MD, MSc, FAAN
Barbara and Peer Baekgaard Professor  in Alzheimer’s Disease Research
Professor in Neurology, Radiology. Medical and Molecular Genetics
Indiana University School of Medicine
Indiana Alzheimer’s Disease Center
Indianapolis, IN 46202

MedicalResearch.com: What is the background for this study?

Response: While many studies have evaluated the diagnostic or prognostic implications associated with amyloid PET, few have explored its effects on the patient or caregiver. Amyloid imaging does not only help clinicians with their diagnosis and management. It also affects patient and caregiver decisions related to lifestyle, financial and long-term care planning, and at times also employment. Few studies to date have explored patient and caregiver views on the clinical use of amyloid PET and the potential benefits they could derive from having more precise diagnosis.

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Familial History Improves Predictive Value of TOMM40 Gene in Alzheimer’s Disease

MedicalResearch.com Interview with:

Auriel Willette, M.S., Ph.D. Assistant Professor Departments of Food Science and Human Nutrition and Psychology Iowa State University

Dr. Willette

Auriel Willette, M.S., Ph.D.
Assistant Professor
Departments of Food Science and Human Nutrition and Psychology
Iowa State University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is a gene that regulates the width of the outer mitochondrial pore, facilitating the transport of ribosomal pre-proteins into the inner mitochondrial matrix for translational modification into functional proteins. In 2010, Dr. Allen Roses, who discovered the Apolipoprotein E (APOE) gene, Dr. Michael Lutz, and other colleagues found that a variation in poly-T length at locus rs10524523 (‘523) within intron 6 predicted Alzheimer’s disease onset. Specifically, a “long” versus “short” poly-T length was related to earlier age of onset by 8 years.

However, several multi-cohort studies either failed to replicate the findings or found the opposite relationship, where a “long” or “very long” poly-T length was related to later age of onset. The literature has remained mixed to this day.

We were interested in testing factors that might change the relationship between TOMM40 and both cognitive decline and risk for having Alzheimer’s disease. It is known that a family history (FH) of Alzheimer’s disease has been associated with mitochondrial dysfunction. We reasoned, then, that FH may interact with TOMM40 to modulate how it was related to our outcomes of interest. We investigated this hypothesis in two separate cohorts: the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a late middle-aged cohort, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a well-characterized sample of aged participants from across the Alzheimer’s spectrum.

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Can Greebles Help Identify People At Risk of Alzheimer’s Disease?

MedicalResearch.com Interview with:
Emily Mason, Ph.D.

Postdoctoral Associate
Department of Neurological Surgery
University of Louisville

MedicalResearch.com: What is the background for this study? What are the main findings?

Family History of Alzheimer’s Disease is Associated with Impaired Perceptual Discrimination of Novel Objects

Family History of Alzheimer’s Disease is Associated with Impaired Perceptual Discrimination of Novel Objects

Response: Alzheimer’s disease is a devastating neurodegenerative disease that currently affects one in eight Americans over the age of 65. Unfortunately, there is still no treatment that will halt or reverse the pathology associated with Alzheimer’s disease. One of the reasons for this may be that we still don’t fully understand what is happening in the very earliest stages of the disease. Previous studies have shown that one of the pathological hallmarks of the disease, called “tau tangles,” begins to accumulate in a specific area of the brain called the medial temporal lobe decades before people are typically diagnosed with Alzheimer’s disease. We wondered if we could use cognitive tests targeted to structures in the medial temporal lobe to pick up very subtle behavioral changes in people who were at increased risk for Alzheimer’s disease. We examined people who were in their 40s and 50s, which is a time when if any differences could be detected, it’s possible that pathology may be reversible.

Using a cognitive task called “odd man out” that can be easily implemented using a computer, we found that subjects at risk for Alzheimer’s disease tended to do worse in identifying differences between objects called Greebles. These objects are highly visually similar, and most people have never seen them before. Those two things make this task very difficult. We believe that this study lays some of the groundwork in developing cognitive tests targeted at relatively young subjects who may be in the very earliest stages of the disease.

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Safety and Immunogenicity of the Tau Vaccine AADvac1 in Patients with Alzheimer’s Disease

MedicalResearch.com Interview with:

Petr Novak, MD, PhD AXON Neuroscience Bratislava, Slovakia

Dr. Petr Novak

Petr Novak, MD, PhD
AXON Neuroscience
Bratislava, Slovakia

MedicalResearch.com: What is the background for this study?

Response: Alzheimer’s disease is a complex, multifactorial disorder, with many-faceted neuropathology. A hallmark finding is the co-existence of neurofibrillary pathology (such as neurofibrillary tangles) composed of tau protein, and amyloid-β pathology (plaques) [1].

Neurofibrillary pathology is closely correlated with cognitive impairment in Alzheimer’s disease [2], while support for the role amyloid in the disease pathogenesis comes from the ability of certain mutations to induce AD in an autosomal-dominant fashion [3].

The field has explored various anti-amyloid therapies to great extent, and continues to do so with undiminished effort [4]; meanwhile, there is a noticeable paucity of investigated therapies aimed at neurofibrillary tau protein pathology, despite the ability of tau protein dysfunction to cause a multitude of neurodegenerative disorders, collectively named “tauopathies” [5].

AADvac1 is the first tau-targeted immunotherapy investigated in humans [6], a pioneering effort to target the component of AD neuropathology that is proximal to neuronal damage and cognitive loss, and thus to halt or slow the progression of Alzheimer’s disease.

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Early Use of Gene Therapy May Stop Plaques of Alzheimer’s Disease

MedicalResearch.com Interview with:

Dr. Magdalena Sastre PhD Faculty of Medicine, Department of Medicine Senior Lecturer Imperial College London

Dr. Magdalena Sastre

Dr. Magdalena Sastre PhD
Faculty of Medicine, Department of Medicine
Senior Lecturer
Imperial College London

MedicalResearch.com: What is the background for this study?

Response: Alzheimer’s disease is the most common neurodegenerative disorder, affecting over 45 million people around the world. Currently, there are no therapies to cure or stop the progression of the disease. Here, we have developed a gene therapy approach whereby we delivered a factor called PGC-1α, which regulates the expression of genes involved in metabolism, inflammation and oxidative stress in the brain of transgenic mice. This factor is also involved in the regulation of energy in the cells, because it controls the genesis of mitochondria and in the generation of amyloid-β, the main component of the neuritic plaques present in the brains of Alzheimer’s disease patients.

We have found that the animals with Alzheimer’s pathology treated with PGC-1α develop less amyloid plaques in the brain, perform memory tasks as well as healthy mice and do not have neuronal loss in the brain areas affected by the disease.

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Inflammatory Biomarkers May Presage Development of Alzheimer’s

MedicalResearch.com Interview with:

Inflammatory Biomarkers May Presage Development of Alzheimer's

Prof. Paul Morgan

Professor B. Paul Morgan
Director, Systems Immunity Research Institute
Institute of Infection and Immunity
School of Medicine
Cardiff University

MedicalResearch.com: What is the background for this study?

