Benzodiazepines Linked to Modest Increased Risk of Alzheimer’s

MedicalResearch.com Interview with:
MedicalResearch.comVesa Tapiainen, MD
School of Pharmacy, University of Eastern Finland
Research Centre for Comparative Effectiveness and Patient Safety
University of Eastern Finland Kuopio, Finland

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

Response: Alzheimer’s disease is a non-curable dementing disease and a major health concern and thus, identification of potential modifiable risk factors, such as benzodiazepines, is important. Benzodiazepines and related drugs are commonly used among older people as every fourth older people use them.

Benzodiazepines and related drugs were associated with modestly increased risk of Alzheimer’s disease. A dose-response relationship was observed with higher cumulative dose and longer use periods being associated with higher risk of Alzheimer’s disease. The risk associated with larger cumulative doses was partly explained by more common use of other psychotropics among these persons.  Continue reading

Altered Bile Acid Metabolites in Mild Cognitive Impairment and Alzheimer’s Disease

MedicalResearch.com Interview with:

Kwangsik Nho, PhD Assistant Professor of Radiology & Imaging Sciences Indiana University School of Medicine Indianapolis, IN, 

Dr. Kwangsik Nho

Kwangsik Nho, PhD
Assistant Professor of Radiology & Imaging Sciences
Indiana University School of Medicine
Indianapolis, IN

MedicalResearch.com: What is the ADNI (Alzheimer’s Disease Neuroimaging Initiative)?

Response: The initial phase (ADNI-1) was launched in 2003 to test whether serial magnetic resonance imaging (MRI), position emission tomography (PET), other biological markers, and clinical and neuropsychological assessment could be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer’s Disease (AD). ADNI-1 was extended to subsequent phases (ADNI-GO, ADNI-2, and ADNI-3) for follow-up for existing participants and additional new enrollments. To our knowledge, the ADNI cohort (370 cognitively normal older adults, 98 patients with significant memory concern, 284 early MCI, 505 late MCI, and 305 patients with AD) uniquely has multi-omics data sets including metabolomics and structural and functional neuroimaging data (MRI, PET) as well as rich clinical and fluid biomarker data on the same participants.

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Forgetting To Do Things? Try Acting in Advance

MedicalResearch.com Interview with:

Dr Antonina Pereira - CPsychol, PhD, FHEA, AFBPsS Head of Department of Psychology & Counselling University of Chichester Chichester, West Sussex UK

Dr. Pereira

Dr Antonina Pereira – CPsychol, PhD, FHEA, AFBPsS
Head of Department of Psychology & Counselling
University of Chichester
Chichester, West Sussex UK

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

Response: Prospective memory (PM) is the ability to remember to perform future activities, such as remembering to take medication or remembering to attend an appointment. Prospective memory tasks pervade our daily lives, and PM failures, although sometimes merely annoying (e.g., forgetting an umbrella at home on a rainy day), can have serious and even life-threatening consequences (e.g., forgetting to turn off the stove).

The fulfilment of such delayed intended actions can indeed be an early indicator of Alzheimer’s disease, with prospective memory failures representing one of the most prominent memory concerns in older adulthood and a fundamental requirement for independent living across the lifespan.

We aimed to address this issue by exploring the potential benefits of a purposefully designed technique, encoded enactment, where participants were encouraged to act through the activity they must remember to do.

This particular study was the fruit of an international research collaboration led by the University of Chichester and including members from Radboud University Nijmegen, Sussex Partnership NHS Foundation Trust and the Faculty of Medicine of the University of Lisbon.

Our team has explored the potential benefits of this specific encoding strategy for healthy younger adults, healthy older adults as well as for patients with mild cognitive impairment.

Results were very encouraging: All age groups reported improvement in prospective memory, but this was particularly evident in older patients with mild cognitive impairment, that is, potentially in the early stages of Alzheimer’s disease.

The study suggests that encouraging people in this category to adopt enactment as a means to enhance prospective memory could result in them leading independent, autonomous lives for longer.

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Alzheimer’s Disease: Genes Modify Effect of High Fat Diet

MedicalResearch.com Interview with:
The Jackson LaboratoryCatherine Kaczorowski, Ph.D.

Associate Professor and Evnin Family Chair in Alzheimer’s Research
Kristen O’Connell, Ph.D., Assistant Professor
Amy Dunn, Ph.D., Postdoctoral Associate
The Jackson Laboratory


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

Dr. Amy Dunn: “Alzheimer’s disease is complex, with both genetic and environmental factors determining symptom onset and disease progression, though our current understanding of how genetic and environmental factors interact to influence disease risk is incomplete. We recently developed a panel of genetically diverse mice carrying human familial AD mutations (AD-BXDs) that better model human AD in order to determine how genetics and diet interact to modify disease onset and severity.

