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…)
AACR, Alzheimer's - Dementia, Author Interviews, Cancer Research, Cognitive Issues, Colon Cancer, UCSF / 24.10.2017

MedicalResearch.com Interview with: Yingjia Chen, M.Sc, MPH, Ph.D. Postdoctoral Fellow University of California, San Francisco  MedicalResearch.com: What is the background for this study? Response: Both colon cancer and dementia are prevalent among the elderly and have a high risk of co-occurrence. Previous studies found that patients with dementia were treated less aggressively. In this study, we hypothesized that presence of pre-existing dementia was associated with worse survival for stage III colon cancer patients, and that post-operative chemotherapy was on the causal pathway. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers, JAMA, Personalized Medicine / 17.10.2017

MedicalResearch.com Interview with: Ingrid S. van Maurik, MSc Department of Neurology and Alzheimer Center Department of Epidemiology and Biostatistics Amsterdam Neuroscience VU University Medical Center Amsterdam, the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: CSF and MRI biomarkers are increasingly used in clinical practice, but their diagnostic and prognostic value is not perfect. Furthermore, criteria do not specify how to deal with conflicting or borderline results, or how to take patient characteristics into account. Therefore, optimal use of these biomarkers in clinical practice remains challenging. As part of the ABIDE project, we constructed biomarker-based prognostic models (CSF, MRI and combined) that enable prediction of future Alzheimer’s disease, or any type of dementia, in individual patients with mild cognitive impairment. When using these models, any value can be entered for the variables, resulting in personalized probabilities with confidence intervals. (more…)
Alzheimer's - Dementia, Author Interviews, Medical Imaging, MRI / 06.10.2017

MedicalResearch.com Interview with: Dr. Sanja Josef Golubic, dr. sc Department of Physics, Faculty of Science University of Zagreb, Croatia MedicalResearch.com: What is the background for this study? Response: Our study was aimed to search the topological biomarker of Alzheimer’s disease. A recent evidences suggest that the decades long progression of brain degeneration that is irreversible by the stage of symptomatic Alzheimer’s disease, may account for failures to develop successful disease-modifying therapies. Currently, there is a pressing worldwide search for a marker of very early, possibly reversible, pathological changes related to Alzheimer’s disease in still cognitively intact individuals, that could provide a critical opportunity for evolving of efficient therapeutic interventions. Three years ago we reported the discovery of the novel, fast brain pathway specialized for rapid processing of the simple tones. We named it gating loop. Gating loop directly links auditory brain areas to prefrontal brain area. We have also noticed the high sensitivity of the gating loop processing on AD pathology. It was inspiration to focus our Alzheimer’s disease biomarker search in the direction of prefrontal brain activation during listening of simple tones. (more…)
Alzheimer's - Dementia, Author Interviews, Infections, Neurology, Parkinson's / 22.09.2017

MedicalResearch.com Interview with: Rima McLeod, M.D., F.A.C.P, F.I.D.S.A Professor of Ophthalmology and Visual Sciences,Pediatrics (Infectious Diseases), and The College, Director, Toxoplasmosis Center, Senior Fellow,Institute of Genomics, Genetics and Systems Biology, Member, Commitees on Immunology, and Molecular Medicine and Pathogenesis, Member Global Health Center, Affiliate CHeSS; Attending Physician, Chicago Medicine, The University of Chicago MedicalResearch.com: What is the background for this study? * One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. * Approximately fifteen million of these have congenital toxoplasmosis. * The parasite interconverts between slow-growing, encysted bradyzoites and rapid-growing tachyzoites. * In mice, T. gondii creates a chronic intra-neuronal infection and an inflammatory process. * Mice with acute and chronic infection have alterations in neurotransmitters, memory, seizures, and neurobehavior. * Some epidemiologic-serologic studies show associations between seropositivity for T. gondii and human neurologic diseases, for example, Parkinson’s and Alzheimer’s diseases. * Although neurobehavioral disease is associated with seropositivity, causality is unproven. * Serologic studies of humans with diverse genetics are not optimal to detect strong associations or directionality. * Epidemiologic associations also do not reveal parasite-modulated gene networks in human brain that could provide insights into how to cure and prevent resultant diseases. * We need integrative approaches to examine relationships between brain parasitism and other brain diseases, to provide a foundation to identify key pathways and molecules for drug and vaccine design * To address these problems, we considered two central questions: (i) If chronic brain parasitism associates with other neurologic diseases, what are they? And (ii) Which macromolecular networks are modulated by the parasite in human brain that lead to neuropathology which could underpin and facilitate design of treatments? * We hypothesized that a systems approach integrating multiple levels of host parasite interactions might resolve these questions. * To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain.  (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, JAMA / 05.09.2017

MedicalResearch.com Interview with: Carol A. Derby, Ph.D. Research Professor, The Saul R. Korey Department of Neurology Research Professor, Department of Epidemiology & Population Health Louis and Gertrude Feil Faculty Scholar in Neurology Albert Einstein College of Medicine Bronx, NY 10461 MedicalResearch.com: What is the background for this study? Response: The population over the age of 85 is expected to triple in the coming decades, and with the aging of the population, the number of individuals living with dementia is projected to increase dramatically. While dementia prevalence rates are driven by demographic shift to older ages, changes in dementia incidence- the rate at which new cases are diagnosed, would also impact the proportion of the population affected in the coming decades. Recently, studies have suggested that dementia incidence rates may be declining in some populations, although the results have not been consistent. Better understanding trends in dementia rates is important for public health planning. Our objective was to determine whether there has been a change in the incidence of dementia diagnosis within a community residing group of over older adults followed by the Einstein Aging Study, at the Albert Einstein College of Medicine, in the Bronx, NY between the years 1993 and 2015. To accurately characterize trends over time in disease rates requires separating the effects of age and the effects of calendar time. Therefore, we conducted a birth cohort analysis in which we examined age specific dementia incidence rates by birth year, for individuals born between 1910 and 1940. The analysis included over 1300 individuals over the age of 70, who were free of dementia when they enrolled in the study. Dementia was diagnosed using identical criteria over the entire study period, and study recruitment was also consistent over the period. We also examined trends in cardiovascular co-morbidities that have been related to dementia risk, as well as trends in education.  (more…)
Alzheimer's - Dementia, Author Interviews, Gender Differences, Genetic Research, JAMA / 29.08.2017

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  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. (more…)
Accidents & Violence, Alzheimer's - Dementia, Author Interviews, Depression, Geriatrics, Karolinski Institute / 11.08.2017

MedicalResearch.com Interview with: 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. (more…)
Alzheimer's - Dementia, Author Interviews, Race/Ethnic Diversity / 26.07.2017

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 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. (more…)