Response: Inflammation is a normal response of the body to infection or injury; however, it is well known that inflammation also has a dark side and when it escapes normal controls can cause disease. Some illnesses, like rheumatoid arthritis, have been known for many years to be caused by rogue inflammation and most of the drugs used to treat work by suppressing the inflammation (anti-inflammatories). More recently, it has become clear that inflammation is behind many other diseases that were previously thought of as diseases of ageing caused by wear and tear and lifestyle – these include heart disease and some brain diseases, notably Alzheimer’s disease the commonest cause of dementia. Evidence that inflammation is one of the drivers of disease has come from many sources, including some where it was noticed that people on long-term anti-inflammatory drugs for other reasons appeared to be protected from developing Alzheimer’s disease.

A problem is that Alzheimer’s disease, despite the name, is not a single disease but rather a group of conditions with similar symptoms, and inflammation is likely to be a cause in only some of the patients; further, most of the inflammation might be occurring very early in the disease, even before symptoms are obvious. So, there is an urgent need for a simple test or set of tests that can be used in individuals with the very earliest hints of Alzheimer’s disease – mild memory loss – that will pick out those who have brain inflammation and are most likely to develop Alzheimer’s disease. It might then be possible to treat this select group with anti-inflammatory drugs that will reduce brain inflammation and slow or stop progression of the disease.

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Study Supportive of Modest Effect of Cognitive Activity on Prevention of Dementia

MedicalResearch.com Interview with:

Deborah Blacker MD, ScD Director of the Gerontology Research Unit Department of Psychiatry Massachusetts General Hospital

Dr. Deborah Blacker

Deborah Blacker MD, ScD
Director of the Gerontology Research Unit
Department of Psychiatry
Massachusetts General Hospital

MedicalResearch.com: What is the background for this study? What are the main findings

Response: Many observational studies have found that those who are cognitively active have a lower risk of developing Alzheimer’s disease or any type of
dementia.

However, we and others have been concerned that these findings
might be spurious due to two potential biases:

  • 1) “confounding,” meaning that those who are cognitively active have lower rates of Alzheimer’s disease for another reason, in particular the effect of greater education,
    which is associated with both lower risk of Alzheimer’s and higher levels
    of cognitive activity; and
  • 2) “reverse causation,” meaning that theassociation could be due to a reduction in cognitive activity among those already in the long preclinical phase of cognitive decline before Alzheimer’s dementia (rather than the lack of cognitive activity causing
    the Alzheimer’s).

    Our study performed a systematic review of the literature on the association, and then a set of bias analyses to assess whether confounding or reverse causation could account for the observed associations.

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Multicountry Assesses Dietary Risk Factors for Alzheimer’s Disease

MedicalResearch.com Interview with:

William B. Grant, Ph.D. Director, Sunlight, Nutrition, and Health Research Center San Francisco, CA www.sunarc.org,

Dr. William Grant

William B. Grant, Ph.D.
Director, Sunlight, Nutrition, and Health Research Center
San Francisco, CA
www.sunarc.org

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The present study is the culmination of 20 years of investigating dietary links to Alzheimer’s disease (AD). I am a physicist by training and spent my salaried career as an atmospheric scientist. In the 1990s while studying the effect of acid rain and ozone on eastern hardwood forests, I became familiar with the geographical ecological study approach. In this approach, populations are defined geographically, such as by state or country, and health outcomes are compared statistically with risk-modifying factors. Ecological studies are an efficient way to analyze the results of unplanned experiments.

In 1996, I read that Japanese-American men living in Hawaii had two and a half times the prevalence of  Alzheimer’s disease as native Japanese. I knew that AD patients often had higher concentrations of aluminum in their brains than other people, and that acid rain increased the concentration of aluminum in trees. It quickly occurred to me that the American diet must be the cause of the increased AD rate, and that by using the ecological approach, I could prove it. My first study, published in 1997, compared AD prevalence rates for 11 countries with macro-dietary factors of national diets. Total fat was found to have the highest correlation with AD, followed by total energy (calories), with fish reducing risk slightly, while countries such as China, Japan, and India, with large amounts of rice in the diet, had very low  Alzheimer’s disease rates. This study was the first major study linking diet to risk of AD and led to observational studies that confirmed the findings five years later.

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Formal Education May Reduce Alzheimer’s Risk By Building Stronger Brain Connections

MedicalResearch.com Interview with:

Auriel Willette, PhD Assistant Professor Departments of Food Science and Human Nutrition, and Psychology Iowa State Universit

Dr. Auriel Willette

Auriel Willette, PhD
Assistant Professor
Departments of Food Science and Human Nutrition, and Psychology
Iowa State University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Alzheimer’s disease (AD) field continues to look for biological markers that can detect onset and progression of the disease, mainly memory decline and atrophy of medial temporal lobe where conscious memories are formed. The immune system has long been known to affect the onset and progression of Alzheimer’s disease (AD), usually through a process called inflammation in the brain that causes damage to brain cells called neurons. We wished to examine all available immune system data in a large, well-established cohort across the AD spectrum and discover which immune markers best explained memory decline and medial temporal atrophy over 2 years.

In essence, among dozens of candidate immune markers, we consistently found two to be most relevant: neuronal pentraxin 2 (NPTX2) and chitinase-3-like-protein-1 (C3LP1). NPTX2 is important for facilitating communication between neurons, whereas C3LP1 is related to activation of a part of the immune system that causes inflammation in the brain. To our surprise, higher NPTX2 levels at baseline were potently related to less memory loss and less medial temporal atrophy over 2 years. C3LP1, by contrast, was a relatively poor predictor. NPTX2 also better predicted levels of amyloid and tau in the brain, which are generally thought to help cause AD.

Finally, we found that more years of education led to higher NPTX2 levels, suggesting that more formal learning leads to more stable, stronger connections between neurons that give rise to memory.

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Analysis of Multiple MRI and PET Images Detects Earliest Signs of Alzheimer’s Disease

MedicalResearch.com Interview with:

Dr. Yasser Iturria Medina PhD Post-doctoral fellow Montreal Neurological Institute

Dr. Y. M. Medina

Dr. Yasser Iturria Medina PhD
Post-doctoral fellow
Montreal Neurological Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We used over 200 peripheral molecular biomarkers, five different neuroimaging modalities and cognitive/clinical measurements to detect spatiotemporal abnormalities in subjects with dementia or with mild signs of cognitive deterioration. By means of a mathematical framework, we reordered all the biomarkers/descriptors considered, according to how much they change during the disease process. The results suggested that, contrary as suggested by more traditional clinical analyses, there are multiple early signs of neurodegeneration, at the molecular level and at the brain’s macroscopic and cognitive state. In particular, we observed notable early signs of generalized vascular dysregulation, which may be supporting the vascular hypothesis of Alzheimer’s disease. However, we still need to perform deeper analyzes, in order to clarify the complex causal mechanisms that trigger the disease.

