Alzheimer's - Dementia, Author Interviews, Mineral Metabolism / 19.12.2017

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.
Alzheimer's - Dementia, Author Interviews, BMJ, Education, Karolinski Institute / 10.12.2017

MedicalResearch.com Interview with:

[caption id="attachment_38832" align="alignleft" width="161"]Susanna C. Larsson, PhD Associate Professor, Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden Dr. Larsson[/caption]

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.

Alzheimer's - Dementia, Author Interviews, Mineral Metabolism / 07.12.2017

MedicalResearch.com Interview with: [caption id="attachment_38767" align="alignleft" width="128"]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[/caption] 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.
Alzheimer's - Dementia, Author Interviews, JAMA, Mental Health Research / 30.11.2017

MedicalResearch.com Interview with: [caption id="attachment_38640" align="alignleft" width="128"]Willemijn Jansen, PhD  Postdoctoral researcher Department of Psychiatry & Neuropsychology Maastricht University Medical Center School for Mental Health and Neuroscience Alzheimer Center Limburg  Dr. Jansen[/caption] 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.
Alzheimer's - Dementia, Author Interviews, NYU, Obstructive Sleep Apnea / 15.11.2017

MedicalResearch.com Interview with: [caption id="attachment_38308" align="alignleft" width="150"]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[/caption] 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
Alzheimer's - Dementia, Author Interviews, Medical Imaging, MRI / 06.10.2017

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.
Alzheimer's - Dementia, Author Interviews, Gender Differences, Genetic Research, JAMA / 29.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36657" align="alignleft" width="138"]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[/caption] 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.
Accidents & Violence, Alzheimer's - Dementia, Author Interviews, Depression, Geriatrics, Karolinski Institute / 11.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36437" align="alignleft" width="200"]Heidi Taipale, PhD Pharm Senior Researcher School of Pharmacy, University of Eastern Finland; and Department of Clinical Neuroscience Karolinska Institutet  Dr. Taipale[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Race/Ethnic Diversity / 26.07.2017

MedicalResearch.com Interview with: [caption id="attachment_36164" align="alignleft" width="125"]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[/caption] 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.
Author Interviews, Cognitive Issues, General Medicine, JAMA / 26.07.2017

MedicalResearch.com Interview with: [caption id="attachment_36157" align="alignleft" width="144"]Jochen René Thyrian, PhD German Center for Neurodegenerative Diseases (DZNE) Greifswald, Germany      Dr. Thyrian[/caption] 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
Alzheimer's - Dementia, Author Interviews, Obstructive Sleep Apnea / 26.07.2017

MedicalResearch.com Interview with: [caption id="attachment_36148" align="alignleft" width="168"]O. Michael Bubu, M.D., M.P.H., C.P.H Wheaton College Dr. Bubu[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Columbia, Nutrition / 24.07.2017

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
Aging, Author Interviews, Cognitive Issues, Lifestyle & Health / 20.07.2017

MedicalResearch.com Interview with: [caption id="attachment_36033" align="alignleft" width="133"]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[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Radiology / 18.07.2017

MedicalResearch.com Interview with: [caption id="attachment_35997" align="alignleft" width="161"]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[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Genetic Research, Mental Health Research / 23.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34811" align="alignleft" width="160"]Auriel Willette, M.S., Ph.D. Assistant Professor Departments of Food Science and Human Nutrition and Psychology Iowa State University Dr. Willette[/caption] 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.
Alzheimer's - Dementia, Author Interviews / 11.04.2017

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? [caption id="attachment_33830" align="alignleft" width="350"]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[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Lancet, Vaccine Studies / 01.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32529" align="alignleft" width="200"]Petr Novak, MD, PhD AXON Neuroscience Bratislava, Slovakia Dr. Petr Novak[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Genetic Research, PNAS / 12.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28670" align="alignleft" width="149"]Dr. Magdalena Sastre PhD Faculty of Medicine, Department of Medicine Senior Lecturer Imperial College London Dr. Magdalena Sastre[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Biomarkers / 01.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27583" align="alignleft" width="125"]Inflammatory Biomarkers May Presage Development of Alzheimer's Prof. Paul Morgan[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Brigham & Women's - Harvard, Education / 30.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27491" align="alignleft" width="180"]Deborah Blacker MD, ScD Director of the Gerontology Research Unit Department of Psychiatry Massachusetts General Hospital Dr. Deborah Blacker[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Nutrition / 28.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27409" align="alignleft" width="150"]William B. Grant, Ph.D. Director, Sunlight, Nutrition, and Health Research Center San Francisco, CA www.sunarc.org, Dr. William Grant[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Neurological Disorders / 05.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26735" align="alignleft" width="160"]Auriel Willette, PhD Assistant Professor Departments of Food Science and Human Nutrition, and Psychology Iowa State Universit Dr. Auriel Willette[/caption] 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.
Author Interviews, Biomarkers, CT Scanning, McGill, MRI, Nature / 13.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26102" align="alignleft" width="200"]Dr. Yasser Iturria Medina PhD Post-doctoral fellow Montreal Neurological Institute Dr. Y. M. Medina[/caption] 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.
Alzheimer's - Dementia, Author Interviews, Chemotherapy, Parkinson's / 13.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26087" align="alignleft" width="133"]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[/caption] 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).
Alzheimer's - Dementia, Author Interviews, Cost of Health Care, Geriatrics / 22.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25446" align="alignleft" width="142"]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[/caption] 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.
Alzheimer's - Dementia, Author Interviews / 01.06.2016

MedicalResearch.com Interview with: [caption id="attachment_24807" align="alignleft" width="126"]Prof. Margitta Elvers, PhD Institute of Hemostasis, Hemotherapy and Transfusion Medicine University Clinic of the Heinrich-Heine-University Düsseldorf Düsseldorf Germany Prof. Margitta Elvers[/caption] 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.
ALS, Alzheimer's - Dementia, Author Interviews, Nature / 07.05.2016

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.
Alzheimer's - Dementia, Author Interviews, Biomarkers / 27.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23823" align="alignleft" width="149"]Dr Anne Poljak Leader of the Proteomics Group Centre for Healthy Brain Ageing (CHeBA) UNSW, Australia Dr. Anne Poljak[/caption] 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).
Alzheimer's - Dementia, Author Interviews, JAMA, UCSF / 20.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23580" align="alignleft" width="149"]Jennifer S. Yokoyama, PhD Assistant Professor, Memory and Aging Center University of California, San Francisco Dr. Yokoyama[/caption] 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.  
Alzheimer's - Dementia, Author Interviews / 12.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23360" align="alignleft" width="142"]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[/caption] 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.