Aging, Alzheimer's - Dementia, Author Interviews / 27.07.2018

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. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 27.07.2018

MedicalResearch.com Interview with: 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.  (more…)
Alzheimer's - Dementia, Author Interviews, Heart Disease, JAMA, Metabolic Syndrome / 26.07.2018

MedicalResearch.com Interview with: Maude Wagner, PhD Student Biostatistics Team Lifelong Exposures, Health and Aging Team Bordeaux Population Health Research Center Inserm Univ. Bordeaux MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Many studies haves shown associations between cardiometabolic health and dementia in midlife, but associations later in life remain inconclusive. This study aimed to model concurrently and to compare the trajectories of major cardiometabolic risk factors in the 14 years before diagnosis among cases of dementia and controls. This study showed that demented persons presented a BMI decline and lower blood pressure (specifically systolic blood pressure) several years before dementia diagnosis that might be a consequence of underlying disease. In contrast, cases presented consistently higher blood glucose levels up to 14 years before dementia suggesting that high glycemia is a strong risk factor for dementia. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 25.07.2018

MedicalResearch.com Interview with: 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.  (more…)
Alzheimer's - Dementia, Author Interviews, Herpes Viruses / 20.07.2018

MedicalResearch.com Interview with: 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. (more…)
Alzheimer's - Dementia, Author Interviews, Obstructive Sleep Apnea, Sleep Disorders / 07.07.2018

MedicalResearch.com Interview with: “Woman sleeping” by Timothy Krause is licensed under CC BY 2.0Nathan E. Cross PhD, first author School of Psychology. Sharon L. Naismith, PhD, senior author Leonard P Ullman Chair in Psychology Brain and Mind Centre Neurosleep, NHMRC Centre of Research Excellence The University of Sydney, Australia  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Between 30 to 50% of the risk for dementia is due to modifiable risk factors such depression, hypertension, physical inactivity, obesity, diabetes and smoking. In recent years, multiple longitudinal cohort studies have observed a link between sleep apnoea and a greater risk (1.85 to 2.6 times more likely) of developing cognitive decline and dementia.  Furthermore, one study in over 8000 people also indicated that the presence of obstructive sleep apnoea (OSA) in older adults was associated with an earlier age of cognitive decline, and that treatment of OSA may delay the onset of cognitive impairment. This study reveals important insights into how sleep disorders such as OSA may impact the brain in older adults, as it is associated with widespread structural alterations in diverse brain regions. We found that reduced blood oxygen levels during sleep are related to reduced thickness of the brain's cortex in both the left and right temporal areas - regions that are important in memory and are early sites of injury in Alzheimer's disease. Indeed, reduced thickness in these regions was associated with poorer ability to learn new information, thereby being the first to link this structural change to memory decline. (more…)
Aging, Alzheimer's - Dementia, Author Interviews, JAMA, Ophthalmology / 29.06.2018

MedicalResearch.com Interview with: “Old Eyeglasses” by Leyram Odacrem is licensed under CC BY 2.0Diane Zheng MS NEI F-31 Research Fellow and a Ph.D. candidate in Epidemiology Department of Public Health Sciences University of Miami MedicalResearch.com: What is the background for this study? Response: Worsening vision and declining cognitive function are common conditions among older people. Understanding the association between them could be beneficial to alleviate age related cognitive decline. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Neurology / 25.06.2018

MedicalResearch.com Interview with: Paul Foster BMedSci(Hons) BMBS PhD FRCS(Ed) FRCOphth FRCS(Eng) Professor of Glaucoma Studies & Ophthalmic Epidemiology Research Theme Lead Integrative Epidemiology & Visual Function UCL Institute of Ophthalmology & Moorfields Eye Hospital London  MedicalResearch.com: What is the background for this study?  Response:  Dementia is the medical challenge of the moment – increasingly common, adversely impacting quality of life for millions, and a great worry for all. Efforts to identify treatments or interventions rely on being able to identify those people at greatest risk. Our motivation was to help identify those people, primarily to aid in the development of treatments through clinical trials. (more…)
Alzheimer's - Dementia, Author Interviews, Blood Pressure - Hypertension / 15.06.2018

MedicalResearch.com Interview with: Professor Archana Singh-Manoux, PhD, HDR Epidemiology Research Director (DR1), INSERM Honorary Professor, University College London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although there have been previous studies that have linked raised blood pressure in midlife to an increased risk of dementia in later life, the term ‘midlife’ has been poorly defined and ranged from 35 to 68 years. New findings from the long-running Whitehall II study of over 10,000 civil servants has found 50-year-olds who had blood pressure that was higher than normal but still below the threshold commonly used when deciding to treat the condition, were at increased risk of developing dementia in later life.  (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Medical Imaging, Memory / 12.06.2018