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Promising Study Evaluates Chemotherapy for Parkinson’s and Lewy Body Dementia

MedicalResearch.com Interview with:

Charbel Moussa MD. PhD Assistant Professor of Neurology Director- Laboratory for Dementia and Parkinsonism Clinical Research Director- National Parkinson's Foundation Center for Excellence Translational Neurotherapeutics Program Department of Neurology Georgetown University Medical Center Washington DC.

Dr. Charbel Moussa

Charbel Moussa MD. PhD
Assistant Professor of Neurology
Director- Laboratory for Dementia and Parkinsonism
Clinical Research Director- National Parkinson’s Foundation Center for Excellence
Translational Neurotherapeutics Program
Department of Neurology
Georgetown University Medical Center
Washington DC.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We conducted a pilot open label proof-of-concept study to evaluate the safety and tolerability of Nilotinib in participants with advanced Parkinson’s disease (PD) with dementia (PDD) or dementia with Lewy bodies (DLB). Our primary objective is to demonstrate that low oral daily doses of 150mg or 300mg Nilotinib (compared to 600-800mg in cancer) are safe and tolerated.

Our secondary objectives are that Nilotinib will cross the blood brain barier and may inhibit cerebral spinal fluid Abl. Based on preclinical data we also hypothesized that Nilotinib will increase DA levels. Motor and cognitive functions were also measured as exploratory clinical outcomes. Other exploratory outcomes are that Nilotinib may alter PD-related CSF biomarkers DJ-1 and α-synuclein. As most participants in this study had dementia we also explored the effects of Nilotinib on Alzheimer’s Disease-related CSF biomarkers, including Aβ40 and Aβ42, total tau and phosphorylated tau (p-tau).

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Patients with Dementia Incur Higher Health Care Costs Even Before Diagnosis

MedicalResearch.com Interview with:

Pei-Jung Lin, Ph.D. Assistant Professor Center for the Evaluation of Value and Risk in Health Institute for Clinical Research and Health Policy Studies Tufts Medical Center Boston, MA 02111

Dr. Pei-Jung Lin

Pei-Jung Lin, Ph.D.
Assistant Professor
Center for the Evaluation of Value and Risk in Health
Institute for Clinical Research and Health Policy Studies
Tufts Medical Center
Boston, MA 02111

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Alzheimer’s disease (AD) is a slow, progressive disease. Many people with AD may live for years with the disease left unrecognized or untreated, in part because the early symptoms are mild and often mistaken as part of normal aging. In this study, we found that Alzheimer’s patients may use more health care services and incur higher costs than those without dementia even before they receive a formal diagnosis. For example, total Medicare expenditures were 42% higher among Alzheimer’s patients than matched controls during the year prior to diagnosis ($15,091 vs. $10,622), and 192% higher in the first year immediately following diagnosis ($27,126 vs. $9,274). We also found similar trends among Medicare patients with mild cognitive impairment (MCI)— a prodromal stage of AD and associated with higher dementia risk.

Our study suggests that an Alzheimer’s disease or MCI diagnosis appears to be prompted by other health problems such as cardiovascular and cerebrovascular diseases, pneumonia, renal failure, urinary tract infections, and blood and respiratory infections. This finding likely reflects a failure of ambulatory care related to the impact of cognitive impairment on other chronic conditions.

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Could Alzheimer’s Disease Patients Benefit From Anti-Platelet Therapy?

MedicalResearch.com Interview with:

Prof. Margitta Elvers, PhD Institute of Hemostasis, Hemotherapy and Transfusion Medicine University Clinic of the Heinrich-Heine-University Düsseldorf Düsseldorf Germany

Prof. Margitta Elvers

Prof. Margitta Elvers, PhD
Institute of Hemostasis, Hemotherapy and Transfusion Medicine
University Clinic of the Heinrich-Heine-University Düsseldorf
Düsseldorf Germany

MedicalResearch.com: What is the background for this study? What are the main findings?

Prof. Elvers: Platelets are the main players in hemostasis and thrombosis, but are also recognized to be involved in the pathology of different neurodegenerative diseases. It is well known that amyloid-beta is able to activate platelets and to induce platelet activation. In Alzheimer’s Disease (AD) patients, platelet activation is enhanced and a correlation between AD and vascular diseases such as stroke and atherosclerosis was shown in different studies However, a direct contribution of platelets to the progression of Alzheimer’s disease (AD) was an open question for many years. In the last years our group in Düsseldorf, Germany, provided strong evidence for platelets to play a relevant role in the progression of AD, because AD transgenic mice showed enhanced platelet signaling that translated into almost unlimited thrombus formation in vitro and accelerated carotid artery occlusion in vivo suggesting that these mice are at high risk of arterial thrombosis leading to cerebrovascular and unexpectedly to cardiovascular complications that might be also relevant in AD patients. In the recent study, we analyzed the contribution of platelets, which accumulate at vascular Abeta deposits, to cerebral amyloid angiopathy (CAA), a vascular dysfunction in most of  Alzheimer’s disease patients, characterized by deposits of Abeta in the wall of cerebral vessels. We found that synthetic monomeric Abeta is able to bind to integrin alphaIIbbeta3 via its RHDS (Arg-His-Asp-Ser) sequence thereby stimulating the release of adenosine diphosphate (ADP) and clusterin from platelets. ADP enhanced integrin activation via the ADP receptors P2Y1 and P2Y12 and further increased platelet clusterin release and Abeta fibril formation. Clopidogrel, an antiplatelet drug which irreversible inhibits P2Y12, inhibited Abeta aggregation in human and murine platelet cell cultures. Treatment of AD transgenic mice with clopidogrel for three months reduced clusterin plasma levels and the incidence of CAA.

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ALS Drug May Reverse Some Age-Related Cognitive Decline

MedicalResearch.com Interview with:
Ana Pereira, MD
Instructor in Clinical Medicine

Bruce McEwen’s laboratory
Rockefeller University 

MedicalResearch.com: What is the background for this study?

Dr. Pereira: The neurons most susceptible to dying in Alzheimer’s disease are the ones that use glutamate as a neurotransmitter (chemical messengers that enable neurotransmission). Glutamate is the major excitatory neurotransmitter in the brain and its regulation is critical for learning and memory.

When glutamate is not located in the correct place and amount, it causes several deleterious effects to neurons that can ultimately lead to cell death. Importantly, the glutamate transporter EAAT2 is the dominant regulator of glutamate levels and it is highly depressed in Alzheimer’s disease. Furthermore, glutamatergic dysregulation is implicated in several pathological mechanisms in Alzheimer’s disease including the release and toxicities of the proteins implicated in Alzheimer’s disease: amyloid-beta (which form amyloid plaques) and tau (which form neurofibrillary tangles).

Better regulation of glutamatergic neural circuits is critically important to effectively treat age-related cognitive decline and Alzheimer’s disease.

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Relationship Between Plasma Aβ Levels, Cognitive Function and Brain Volumetrics

MedicalResearch.com Interview with:

Dr Anne Poljak Leader of the Proteomics Group Centre for Healthy Brain Ageing (CHeBA) UNSW, Australia

Dr. Anne Poljak

Dr Anne Poljak
Leader of the Proteomics Group
Centre for Healthy Brain Ageing (CHeBA)
UNSW, Australia 

MedicalResearch.com: What is the background for this study? 

Dr Poljak: Amyloid-beta (Aβ) peptides are found in abundance in the plaque particles which build up in the Alzheimer’s brain and small blood vessels of the brain, and are therefore considered hallmark features of Alzheimer’s disease. However they are also found in blood which is a convenient body fluid for sampling purposes. We therefore wished to assay them in plasma samples from one of our longitudinal population based studies of older age individuals (70 – 90 years) – the Centre for Healthy Brain Ageing’s Sydney Memory and Ageing Study.

Other research groups had previously measured these peptides in plasma, but there was controversy in the area because of differences in outcomes across laboratories. So one of the main questions was whether plasma levels of Aβ peptides have any relationship with what is happening in the brain, or are they a red-herring? We wanted to see how the levels we found would compare with the findings of others in relation to Alzheimer’s disease and mild cognitive impairment. A further question was how our plasma levels would relate to other clinical measures including cognition and brain volumetrics. One of the precautions we took was to use an assay kit with very well characterized antibodies, so we could be confident that our method was specific for the two full length Aβ peptides (Ab1-40 and Ab1-42).

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Study Shows Shared Genetic Risks for Alzheimer’s and Autoimmune Disease

MedicalResearch.com Interview with:

Jennifer S. Yokoyama, PhD Assistant Professor, Memory and Aging Center University of California, San Francisco

Dr. Yokoyama

Jennifer S. Yokoyama, PhD
Assistant Professor, Memory and Aging Center
University of California, San Francisco

MedicalResearch.com: What is the background for this study?

Dr. Yokoyama: Alzheimer’s disease is a common neurodegenerative disease that occurs in older adults. Clinically, Alzheimer’s disease is primarily associated with changes in cognition (e.g., declines in memory, language and visuospatial functioning). Pathologically, Alzheimer’s disease is associated with misfolded amyloid beta and tau proteins and can only be definitively diagnosed at autopsy. It has long been appreciated that there is a link between the immune system and Alzheimer’s disease, and there are multiple sources of evidence that suggest that immune activity may be increased in patients with Alzheimer’s. Although there is strong evidence for an association between immune activity and Alzheimer’s disease there has always been a chicken-egg problem because we don’t know whether the Alzheimer’s disease process triggers the immune response or whether altered immune function promotes the Alzheimer’s disease process.

Genetic information can offer important clues about the role of the immune system in Alzheimer’s disease. Each person has a unique genetic fingerprint, and different combinations of gene changes (“variants”) put individuals at higher or lower risk for different diseases. Genetic data enables us to test whether having a certain genetic variant puts people at greater risk for both Alzheimer’s disease and autoimmune diseases, immune system diseases in which the immune system is overactive (e.g., Crohn’s disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, Celiac’s disease, and psoriasis). Rather than only responding to foreign objects such as bacteria and viruses, in autoimmune diseases the immune system also responds to the body’s own material, which do not ordinarily create an immune response, thereby leading to symptoms associated with higher levels of inflammation and other long-term problems. A variant that increases risk for both Alzheimer’s disease and autoimmune diseases would suggest a common biological pathway.

MedicalResearch.com: What are the main findings?

Dr. Yokoyama: In our study we tested whether there are genetic variants that put people at increased risk for both Alzheimer’s disease and autoimmune diseases. We found eight genetic variants that influence people’s risk for both Alzheimer’s disease and autoimmune disease. Some of these variants were associated with lower risk of autoimmune disease and Alzheimer’s disease, but two variants were associated with greater risk for both.   Continue reading

Why Does Alzheimer’s Take Away Ability To Recognize Faces?

MedicalResearch.com Interview with:

Dr. Sven Joubert, PhD Département de psychologie, Université de Montréal Centre de recherche Institut universitaire de gériatrie de Montréal (CRIUGM) Montréal, Canada

Dr. Sven Joubert

Dr. Sven Joubert, PhD
Département de psychologie, Université de Montréal
Centre de recherche Institut universitaire de gériatrie de Montréal (CRIUGM)
Montréal, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Joubert: Difficulties in recognizing familiar people in Alzheimer’s disease have typically been attributed to the underlying memory impairment. There is evidence however that people with Alzheimer’s disease also have difficulties in visual perception. The aim of this study was to determine if people with Alzheimer’s were specifically impaired at face perception. In the current study, people with Alzheimer’s along with healthy seniors were asked to process pictures of faces and cars at both upright and inverted orientation. Results showed that persons with Alzheimer’s disease had a reduced face inversion effect, in other words they had a disproportionate impairment in processing upright relative to inverted faces. This reduced inversion effect in Alzheimer’s disease, which was specific to faces, may reflect a reduced ability in “holistic” processing of faces, in other words the ability to form intergrated and individualized representations of faces based on their local features.

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Just One Seafood Meal Per Week Linked To Lower Risk of Alzheimer’s Disease

MedicalResearch.com Interview with:

Dr. Martha Clare Morris ScD Section on Nutrition and Nutritional Epidemiology Department of Internal Medicine Rush University Medical Center Chicago, Illinois

Dr. Martha Morris

Dr. Martha Clare Morris ScD
Section on Nutrition and Nutritional Epidemiology
Department of Internal Medicine
Rush University Medical Center
Chicago, Illinois

Medical Research: What is the background for this study? What are the main findings?

Dr. Morris: We examined seafood consumption in a cohort of older residents of the city of Chicago and related their diets to neuropathologies associated with dementia in 286 brains of the participants when they died.  We also examined the brain tissue for mercury levels.  We found that seafood consumption of 1 or more per week was associated with less Alzheimer disease neuropathologies.  Higher seafood consumption was also associated with more mercury levels in the brain but increased mercury levels were not associated with Alzheimer’s Disease or other brain neuropathologies.

Medical Research: What should clinicians and patients take away from your report?

Dr. Morris: This study supports previous investigations showing that just one seafood meal per week is associated with less risk of Alzheimer’s Disease dementia.  The current study also allays concerns that the possibility of increased consumption of mercury from moderate seafood consumption will be harmful.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Morris: Future research should examine other potential harmful effects of mercury exposure to the brain- for example, effects on synaptic proteins or neurons in the brain

Citation:

Morris M, Brockman J, Schneider JA, et al. Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults.JAMA. 2016;315(5):489-497. doi:10.1001/jama.2015.19451.

