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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