Amyloid PET Scan Can Predict Progression to Alzheimer’s in Patients With Mild Cognitive Impairment

MedicalResearch.com Interview with:

David A. Wolk, MD Associate Professor Department of Neurology Co-Director, Penn Memory Center Associate Director, Alzheimer’s Disease Core Center University of Pennsylvania

Dr. Wolk

David A. Wolk, MD
Associate Professor
Department of Neurology
Co-Director, Penn Memory Center
Associate Director, Alzheimer’s Disease Core Center
University of Pennsylvania

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

Response: Mild Cognitive Impairment (MCI) is a state when individuals have mild memory problems, but not enough to impact day-to-day function.  Many patients with MCI are on the trajectory to developing Alzheimer’s Disease dementia, but about half will not and remain stable.  As such, patients with MCI are often uncertain about the likelihood they should expect to decline in the future which obviously may be associated with considerable anxiety and this may delay opportunities for them to plan for the future or begin therapeutic interventions.

This study examined the degree to which amyloid PET, which detects the amyloid pathology of Alzheimer’s Disease, a measure of shrinkage of the hippocampus with MRI, and cognitive measures predicted development of dementia over 3 years.  We found that each of these measures enhances prediction of whether an individual will or will not develop dementia in the future.  If all of these measures are positive, one has a very high risk of progression whereas if amyloid PET and the MRI measurement are normal, there is very little risk of progression. Continue reading

Vets with Head Injury More Likely To Develop Dementia

MedicalResearch.com Interview with:
Deborah E. Barnes, PhD, MPH Professor, UCSF Weill Institute for Neurosciences Departments of Psychiatry and Epidemiology & Biostatistics University of California, San Francisco: http://profiles.ucsf.edu/deborah.barnes Research Health Sciences Specialist, San Francisco VA Medical Center Senior Investigator, Tideswell at UCSF: http://www.tideswellucsf.org/ Deborah E. Barnes, PhD, MPH

Professor, UCSF Weill Institute for Neurosciences
Departments of Psychiatry and Epidemiology & Biostatistics
University of California, San Francisco: http://profiles.ucsf.edu/deborah.barnes
Research Health Sciences Specialist
San Francisco VA Medical Center

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

  • Previous studies have found a link between moderate to severe head injuries and increased dementia risk.
  • The association between mild head injuries and dementia – especially mild head injury that doesn’t result in loss of consciousness – is less well established
  • We examined the association between mild head injuries with and without loss of consciousness and dementia diagnoses in nearly 360,000 Veterans receiving care in the VA health care system.
  • We found that Veterans with a head injury diagnoses were two to four times more likely to be diagnosed with dementia than those without head injury diagnoses.
  • The risk of dementia diagnosis was doubled in Veterans who experienced head injury without loss of consciousness compared to those with no head injury. 

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Some Depression and Overactive Bladder Drugs Linked to Dementia

Medicalresearch.com Interview with:

Professor Phyo Kyaw Myint Chair in Old Age Medicine University of Aberdeen

Prof. Myint

Professor Phyo Kyaw Myint
Chair in Old Age Medicine
University of Aberdeen

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

Response: We have previously studied the potential harmful effects of a group of medications called anticholinergics. They can have side effects on central as well peripheral systems. The link between use of these drugs and dementia is less well understood due to limitations of previous studies.

We used large GP practices data from the UK with long term follow up and examined this association using robust statistical methods.

Medicalresearch.com: What are the main findings?

Response: Key findings are:

  • Drugs with anticholinergic properties which are used to treat depression, urological conditions (e.g. for overactive bladder) and Parkinsonism are linked to development of dementia.
  • Drugs with similar properties which are used to treat gut disorders and heart conditions are not found to be linked to dementia
  • Drugs with low level of anticholinergic effect are not linked to dementia

Medicalresearch.com: What should readers take away from your report?

Response: Clinicians should use the drugs with high level of anticholinergic burden cautiously. Also attempts should be made whenever appropriate to reduce or replace with similar drugs but without such properties.

Medicalresearch.com: What recommendations do you have for future research as a result of this study?

Response: We need to ensure confounding effects are minimised by conducting carefully designed prospective studies. Further clinical trial evidence of benefit of deprescribing of these medications (when possible) in at risk populations is also urgently warranted.

Medicalresearch.com: Is there anything else you would like to add? Any disclosures?

Response: In the absence of trial evidence, this study provides best available evidence using robust statistical methods in the largest study of its kind and will help clinicians in making treatment choices for the benefit of the patients.