We fed a high fat diet to AD-BXDs and monitored metabolic and cognitive function over the duration of the HFD feeding.  We observed accelerated working memory decline in most of the AD-BXD mouse strains, however, the impact of high fat diet on memory was dependent on individual genetic differences across the panel, with some AD-BXD strains maintaining cognitive function on high fat diet (resilient strains).

Our data suggest that diet and genetic background interact to mediate vulnerability to AD pathogenesis, and that metabolic factors (e.g. obesity, body composition) that may contribute to cognitive decline differentially in normal aging versus AD. “

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Plasma Component Investigated To Reverse Age-Related Cognitive Disorders

MedicalResearch.com Interview with:
alkahestIan Gallager, MS
Scientist at Alkahest Inc.
San Francisco Bay Area 

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

Response: Our research is aimed to develop novel therapeutics for age-related disorders from fundamental understandings of blood plasma. This expands upon work initially performed in the Wyss-Coray lab at Stanford utilizing a model of parabiosis. By surgically conjoining the blood supplies between a young and aged mouse, they established that beneficial effects were observed in the aged mouse brain, suggesting that there are proteins in young blood which have enhancing properties.

The research presented at AAIC was the culmination of several years of model and dosing paradigm development utilizing both human plasma and a proprietary fractionated plasma product leading to advances for clinical application.

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Novel Models of Late-Onset Alzheimer’s Disease Based on GWAS

MedicalResearch.com Interview with:

Gregory Carter

Dr. Carter

Gregory Carter, PhD
Associate Professor at The Jackson Laboratory

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

Response: Animal models for late-onset Alzheimer’s disease (LOAD) will be of significant benefit for the discovery and characterization of links between specific genetic factors and the molecular pathways associated with the disease. To date, most animal models have been based on rare, early-onset Alzheimer’s disease genes that incompletely capture the complexity of LOAD and have not translated well to therapies. Therefore, developing and utilizing animal models based on genes hypothesized to play a role in LOAD will provide new insights into its basic biological mechanisms.  Continue reading

Whole-Exome Analysis of Late-Onset Alzheimer’s Disease Reveals Novel Candidate Genes Involved in Cognitive Function

MedicalResearch.com Interview with:

Dr. Carter

Gregory Carter, PhD
Associate Professor at The Jackson Laboratory

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

Response: Late-onset Alzheimer’s disease (LOAD) is the most common form of the disease and the major cause of dementia in the aging population. To date, the complex genetic architecture of LOAD has hampered both our ability to predict disease outcome and to establish research models that effectively replicate human disease pathology.

Therefore, most basic research into Alzheimer’s disease has focused on early-onset forms caused by mutations in specific genes, which has provided key biological insights but to date has not translated to effective disease preventatives or cures.

Our study analyzes both common and rare human genetic variants to identify those significantly associated with .late-onset Alzheimer’s disease, beginning with a large data set from the Alzheimer’s Disease Sequencing Project. We also analyzed RNA sequencing data from post-mortem human and mouse model samples to prioritize candidate genes.

We found a new common coding variant significantly associated with disease, in addition to those in genes previously associated with late-onset Alzheimer’s disease. We also found five candidate genes conferring a significant rare variant burden.  Continue reading

Could Treatment for Herpes Virus Reduce Risk of Alzheimer’s Disease?

MedicalResearch.com Interview with:

This photograph depicts a close-up of the lips of a patient with a herpes simplex lesion on the lower lip, due to the herpes simples virus-1 (HSV-1) CDC image

This photograph depicts a close-up of the lips of a patient with a herpes simplex lesion on the lower lip, due to the herpes simples virus-1 (HSV-1)
CDC image

Prof Ruth Itzhaki
Emeritus Professor
Division of Neuroscience & Experimental Psychology
The University of Manchester

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

Response: The background arises from the unexpected discovery, made by my lab almost 30 years ago, that the DNA of the common virus, herpes simplex virus type 1 (HSV1), known as the “cold sore” virus, was present in a high proportion of autopsy brains from elderly humans. Subsequently, we found that HSV1, when in brain of people who have a specific genetic factor, APOE-e4, confers a strong risk of developing Alzheimer’s disease. We found also a parallelism with cold sores in that APOE-e4 is a risk for the sores, which occur in about 25-40% of people infected with HSV1.

We then looked for links between the effects of HSV1 infection of cells in culture and AD, and found some major associations between virus and disease.

Firstly, HSV1 causes an increase in the formation of a small protein called beta amyloid, which is the main component of the abnormal “plaques” seen in Alzheimer’s Disease brains.

Secondly, we discovered that in AD brains, the viral DNA is located precisely within amyloid plaques, which suggests that the virus is responsible for the formation of these abnormal structures. Thirdly, we confirmed the finding of another lab that HSV1 causes the increased formation of an abnormal form of the protein known as tau, which is the main component of the other characteristic abnormality of Alzheimer’s Disease brains – “neurofibrillary tangles”.

All these discoveries suggested that the damage caused by HSV1 leads eventually to the development of AD.

Lastly, we showed that treating HSV1-infected cells in culture greatly reduces the formation of beta amyloid and abnormal tau. This suggests that antiviral agents might be used for treating Alzheimer’s Disease patients.

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Amyloid PET Scan Useful in Memory Evaluation

MedicalResearch.com Interview with:
Arno de Wilde, MD / PhD candidate

Department of Neurology & Alzheimer Center
Amsterdam Neuroscience
VU University Medical Center
Amsterdam, the Netherlands

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

Response: Previous studies assessing the clinical utility of amyloid imaging used very selected research populations, limiting the translatability to clinical practice. In contrast, we used an unselected memory clinic cohort, offering amyloid PET to ALL patients visiting our memory clinic, and for the purpose of this study, we implemented amyloid PET in our routine diagnostic work-up. Our results demonstrate that amyloid PET has important consequences, in terms of diagnosis and treatment changes, for a significant number of patients within a situation that closely resembles clinical practice. I think that these results are an important step in ‘bridging the gap’ between using amyloid PET in a research setting versus daily clinical practice.

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Alzheimer Study: New Drug Did Not Reduce Cognitive Decline

MedicalResearch.com Interview with:
Dr. Michael F. Egan MD

Merck & Co.
North Wales, PA 19454  

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

Response: A leading theory of Alzheimer’s Disease is that it is caused by the buildup of amyloid plaques in the brain. Amyloid is composed of a sticky peptide called Abeta.  Abeta production can be blocked by Inhibiting an enzyme called BACE.  In animal models, BACE inhibtion prevent amyloid accumulation.  We aimed to see if a potent BACE inhibitor would slow clinical decline in Alzheimer’s Disease.

EPOCH was a Phase 2/3 randomized, placebo-controlled, parallel-group, double-blind study evaluating efficacy and safety of two oral doses of verubecestat an investigational BACE inhibitor, administered once-daily versus placebo in patients with mild-to-moderate AD currently using standard of care treatment. The primary efficacy outcomes of the study are the change from baseline in cognition (assessed using the Alzheimer’s Disease Assessment Scale Cognitive Subscale, or ADAS-Cog),  as well as the change from baseline in function (assessed using the Alzheimer’s Disease Cooperative Study – Activities of Daily Living, or ADCS-ADL)  after 78 weeks of treatment.

Following the recommendation of the external Data Monitoring Committee (eDMC), which assessed overall benefit/risk during  the trial,  the study was stopped early, as there was “virtually no chance of finding a positive clinical effect.”

Verubecestat did not reduce cognitive or functional decline in patients with mild-to moderate Alzheimer’s disease and was associated with treatment-related adverse events.  Continue reading

Lack of Awareness of Cognitive Issues Presages Alzheimer’s Disease

MedicalResearch.com Interview with:
Joseph Therriault

Integrative Program in Neuroscience 

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

Response: Neurologists have known for a long time that Anosognosia, or unawareness of illness, appears in individuals with Alzheimer’s disease. For example, these patients will have diminished awareness of their memory loss, and will also engage in dangerous behaviors, such as leaving the house to go for a walk, without knowing they are at high risk of getting lost.

However, it was not known if decreased awareness of cognitive problems existed in the pre-dementia phase of Alzheimer’s disease. In our study, we compared the ratings of cognitive decline from the patient and their close relative, who also filled out the same questionnaire. When a patient reported having no cognitive problems but the family member reported significant difficulties, the patient was considered to have poor awareness of illness.

We found that patients who are less aware had increased disease pathology, and were nearly three times as likely to progress to dementia within two years, even when taking into account other factors like genetic risk, age, gender and education. The increased progression to dementia was mirrored by increased brain metabolic dysfunction in regions vulnerable to Alzheimer’s disease.

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Fragmented Circadian Rhythm Associated with Preclinical Alzheimer’s Disease

MedicalResearch.com Interview with:
“mirror clock” by tourist_on_earth is licensed under CC BY 2.0Yo-El Ju, MD

Assistant Professor of Neurology
Sleep Medicine Section
Washington University School of Medicine

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

Response: The background for this study is that prior studies have shown that people with Alzheimer’s Disease have poor circadian clock function, for example sleeping during the day and being awake or agitated at night. Autopsy studies have shown that people with Alzheimer’s Disease have degeneration in the “clock” part of their brains. In this study, we wanted to examine whether there were any circadian problems much earlier in Alzheimer’s Disease, when people do not have any memory or thinking problems at all.

We measured circadian function in 189 people with an actigraph, which is an activity monitor worn like a watch, for 1-2 weeks. Brain scans and studies of cerebrospinal fluid were used to determine who had preclinical Alzheimer’s Disease, meaning they have the brain changes of Alzheimer’s but do not have symptoms yet.  Continue reading

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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