Dr. Martha Clare Morris ScD (2016). Just One Seafood Meal Per Week Linked To Lower Risk of Alzheimer’s Disease 

Some Blood Pressure Medications May Be Protective Against Alzheimer’s Disease

MedicalResearch.com Interview with:
Dr. Juan M. Saavedra, MD and
Dr. Abdel Elkahloun PhD
Comparative genomics and Cancer Genetics Branch
National Human Genome Research Institute,
National Institutes of Health, Bethesda, MD

MedicalResearch: What is the background for this study? What are the main findings?

Response: Alzheimer’s disease is the most frequent age-related dementia, a progressing, devastating illness without effective treatment. By the time it is diagnosed, major and irreversible cell injury has already occurred. It is therefore imperative to identify therapeutic agents effective against early, pre-symptomatic injury mechanisms and risk factors increasing vulnerability the disease.

We focused on a class of compounds blocking receptors for Angiotensin II, the Angiotensin Receptor Blockers (ARBs). These compounds are commonly used for the treatment of hypertension, a major risk factor for Alzheimer’s disease.

We and others have found that in addition to their cardiovascular benefits, ARBs are strongly neuroprotective. The present study was designed to explore in depth the neuroprotective effects of one member of the ARB class, candesartan. To this effect we cultured neurons extracted from the rat brain. These neurons were exposed to high concentrations of glutamate, a recently identified early injury mechanism in Alzheimer’s disease. We found that candesartan prevented glutamate-induced neuronal injury.

We conducted in-depth examination of our results by genome-wide expression profile analysis. We found that candesartan normalized glutamate-induced alterations in expression of hundreds of genes, including many involved in neuronal inflammation, cardiovascular disease, diabetes and alterations in amyloid metabolism a hallmark for Alzheimer’s disease. This was evidence of direct neuroprotective effects of relevance for this disorder.

When we compared our results with published databases obtained from autopsy samples from Alzheimer’s disease patients, we found impressive correlations. The expression of more than 400 genes altered by glutamate and normalized by candesartan in our cultures was similarly changed in the Alzheimer’s databases.

The conclusion was that our cell culture results represented alterations found in the human condition. Our observations provide novel evidence of neuroprotection from early mechanisms of injury in Alzheimer’s disease and support testing candesartan in controlled clinical studies including individuals at the early stages of the illness, to unequivocally demonstrate their therapeutic effect.

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Moderate Alcohol Use Linked To Lower Mortality in Alzheimer’s Disease

MedicalResearch.com Interview with:

Chia-Yu Chu

Dr. Frans Boch Waldorff

Professor, Frans Boch Waldorff
General Practitioner
Research Unit of General Practice
Denmark

MedicalResearch: What is the background for this study? What are the main findings?

Prof. Waldorff: While there are numerous studies focusing on alcohol as a risk factor for dementia and mortality in healthy subjects, virtually no attention has been paid to the effect of alcohol consumption in patients with Alzheimer’s disease (AD). Considering that AD is a neurodegenerative disorder and that alcohol has known neurotoxic effects, one could easily jump to the conclusion that alcohol is damaging for patients with AD. The aim of this study was to investigate whether the positive association between moderate alcohol intake and mortality shown in population-based studies on healthy subjects can be transferred to patients with mild AD.

In our study we found that patients with mild  Alzheimer’s disease , moderate alcohol consumption (two to three units per day) was associated with a significantly lower risk of death compared with those who only had alcohol occasionally (one or less than one unit per day), and with those who had high alcohol intake (more than 3 units per day). Abstinence or high alcohol intake did not significantly raise mortality compared with those drinking only occasionally.

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Androgen Deprivation Therapy May Raise Risk of Alzheimer’s Disease

Kevin T. Nead, MD, MPhil Dept. of Radiation Oncology Perelman School of Medicine University of Pennsylvania

Dr. Kevin Nead

MedicalResearch.com Interview with:
Kevin T. Nead, MD, MPhil
Dept. of Radiation Oncology
Perelman School of Medicine
University of Pennsylvania

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Nead: There are a growing number of studies suggesting that the use of  Androgen Deprivation Therapy (ADT)  may be associated with cognitive changes and some of these changes overlap with characteristic features of Alzheimer’s disease. In addition, low testosterone levels have been associated with Alzheimer’s disease risk and ADT lowers testosterone levels. Despite these findings, we could not identify any studies examining the association between ADT and Alzheimer’s disease risk. We therefore felt this study could make an important contribution in guiding future research to fully understand the relative risks and benefits of ADT.

We examined electronic medical record data from Stanford University and Mt. Sinai hospitals to identify a cohort of 16,888 patients with prostate cancer. We found that men with prostate cancer who received Androgen Deprivation Therapy were more likely to develop Alzheimer’s disease than men who did not receive  Androgen Deprivation Therapy. We also found that this risk increased with a longer duration of ADT. These results were consistent using multiple statistical approaches and separately at both Stanford and Mr. Sinai.

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BRCA1 Depletion in Nerve Cells Contributes To Cognitive Decline in Alzheimer’s disease

Elsa Suberbielle, DVM, PhD Research Scientist Gladstone Institute of Neurological Diseases San Francisco, CA 94158

Dr. Elsa Suberbielle

MedicalResearch.com Interview with:
Elsa Suberbielle, DVM, PhD
Research Scientist
Gladstone Institute of Neurological Diseases
San Francisco, CA 94158

Medical Research: What is the background for this study?

Dr. Suberbielle: BRCA1 is a key protein involved in DNA repair, and mutations that impair its function increase the risk for breast and ovarian cancer. Research into DNA repair mechanisms in dividing cells recently was recently rewarded by the Nobel Prize in Chemistry. In such cells, BRCA1 helps repair a type of DNA damage known as double-strand breaks that can occur when cells are injured. In neurons, though, such breaks can occur even under normal circumstances, for example, after increased brain activity, as shown by the team of Gladstone scientists in an earlier study. The researchers speculated that in brain cells, cycles of DNA damage and repair facilitate learning and memory, whereas an imbalance between damage and repair disrupts these functions.

Medical Research: What are the main findings?

Dr. Suberbielle In a new study published in Nature Communications, Researchers from the Gladstone Institutes demonstrates that Alzheimer’s disease is associated with a depletion of BRCA1 in neurons and that BRCA1 depletion can cause cognitive deficits.

The researchers experimentally reduced BRCA1 levels in the neurons of mice. Reduction of the DNA repair factor led to an accumulation of DNA damage and to neuronal shrinkage. It also caused learning and memory deficits. Because Alzheimer’s disease is associated with similar neuronal and cognitive problems, the scientists wondered whether they might be mediated by depletion of BRCA1. They therefore analyzed neuronal BRCA1 levels in post-mortem brains of Alzheimer’s patients.

Compared with non-demented controls, neuronal BRCA1 levels in the patients were reduced by 65-75%. To determine the causes of this depletion, the investigators treated neurons grown in cell culture with amyloid-beta proteins, which accumulate in Alzheimer brains. These proteins depleted BRCA1 in the cultured neurons, suggesting that they may be an important cause of the faulty DNA repair seen in Alzheimer brains. Further supporting this conclusion, the researchers demonstrated that accumulation of amyloid-beta in the brains of mice also reduced neuronal BRCA1 levels. They are now testing whether increasing BRCA1 levels in these mouse models can prevent or reverse neurodegeneration and memory problems.

