Highlights •We investigated whether recent and/or remote depression was associated with increased risk of Alzheimer’s Dementia (AD) and whether this risk differed between men and women. •Recent depression was independently associated with increased risk of incident AD while remote depression was not. Recent depression was predictive of AD development in females, but not in males, while sex did not moderate recent depression-associated risk of developing … Continue reading #Depression and increased risk of #Alzheimer’s #dementia: longitudinal analyses of modifiable risk and sex-related factors.
Background:Aging is considered the most important risk factor for Alzheimer’s disease (AD). Recent research supports the theory that immunotherapy targeting the “oligomeric” forms of amyloid-β (Aβ) may halt the progression of AD. However, previous clinical trial of the vaccine against Aβ, called AN1792, was suspended due to cases of meningoencephalitis in patients. Objective:To develop a peptide sensitized dendritic cells (DCs) vaccine that would target oligomer … Continue reading An Immunomodulatory Therapeutic #Vaccine Targeting Oligomeric #Amyloid-β
Experimental sleep-wake disruption in rodents and humans causally modulates β-amyloid (Aβ) dynamics (e.g., [1, 2, 3]). This leads to the hypothesis that, beyond cross-sectional associations, impaired sleep structure and physiology could represent prospective biomarkers of the speed with which Aβ accumulates over time. Here, we test the hypothesis that initial baseline measures of non-rapid eye movement (NREM) sleep slow-wave activity (SWA) and sleep quality (efficiency) … Continue reading #Sleep Disturbance Forecasts β- #Amyloid Accumulation across Subsequent Years
The oxidative degradation of lipids has been shown to be implicated in the progression of several neurodegenerative diseases and modulating lipid peroxidation may be efficacious for treating Alzheimer’s disease (AD). This hypothesis is strengthened by recent findings suggesting that oxytosis/ferroptosis, a cell death process characterized by increased lipid peroxidation, plays an important role in AD-related toxicities. CMS121 is a small molecule developed against these aspects … Continue reading CMS121, a fatty acid synthase inhibitor, protects against excess lipid peroxidation and inflammation and alleviates cognitive loss in a transgenic mouse model of #Alzheimer’s disease
The underlying mechanisms leading to dementia and Alzheimer’s disease (AD) are unclear. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be associated with cognitive decline, but population‐based evidence is lacking.. ..Change in cognitive performance was assessed in participants of the Aberdeen Birth Cohort of 1936 using longitudinal Raven’s progressive matrices (RPM) between 2000 and 2004. Multiple linear regression was used to estimate … Continue reading Circulating asymmetric #dimethylarginine and #cognitive decline: A 4‐year follow‐up study of the 1936 Aberdeen Birth Cohort
Potential drug treatments for Alzheimer’s disease (AD) may be found by identifying compounds that block the assembly of the microtubule-associated protein tau into neurofibrillar tangles associated with neuron destabilization and cell death. Here, a small library of structurally diverse compounds was screened in vitro for the ability to inhibit tau aggregation, using high-throughput synchrotron radiation circular dichroism as a novel tool to monitor the structural … Continue reading Circular Dichroism Spectroscopy Identifies the β-Adrenoceptor Agonist Salbutamol As a Direct Inhibitor of Tau Filament Formation in Vitro
Using data from the Chicago Health and Aging Project (CHAP; n = 1,845) and the Rush Memory and Aging Project (MAP; n = 920), we defined a healthy lifestyle score on the basis of nonsmoking, ≥150 min/wk moderate/vigorous-intensity physical activity, light to moderate alcohol consumption, high-quality Mediterranean-DASH Diet.. ..During a median follow-up of 5.8 years in CHAP and 6.0 years in MAP, 379 and 229 … Continue reading Healthy #lifestyle and the risk of #Alzheimer dementia
The Cognitive Debt hypothesis proposes that repetitive negative thinking (RNT), a modifiable process common to many psychological risk factors for Alzheimer’s disease (AD) may itself increase risk. We sought to empirically examine relationships between RNT and markers of AD, compared with anxiety and depression symptoms. ..RNT was associated with decline in global cognition (P = .02); immediate (P = .03) and delayed memory (P = … Continue reading Repetitive negative #thinking is associated with #amyloid, tau, and cognitive decline
Findings from existing prospective observational studies on the protective associations of flavonoid intake and the risk of Alzheimer disease and related dementias (ADRD) are inconsistent largely due to limitations of these studies.. ..Over an average follow-up of 19.7 y in 2801 participants (mean baseline age = 59.1 y; 52% females), there were 193 ADRD events of which 158 were AD. After multivariate and dietary adjustments, … Continue reading Long-term dietary #flavonoid intake and risk of #Alzheimer disease and related dementias in the Framingham Offspring Cohort
Neuroinflammation is part of the complex immune response within the central nervous system (CNS), whose details have been partially elucidated. The CNS immune response involves elements carried from the periphery and resident elements, mainly represented by glial cells. These cells drive neuroinflammation, which can be roughly defined as an articulated physiological response characterized by the production of a plethora of inflammatory mediators that alter the … Continue reading Neuroinflammation in Alzheimer’s Disease: Friend or Foe?
Does lanabecestat, a potent inhibitor of the beta-site amyloid precursor protein–cleaving enzyme 1 (BACE1), slow the progression of early Alzheimer disease (AD) and mild AD dementia?.. ..Among 1722 DAYBREAK-ALZ patients, the mean (SD) age was 72.3 (7.0) years, and 1023 of 1722 (59.4%) were women. Both studies were terminated early after futility analysis. There were no consistent, reproducible dose-related findings on primary or secondary efficacy … Continue reading Efficacy and Safety of #Lanabecestat for Treatment of Early and Mild #Alzheimer Disease
Epidemiological, preclinical, and clinical studies have suggested a role for microdose lithium in reducing Alzheimer’s disease (AD) risk by modulating key mechanisms associated with AD pathology. The novel microdose lithium formulation, NP03, has disease-modifying effects in the McGill-R-Thy1-APP transgenic rat model of AD-like amyloidosis at pre-plaque stages, before frank amyloid-β (Aβ) plaque deposition, during which Aβ is primarily intraneuronal.. During the early Aβ post-plaque stage, … Continue reading NP03, a Microdose #Lithium Formulation, Blunts Early #Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats