Personality Changes Can Presage Cognitive Impairment

MedicalResearch.com Interview with:

Richard J. Caselli MD Department of Neurology Mayo Clinic Arizona Scottsdale, AZ 

Dr. Caselli

Richard J. Caselli MD
Department of Neurology
Mayo Clinic Arizona
Scottsdale, AZ  

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

Response: Personality changes are common in patients with a variety of dementing illnesses, and underlie the behavioral disturbances that complicate the course of dementia patients.  We have a been conducting a large longitudinal study of cognitive aging in individuals at genetically defined risk for Alzheimer’s disease (AD) based on their APOE genotype, and have been administering a large battery of neuropsychological tests as well as the gold standard personality questionnaire (the NEO-PI-R) in order to determine whether personality changes during the transition from normal cognition/preclinical AD to mild cognitive impairment.   Continue reading

High Rates of Amyloid Imaging Positivity in Patients With Primary Progressive Aphasia

MedicalResearch.com Interview with:

Miguel A. Santos-Santos, MD Department of Neurology, Memory and Aging Center University of California San Francisco Autonomous University of Barcelona, Cerdanyola del Valles, Spain

Dr. Miguel A. Santos-Santos

Miguel ASantosSantosMD
Department of Neurology, Memory and Aging Center
University of California San Francisco
Autonomous University of Barcelona, Cerdanyola del Valles, Spain

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

Response: Primary progressive aphasia (PPA) is a clinically and pathologically heterogeneous (generally Frontotemporal lobar degeneration [FTLD, generally tau or tdp proteinopathies] or Alzheimer’s disease [AD] pathology) condition in which language impairment is the predominant cause of functional impairment during the initial phases of disease. Classification of PPA cases into clinical-anatomical phenotypes is of great importance because they are linked to different prevalence of underlying pathology and prediction of this pathology during life is of critical importance due to the proximity of molecule-specific therapies. The 2011 international consensus diagnostic criteria established a classification scheme for the three most common variants (the semantic [svPPA], non-fluent/agrammatic [nfvPPA], and logopenic [lvPPA]) of PPA and represent a collective effort to increase comparability between studies and improve the reliability of clinicopathologic correlations compared to the previous semantic dementia and progressive non-fluent aphasia criteria included in the 1998 consensus FTLD clinical diagnostic criteria. Since their publication, a few studies have reported amyloid imaging and pathological results in PPA, however most of these studies are retrospective in nature and the prevalence of FTLD and Alzheimer’s disease pathological findings or biomarkers in each variant has been inconsistent across the literature, therefore prospective validation with biomarker and autopsy data remains scarce and highly necessary.
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Could Trace Levels of Lithium Protect Against 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 

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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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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