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New Drug Combination Studied To Treat Agitation in Alzheimer’s Disease

Jeffrey L. Cummings, M.D., Sc.D. Director, Lou Ruvo Center for Brain Health Camille and Larry Ruvo Chair for Brain Health Cleveland Clinic Las Vegas, NV 89106MedicalResearch.com Interview with:
Jeffrey L. Cummings, M.D., Sc.D.
Director, Lou Ruvo Center for Brain Health
Camille and Larry Ruvo Chair for Brain Health
Cleveland Clinic  Las Vegas, NV 89106 

Medical Research: What is the background for this study? What are the main findings?

Dr. Cummings: Agitation is a common problem in Alzheimer’s disease (AD); approximately 70% of patients with AD will experience periods of agitation.  This difficult behavior challenges patients and caregivers, adversely affects quality of life, and may precipitate institutionalization.  There are not drugs approved for treatment of agitation in Alzheimer’s disease.

The study reported in JAMA showed that a drug based on a combination of dextromethorphan and quinidine (DM/Q) produced statistically significant and clinically meaningful reduction in agitation in Alzheimer’s disease patients.  The study met its primary outcome (decline in the Neuropsychiatric Inventory agitation scale in drug compared to placebo) and many of its secondary outcomes (e.g, decreases in caregiver stress).  The agent was safe and well tolerated.

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Several Modifiable Risk Factors for Alzheimer’s Disease Identified

Jin-Tai Yu MD, PhD Memory and Aging Center, Department of Neurology University of California San Francisco San Francisco, CA 94158
MedicalResearch.com Interview with:
Jin-Tai Yu MD, PhD
Memory and Aging Center,
Department of Neurology
University of California San Francisco
San Francisco, CA 94158

Medical Research: What is the background for this study? What are the main findings?

Response: The number of dementia cases in the whole world was estimated to be 35.6 million in 2010 and this number was expected to almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050. The global prevalence of dementia was 5-7% and Alzheimer’s disease accounts for roughly 60%. This data means that we are facing an increasing number of global populations of this specific neurodegenerative disease and also the heavy burden brought by it.

Data from the website of global clinical trials (http://clinicalTrials.gov) showed that a total of 1,732 clinical trials for Alzheimer’s disease were under way. However, the previous results are not so optimistic, possibly due to the complex etiological mechanisms. In one word, we had currently no effective drugs for this disease. Figuring out how to effectively prevent its occurrence is increasingly attracting people’s attentions.Therefore, we have done the most extensive and comprehensive systematic review and meta-analysis to date, which employs a full-scale search of observational studies to calculate effect sizes and grade the evidence strength of various modifiable risk factors for this disease. We hope these results will be informative and instructive.

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Insulin Resistance Linked To Poor Verbal Fluency in Women

Laura Ekblad, MD, researcher Turku PET CentreMedicalResearch.com Interview with:
Laura Ekblad, MD, researcher
Turku PET Centre

Medical Research: What is the background for this study? What are the main findings?

Dr. Ekblad: The background for our study is that the metabolic syndrome and diabetes have been shown to increase the risk for cognitive decline and dementia. Also, insulin resistance is thought to play a pivotal role in the pathophysiology of Alzheimer´s disease. In addition, intranasal insulin administration is being studied as a promising treatment for Alzheimer´s disease. Previous studies indicate that both gender and APOE epsilon 4 genotype modulate the effects of insulin on cognition.

Our main findings are that insulin resistance is associated with poorer verbal fluency, but only in women. Our population-based study consisted of adults from 30-97 years of age and we had nearly 6000 participants. Age did not modulate the association of insulin resistance and cognition, which means that our results apply even to young adults. We also found that insulin resistance associated with poorer verbal fluency only in non-carriers of the APOE epsilon 4 genotype.

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Accurate Diagnosis of Alzheimer’s Disease Can Save Money and Resources

Noam Y. Kirson, Ph.D.  Vice President Analysis Group, Inc. Economic, Financial, and Strategy Consulting Boston, MA 02199MedicalResearch.com Interview with:
Noam Y. Kirson, Ph.D. 
Vice President Analysis Group, Inc.
Economic, Financial, and Strategy Consulting
Boston, MA 02199

Medical Research: What is the background for this study? What are the main findings?

Dr. Kirson: Developments in diagnostic technology now support ruling out Alzheimer’s disease (AD) among patients presenting with symptoms of cognitive decline, possibly facilitating earlier and more accurate diagnosis of non-Alzheimer’s dementias. Our study assessed potential economic benefits of timely rule out of Alzheimer’s disease among U.S. Medicare beneficiaries eventually diagnosed with vascular dementia (VD) or Parkinson’s disease (PD) by estimating excess medical costs among those previously misdiagnosed withAlzheimer’s. We found that approximately one in six beneficiaries with VD and one in twelve beneficiaries with PD had a prior Alzheimer’s disease diagnosis. Further, we found that VD and PD patients previously diagnosed with Alzheimer’s disease incurred substantially higher medical costs in periods leading up to and including their VD/PD diagnoses, compared with matched counterparts with no prior AD diagnosis during the same timeframe. Perhaps most interestingly, excess costs declined – and eventually dissipated – following the confirmed VD/PD diagnoses.

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Insulin Resistance Linked to Poor Memory Performance

Auriel A. Willette, M.S., Ph.D. Food Science and Human Nutrition Neuroscience Interdepartmental Graduate Program Gerontology Interdepartmental Graduate Program Iowa State University, AmesMedicalResearch.com Interview with:
Auriel A. Willette, M.S., Ph.D.
Food Science and Human Nutrition
Neuroscience Interdepartmental Graduate Program
Gerontology Interdepartmental Graduate Program
Iowa State University, Ames

Medical Research: What is the background for this study? What are the main findings?

Response: Obesity is a major health concern around the world. Obesity causes insulin resistance, defined in this case as the inability of insulin to bind to its receptor and mediate glucose metabolism. Other researchers and I have recently found that higher insulin resistance is associated with less glucose metabolism in the brains of patients with Alzheimer’s disease. This relationship is found primarily in medial temporal lobe, an area necessary for generating new memories of facts and events. This is important because Alzheimer’s disease is characterized by progressive decreases in glucose metabolism over time, and partly drives worse memory performance. Insulin resistance in midlife also increases the risk of developing Alzheimer’s disease.

We wanted to determine if insulin resistance is linked to similar effects in cognitively normal, late middle-aged participants decades before Alzheimer’s disease typically occurs. If so, insulin resistance might be an important biological marker to track from middle-age onwards. Thus, we examined the association between insulin resistance, regional glucose metabolism using FDG-PET, and memory function in 150 middle-aged participants, many of whom had a mother or father with Alzheimer’s disease.