Citation:

Anticholinergic drugs and risk of dementia: case-control study

BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k1315 (Published 25 April 2018)Cite this as: BMJ 2018;361:k1315

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

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

Sleep Deprivation Leads to Build Up of Junk Amyloid in Brain

MedicalResearch.com Interview with:

Nora D. Volkow MD Senior Investigator Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health, Bethesda, MD 20892

Dr. Nora Volkow

Nora D. Volkow MD
Senior Investigator
Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health, Bethesda, MD 20892

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

Response: Findings from animal studies had shown that sleep deprivation increased the content of beta-amyloid in brain, which is a risk factor for Alzheimer’s disease.  We wanted to test whether this also happened in the human brain after one night of sleep deprivation. We found that indeed one night of sleep deprivation led to an accumulation of beta amyloid in the human brain, which suggest that one of the reasons why we sleep is to help clean our brain of degradation products that if not removed are toxic to brain cells.  Continue reading

Link Between Epilepsy Drugs and Increased Risk of Dementia

MedicalResearch.com Interview with:
Britta Haenisch, PhD

Pharmacoepidemiology in Neurodegenerative Disorders
German Center for Neurodegenerative Diseases,
DZNE 

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

Response: Antiepileptic drugs (AEDs) have been shown to affect cognition by suppressing neuronal excitability and increasing inhibitory neurotransmission. Previous studies suggested that AEDs may be associated with cognitive adverse effects. Therefore, we evaluated the association between AED use and incident dementia and Alzheimer’s disease (AD).

We utilized large longitudinal datasets from Finnish health registers and from German health insurance data. The case-control analyses was adjusted for several potential confounders like comorbidities and polypharmacy. The inclusion of a lag time between . Antiepileptic drugs use and dementia diagnosis allowed minimization of protopathic bias.

Our study provides an association between regular prescription of  antiepileptic drugs with known cognitive adverse effects and the occurrence of dementia and AD in patients aged 65 years and older.  Continue reading

Genetic Overlap Between Some Types of ALS and and Dementia

MedicalResearch.com Interview with:

Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis

Dr. Karch

Celeste Karch, PhD
Assistant Professor of Psychiatry
Molecular mechanisms underlying tauopathies
Washington University School of Medicine
St Louis

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

Response: Nearly half of all patients with amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disorder, develop cognitive problems that affect memory and thinking. Why a disease that primarily affects movement also disrupts thinking has been unclear.

Our findings suggest that genetic connections between the two disorders may explain why they share some of the same features and suggest that some drugs developed to treat ALS also may work against frontotemporal dementia and vice versa. We used a statistical method in almost 125,000 individuals with ALS, frontotemporal dementia (FTD), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease and Parkinson’s disease to determine whether there are common genetic variants that increase risk for multiple neurodegenerative diseases.

We found that common variants near the MAPT gene, which makes the tau protein, increases risk for ALS. MAPT has previously had been associated with diseases including frontotemporal dementia and Alzheimer’s disease. But the gene hadn’t been linked to ALS. We also identified variations in a second gene, BNIP1, which normally plays an important role in protecting against cell death, increased the risk of both ALS and frontotemporal dementia. ImportantlyBNIP1 mRNA levels were altered in people who had ALS and in patients with frontotemporal dementia, suggesting the BNIP1 may be a potential therapeutic target for both disorders.

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Simple Screening Tool Predicts Parkinson’s Patients At Risk of Dementia

MedicalResearch.com Interview with:

Benjamin Dawson, B.Sc.  MD Candidate 2020

Benjamin Dawson

Benjamin Dawson, B.Sc.
MD Candidate 2020

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

Response: Dementia in Parkinson’s Disease is one of its most feared complications, and may happen eventually to most patients if they reached advanced age. Identifying those at especially high risk of dementia has important potential implications – it would facilitate clinical counselling, it has treatment implications (e.g. knowing a person is likely to get dementia in the near future would probably steer you away from certain medications and towards others).  Most critically, it can help select patients for trials to prevent dementia.

While several factors that show high risk for dementia in Parkinson’s disease have previously been described, these have yet to shape patient-care, either because they are not very strong predictors, or they are not user-friendly.  So, we designed a very simple clinical screening tool, called the Montreal Parkinson’s Risk of Dementia Scale (MoPaRDS).  It took predictors of dementia that were established from large-scale studies and boiled them down into a simple 8-point scale that uses information that you can get in a simple office visit.  The 8 predictors were being over 70, being male, having a blood pressure drop with standing, showing early mild cognitive changes, having a symmetric bilateral disease (that is, one side not clearly worse than the other), experiencing falls or freezing, having experienced hallucinations, and having symptoms of REM sleep behavior disorder (‘acting out’ the dreams at night).

When we tested the scale in a combined cohort of 607 patients with Parkinson’s (of whom 70 developed dementia over mean follow-up of 4.4-years) a positive MoPaRDS screen (≥4 out of 8 items) identified 14-fold increased risk of dementia compared to a negative screen. We recommend dividing the scale into three categories; low-, intermediate- and high-risk. Those in the highest score group (MoPaRDS, 6-8) had a 14.9% risk of developing dementia each year, while those with the lowest scores (MoPaRDS, 0-3) had only 0.6% annual risk.  So, these simple measures can be pretty powerful predictors of dementia. 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