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. (more…)
Alzheimer's - Dementia, Author Interviews, Personalized Medicine, University of Pennsylvania / 15.05.2018

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 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. (more…)
Alzheimer's - Dementia, Author Interviews, Brain Injury, JAMA / 08.05.2018

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. 
(more…)
Alzheimer's - Dementia, Author Interviews, Merck, NEJM / 02.05.2018

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.  (more…)
Alzheimer's - Dementia, Author Interviews, NIH, PNAS, Sleep Disorders / 19.04.2018

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 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.  (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Epilepsy / 12.04.2018

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.  (more…)
ALS, Alzheimer's - Dementia, Author Interviews, JAMA / 09.04.2018

MedicalResearch.com Interview with: 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. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Parkinson's / 27.03.2018

MedicalResearch.com Interview with: 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. (more…)
Alzheimer's - Dementia, Author Interviews, Mental Health Research, Neurology / 16.02.2018

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. (more…)
Alzheimer's - Dementia, Author Interviews, Circadian Rhythm, JAMA / 30.01.2018

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.  (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers, JAMA, MRI / 12.01.2018

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 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. (more…)
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. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Geriatrics, Hearing Loss, JAMA / 11.12.2017

MedicalResearch.com Interview with: “Hear” by Jaya Ramchandani is licensed under CC BY 2.0David G. Loughrey, BA(Hons) NEIL (Neuro Enhancement for Independent Lives) Programme Trinity College Institute of Neuroscience, School of Medicine Trinity College Dublin, Dublin, Ireland MedicalResearch.com: What is the background for this study? Response: Age-related hearing loss, a common chronic condition among older adults, has emerged in the literature as a potential modifiable risk factor for dementia. This is of interest as current pharmacological therapies for dementias such as Alzheimer’s disease only offer symptom-modifying effects. Treatment of risk factors such as hearing loss may help delay the onset of dementia and may provide an alternate therapeutic strategy. However, there is variance in the research on hearing loss and cognition with some studies reporting a small or non-significant association. In this meta-analysis, we investigated this association and we only included observational studies that used standard assessments of cognitive function and pure-tone audiometry (the clinical standard). (more…)
Alzheimer's - Dementia, Author Interviews, BMJ, Education, Karolinski Institute / 10.12.2017

MedicalResearch.com Interview with:

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.

(more…)
Alzheimer's - Dementia, Author Interviews, Mineral Metabolism / 07.12.2017

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. (more…)
Alzheimer's - Dementia, Author Interviews / 06.12.2017

MedicalResearch.com Interview with: Professor Claude Wischik Co-Founder and Executive Chairman TauRx Pharmaceuticals MedicalResearch.com: What is the background for this study? What are the main findings? Response: The study TRx-237-005 was the second of two Phase 3 trials conducted by TauRx, and was specifically set up to investigate the efficacy and safety of LMTX® in 800 patients with mild Alzheimer’s disease at a dose of 100 mg twice daily compared to 4 mg twice daily (intended as an inactive control dose) over an 18-month treatment period. Results from this study were found to be consistent with those from the first Phase 3 study in mild to moderate Alzheimer’s disease, published in The Lancet [(TRx-237-015) Gauthier et al. 2016], indicating that patients obtained no benefit from LMTX® when it was taken in combination with existing approved drugs for Alzheimer’s disease and supporting the hypothesis that LMTX® might be effective as monotherapy at doses as low as 4 mg twice daily. Please refer to the press release for full study results.   (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Mental Health Research / 30.11.2017

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  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. (more…)
Alzheimer's - Dementia, Author Interviews, NYU, Obstructive Sleep Apnea / 15.11.2017

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  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 (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Genetic Research, Nature / 07.11.2017

MedicalResearch.com Interview with: Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer's disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer's patients than in human controls of the same age; and it is lower in the elderly with respect to young adults. Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho. (more…)
Alzheimer's - Dementia, Author Interviews, Johns Hopkins, Memory, Mental Health Research / 04.11.2017

MedicalResearch.com Interview with: Keenan A. Walker, PhD Johns Hopkins University School of Medicine Baltimore, MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is quite a bit of evidence linking immune function with dementia. For example, several of the risk genes for Alzheimer’s disease are known to play a key role in immune functioning and the regulation of inflammation. We conducted the current study to determine whether systemic inflammation earlier in life might be a risk factor for neurodegeneration decades later. This long temporal window allows us to get closer to understanding causality. That is, which comes first – systemic inflammation or brain volume loss. Using a large community sample, we found that individuals with higher levels of blood inflammatory markers during midlife tended to have smaller brain volumes in select regions and reduced memory ability as older adults. We found the strongest associations between systemic inflammation and brain volume loss in brain regions most vulnerable Alzheimer’s disease. (more…)