We found that higher insulin resistance was strongly associated with less glucose metabolism throughout many brain regions, predominantly in areas that are affected by Alzheimer’s disease. The strongest statistical effects were found in left medial temporal lobe, which again is important for generating new memories. This relationship, in turn, predicted worse memory performance, both immediately after learning a list of words and a 20-minute delay thereafter.

The take-home message is that insulin resistance has an Alzheimer’s-like association with glucose metabolism in middle-aged, cognitively normal people at risk for Alzheimer’s, an association which is related to worse memory.

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Precision Antibodies Target Defective Protein in Alzheimer’s and Parkinson’s Model

Fernando Goni, PhD MS Adjunct associate professor Department of Neurology, Center for Cognitive Neurology NYU School of Medicine NYU Langone Medical CenterMedicalResearch.com Interview with:
Fernando Goni, PhD MS
Adjunct associate professor
Department of Neurology, Center for Cognitive Neurology
NYU School of Medicine
NYU Langone Medical Center

Medical Research: What is the background for this study? What are the main findings?

Dr. Goni: It has been established that most neurodegenerative diseases including Alzheimer’s, Lewy Body and other dementias, Parkinson’s and prion diseases develop and progress along similar paths. In each disease, a particular protein undergoes a change in its shape from a soluble, physiologically functional protein to a protein that has lost the ability to perform its required tasks in the brain, starting off a chain reaction of binding to each other with little control. These aggregates become toxic to brain cells.

We raised antibodies in mice against the common beta-sheet structures present in toxic oligomers of many neurodegenerative diseases including amyloid and tau in Alzheimer’s; oligomeric forms of prions and oligomerized alpha-synuclein in Parkinson‘s. From that response, we produced monoclonal antibodies of the same characteristics.

At least three of the monoclonals recognize pathological structures in histological samples of human brains from Alzheimer’s disease, Parkinson’s disease and GSS (human prionosis). They also recognized in vitro the oligomeric forms particular for each disease.

In old animals of a mouse model of Alzheimer’s, that already had pathology, the monoclonal antibodies could rescue behavior and reduced significantly the oligomers of Tau and Abeta. Continue reading

PET Scan Can Detect Amyloid In Alzheimer’s and Other Dementias

Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging CenterMedicalResearch.com Interview with:
Rik Ossenkoppele PhD.
Postdoctoral researcher
UCSF Memory and Aging Center

MedicalResearch: What is the background for this study?

Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database.

MedicalResearch: What are the main findings?

Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of
1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype),
2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and
3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”).
The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials.

In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect
1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or
2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander.

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Low Dose Seizure Medication May Benefit Early Alzheimer’s Disease

Arnold Bakker, Ph.D. Assistant Professor Division of Psychiatric Neuroimaging Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine Baltimore, MD 21287MedicalResearch.com Interview with:
Arnold Bakker, Ph.D. Assistant Professor
Division of Psychiatric Neuroimaging
Department of Psychiatry and Behavioral Sciences
The Johns Hopkins University School of Medicine
Baltimore, MD 21287

Medical Research: What is the background for this study? What are the main findings?

Dr. Bakker: Patients who are at increased risk for developing dementia due to Alzheimer’s disease show hyperactivity in an area of the brain called the hippocampus, which is critically important for memory function. This study investigated the functional significance of this hyperactivity and determined if, similar to animal studies, treatment with low dose levetiracetam would reduce this increased activation and improve memory function in these patients. Results showed that this overactivity is a dysfunctional condition that contributes to the memory impairment such that treatment with very low doses of levetiracetam both reduces this overactivity and improves memory function in these patients.
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Lifestyle Factors May Limit Cognitive Decline

MedicalResearch.com Interview with:
Miia Kivipelto MD, PhD, Professor
Deputy Head, Senior Geriatrician
Aging Research Center and Alzheimer Disease Research Center
Karolinska Institutet Clinical Trials Unit, Memory Clinic
Karolinska University Hospital Stockholm, Sweden

Medical Research: What is the background for this study? What are the main findings?

Dr. Kivipelto: Epidemiological studies have linked several modifiable risk factors to cognitive impairment and dementia but evidence from randomized controlled trials (RCT) has been lacking showing the efficacy of the interventions. Because cognitive impairment, dementia and Alzheimer’s disease are complex, multi-factorial disorders, multidomain interventions targeting several risk factors and disease mechanisms simultaneously could be needed for optimum preventive effect. The FINGER study is the first large, long-term RCT indicating that multi-domain intervention can improve and maintain cognitive functioning in at risk elderly people from the general population. We observed a significant intervention effects on the primary outcome (overall cognition), main secondary outcomes (executive functioning and processing speed) as well as on complex memory tasks and risk of cognitive decline. The multidomain lifestyle intervention was feasible and safe.

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Cognitive Function Test Helps Predict Future Memory Loss

Dr. Rebecca E. Amariglio Ph.D. Massachusetts Alzheimers Disease Research Center Massachusetts General HospitalMedicalResearch.com Interview with:
Dr. Rebecca E. Amariglio Ph.D.
Massachusetts Alzheimers Disease Research Center
Massachusetts General Hospital

Medical Research: What is the background for this study? What are the main findings?

Dr. Amariglio: As the field of Alzheimer’s disease moves towards early detection and treatment, new tests that can measure very subtle changes in cognitive functioning are needed. A new instrument developed by the Alzheimer’s Disease Cooperative Study that measures subjective report of memory changes of both the study participant and a study partner (usually a family member) was associated with cognitive decline over four years.  Specifically, greater report of memory concerns was associated with worse memory performance over time.
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MAPT locus on Chromosome 17 Links Parkinson’s and Alzheimer’s Diseases

Dr. Rahul S. Desikan MD, PhD Department of Radiologoy University of California, San Diego School of MedicineMedicalResearch.com Interview with:
Dr. Rahul S. Desikan MD, PhD
Department of Radiologoy
University of California, San Diego School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Desikan: The MAPT gene encodes the tau protein, which plays an integral role in Alzheimer’s disease (AD) neurodegeneration. Though a number of studies have investigated this issue, the role of the MAPT gene in Alzheimer’s disease is still unclear. In contrast, a number of studies have found a robust association between MAPT and increased risk for other ‘tauopathies’ like Parkinson’s disease (PD). In our study, rather than evaluating all possible genetic loci, we only assessed shared genetic variants between Alzheimer’s disease and PD. By using this type of approach, we were able to increase our statistical power for gene discovery in Alzheimer’s disease.

We found genetic overlap between Alzheimer’s disease and Parkinson’s disease at a locus on chromosome 17 within the MAPT region. Our findings demonstrate that this MAPT associated locus increases risk for Alzheimer’s disease, correlates with gene expression of MAPT and is associated with brain atrophy of the entorhinal cortex and hippocampus on longitudinal MRI scans.

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Brain’s Protective Blood Barrier Becomes Leaky With Age

MedicalResearch.com Interview with:
V. Zlokovic, MD, PhD Professor and Chair Department of Physiology and Biophysics Keck School of Medicine of USC.
V. Zlokovic, MD, PhD
Professor and Chair
Department of Physiology and Biophysics
Keck School of Medicine of USC.

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Zlokovic: Our team used high-resolution imaging of the living human brain to show for the first time that the brain’s protective blood barrier becomes leaky with age, starting at the hippocampus, a critical learning and memory center that is damaged by Alzheimer’s disease.

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Obesity in Midlife Increases Risk of Dementia and Alzheimer’s Disease

Nicolas Cherbuin PhD ARC Future Fellow - Director of the NeuroImaging and Brain Lab Centre for Research on Ageing, Health and Wellbeing Research School of Population Health - College of Medicine Biology and Environment Australian National UniversityMedicalResearch.com Interview with:
Nicolas Cherbuin PhD

ARC Future Fellow – Director of the NeuroImaging and Brain Lab
Centre for Research on Ageing, Health and Wellbeing
Research School of Population Health – College of Medicine Biology and Environment
Australian National University

Medical Research: What is the background for this study? What are the main findings?

Dr. Cherbuin: A number of modifiable risk factors for cognitive aging dementia and Alzheimer’s disease have been identified with a high level of confidence by combining evidence from animal research and systematic reviews of the literature in humans that summarise the available findings without focusing on extreme findings that come about from time to time in research. One such risk factor is obesity for which we have previously conducted a systematic review (Anstey et al. 2011). This showed that obesity is associated with a two-fold increased risk of dementia and a 60% increased risk of Alzheimer’s disease. What was surprising is that this effect was only detectable for obesity in middle age but not old age. This might suggest that the obesity only has an adverse effects on brain health earlier in life and that this effect fades at older ages. This is unlikely because a number of animal studies have shown that the biological mechanisms linking obesity with brain pathology do not disappear with older age but in fact appear to increase. Moreover, human studies show that thinking abilities decline faster in obese individuals. An alternative explanation is that human epidemiological studies investigating this question in older individuals include participants who do not have clinical dementia but in whom the disease is developing. Since dementia and Alzheimer’s disease pathology is associated with weight loss it is possible that estimated effects in humans have been confounded by this issue. Another possible confounder is that older people tend to lose muscle mass (sarcopenia) this may lead to the paradoxical condition in aging where a person has a normal weight but has excessive fat mass. Since it is fat tissue that is linked to risk to cerebral health it may have led to the apparently contradictory findings that obesity may not be a risk in older age. It is therefore of great interest to clarify whether obesity in early old age in individuals free of dementia is associated with poorer cerebral health. The hippocampus is one of the structures most sensitive stressors. Because obesity is known to lead to a state of chronic inflammation which is deleterious to the hippocampus, it was a logical structure to investigate. Moreover, the hippocampus is needed for memory function and mood regulation and is directly implicated in the dementia disease process.

This study investigated 420 participants in their early 60s taking part in a larger longitudinal study of aging taking place in Canberra, Australia and who underwent up to three brain scans over an 8-year follow-up. These individuals were free of dementia and other neurological disorders. Associations between obesity and shrinkage of the hippocampus were investigated with longitudinal analyses which controlled for major confounders.

The main findings were that overweight and obese participants had smaller volume of the hippocampus at the start of the study. In addition, the hippocampus shrunk more in these individuals over the follow-up period.

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Study Enhances Understanding of Genetic Mechanisms of Memory

Vijay Ramanan, PhD Indiana University Center for Neuroimaging (CfN) Department of Radiology Indianapolis, IN 46202MedicalResearch.com Interview with:
Vijay Ramanan, PhD
Indiana University Center for Neuroimaging (CfN)
Department of Radiology
Indianapolis, IN 46202

Medical Research: What is the background for this study? What are the main findings?

Dr. Ramanan: Impairment in episodic memory is one of the first clinical deficits in early Alzheimer’s disease, the most common cause of dementia.  Among other examples, this might be reflected as an inability to recall an article recently read or as difficulty remembering what one had for dinner last night.  Unfortunately, the genetic and environmental mechanisms underlying these deficits are not fully understood.  Our goal was to discover new genes and pathways underlying memory performance to help identify potential drug targets for protecting against and ultimately reversing memory loss in dementia and normal aging.

Through studying a large representative sample of older Americans, we discovered a variant (single nucleotide polymorphism or SNP) in the FASTKD2 gene associated with better memory performance and replicated this finding in independent samples.  We then integrated additional data to extend our understanding of the effect of this SNP.  For example, we know that the hippocampus is a vital brain structure for encoding and retrieving memories and it is well-understood that decreased hippocampal volume is a key early marker of Alzheimer’s disease and one that can be measured noninvasively through magnetic resonance imaging (MRI).  We predicted that this new memory-protective SNP would be associated with increased hippocampal volume and this turned out to be true.  We also discovered that carriers of this memory-protective SNP exhibited lower levels of proteins involved in cell death in the cerebrospinal fluid bathing the brain and spinal cord, a striking finding given that FASTKD2 encodes a protein that appears to promote apoptosis (i.e., programmed cell death).  Together, these convergent findings are consistent with a neuroprotective effect of this novel SNP discovery.  More broadly, our results nominate FASTKD2 and its functional pathways as potential targets for modulating neurodegeneration to combat memory loss in older adults.

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Neurotic Symptoms In Midlife May Presage Alzheimer’s Dementia

Lena Johansson, PhD, MSc, RN Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry Sahlgrenska Academy at Gothenburg UniversityMedicalResearch.com Interview with:
Lena Johansson, PhD, MSc, RN
Institute of Neuroscience and Physiology
Department of Psychiatry and Neurochemistry
Sahlgrenska Academy at Gothenburg University


Medical Research: What are the main findings of the study?

Dr. Johansson: We found that a higher degree of neuroticism in midlife was associated with increased risk of Alzheimer’s disease over 38 years. On the 24 point scale, the risk increased with 4% per each step. Women who score high on the neuroticism scale were more likely to experience feelings such as anxiety, nervousness, worry, and irritability, and they were more moodiness and stress-prone.

The association between neuroticism and Alzheimer’s disease diminished after adjusting for longstanding perceived distress symptoms, which suggest that the associations was at least partly depended on long-standing distress symptoms.

When the two personality dimensions were combined, women with high neuroticism/low extraversion had a double risk of Alzheimer’s disease compared to those with low neuroticism/high extraversion.

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Long Term Benzodiazepines May Increase Alzheimer’s Disease Risk

Sophie Billioti de Gage PharmD University of Bordeaux Segalen FranceMedicalResearch.com Interview with:
Sophie Billioti de Gage PharmD
University of Bordeaux Segalen
France

 

Medical Research: What are the main findings of the study?

Answer: The risk of Alzheimer’s disease was found increased by 43-51% in persons (>65) having initiated a treatment with benzodiazepines in the past (>5 years before). Risk increased with the length of exposure and when long acting benzodiazepines were used.
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