Alzheimer's & Dementia : the Journal of the Alzheimer's Association

INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants...

BACKGROUND: A combination of plasma phospho-tau (p-tau), amyloid beta (Aβ)-positron emission tomography (PET), brain magnetic resonance imaging, cognitive function tests, and other biomarkers might predict future cognitive decline. This study aimed to investigate the efficacy of combining these biomarkers in predicting future cognitive stage transitions within 3 years. METHODS: Among the participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE-V) study, 49 mild cognitive impairment (MCI) and 113 cognitively unimpaired (CU) participants with Aβ-PET and brain imaging data were analyzed...

INTRODUCTION: At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias. METHODS: The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry...

INTRODUCTION: Remote, internet-based methods for recruitment, screening, and longitudinally assessing older adults have the potential to facilitate Alzheimer's disease (AD) clinical trials and observational studies. METHODS: The Brain Health Registry (BHR) is an online registry that includes longitudinal assessments including self- and study partner-report questionnaires and neuropsychological tests. New initiatives aim to increase inclusion and engagement of commonly under-included communities using digital, community-engaged research strategies...

BACKGROUND: The exploration of associations between dietary patterns and dementia-related neuroimaging markers can provide insights on food combinations that may impact brain integrity. METHODS: Data were derived from the Swedish Gothenburg H70 Birth Cohort Study (n = 610). Three dietary patterns were obtained using principal component analysis. Magnetic resonance imaging markers included cortical thickness, an Alzheimer's disease (AD) signature score, small vessel disease, and white matter microstructural integrity...

New "omic" technologies are revealing shared and distinct biological pathways within and across neurodegenerative diseases (NDDs), allowing a better understanding of endophenotypes that exceeds the boundaries of the current diagnostic criteria. Moreover, a diagnostic framework is needed that can accommodate the co-pathology and the clinical overlap and heterogeneity of NDDs. Apart from dissecting the reasons for a revolution in how we conceive NDD, this article aims to prompt a change in how we diagnose and classify NDD, drafting a general scheme for a new nosology...

INTRODUCTION: Women are more vulnerable to Alzheimer's disease (AD) than men. The entorhinal cortex (EC) is one of the earliest structures affected in AD. We identified in cognitively intact elderly different molecular changes in the EC in relation to age. METHODS: Changes in 12 characteristic molecules in relation to age were determined by quantitative immunohistochemistry or in situ hybridization in the EC. They were arbitrarily grouped into sex steroid-related molecules, markers of neuronal activity, neurotransmitter-related molecules, and cholinergic activity-related molecules...

Observational studies have shown consistently that modifiable risk factors during life are associated with increased dementia risk in old age but randomized controlled trials (RCTs) on dementia prevention evaluating the treatment of these risk factors did not find consistent effects on cognitive outcomes. The discrepancy in findings is potentially attributable to inherent differences between the two study designs. Although RCTs are the gold standard for establishing causality, designing and conducting an RCT for dementia prevention is complex...

INTRODUCTION: Genetic associations with Alzheimer's disease (AD) age at onset (AAO) could reveal genetic variants with therapeutic applications. We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations. METHODS: A genetic association study was conducted to examine ADAD AAO in 340 individuals with the PSEN1 E280A mutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic early-onset AD study and four late-onset AD studies...

INTRODUCTION: Secernin-1 (SCRN1) is a neuronal protein that co-localizes with neurofibrillary tangles in Alzheimer's disease (AD), but not with tau inclusions in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or Pick's disease. METHODS: We measured SCRN1 concentration in cerebrospinal fluid (CSF) using a novel mass spectrometric parallel reaction monitoring method in three clinical cohorts comprising patients with neurochemically characterized AD (n = 25) and controls (n = 28), clinically diagnosed Parkinson's disease (PD; n = 38), multiple system atrophy (MSA; n = 31), PSP (n = 20), CBD (n = 8), healthy controls (n = 37), and neuropathology-confirmed AD (n = 47)...

INTRODUCTION: Solanezumab is a monoclonal antibody that binds to the mid-domain of soluble amyloid β peptide. This meta-analysis evaluated the effect of low-dose solanezumab on clinical progression in three phase 3 studies. METHODS: The population comprised patients aged ≥55 years with Alzheimer's disease (AD) with mild dementia, randomized to 400 mg solanezumab or placebo every 4 weeks for 80 weeks. Frequentist mixed-model repeated-measures (MMRM) and Bayesian disease progression model (DPM) longitudinal analyses were conducted...

INTRODUCTION: Cardiorespiratory fitness (CRF) is associated with improved health and survival. Less is known about its association with Alzheimer's disease and related dementias (ADRD). METHODS: We identified 649,605 US veterans 30 to 95 years of age and free of ADRD who completed a standardized exercise tolerance test between 2000 and 2017 with no evidence of ischemia. We examined the association between five age- and sex-specific CRF categories and ADRD incidence using multivariate Cox regression models...

INTRODUCTION: Remote screening for cognitive impairment associated with Alzheimer's disease (AD) has grown in importance with the expected rise in prevalence of AD in an aging population and with new potential treatment options. METHODS: The Telephone Interview for Cognitive Status (TICS) and new telephone adaptation of the Montreal Cognitive Assessment (T-MoCA) were administered to participants independently classified through in-person clinical evaluation as cognitively normal (CN; n = 167), mild cognitive impairment (MCI; n = 25), or dementia (n = 23)...

INTRODUCTION: The objective was to analyze associations between dietary intake of multiple nutrients and altered cognitive function and/or decline. METHODS: Observational analyses of participants (n = 6334) in two randomized trials of nutritional supplements for age-related macular degeneration: Age-Related Eye Disease Study (AREDS) and AREDS2. RESULTS: In AREDS, for 4 of 38 nutrients examined, higher intake quintiles were significantly associated with decreased risk of cognitive impairment on the Modified Mini-Mental State test (<80): β-carotene, copper, docosahexaenoic acid, and insoluble fiber...

The wave of individuals impacted by dementia continues to rise rapidly as worldwide lifespan increases. Dietary strategies to slow cognitive decline and prolong time to clinical dementia remain understudied, but with potentially powerful public health consequences. Indeed, previously conducted large, randomized, placebo-controlled trials of micronutrients remain an under-leveraged resource to study changes in cognitive performance. As a motivating example, we highlight an ancillary report from the Physicians' Health Study, where subjects randomized to β-carotene (a provitamin A carotenoid) had a more attenuated change in longitudinal global cognitive performance and verbal memory, as compared to subjects randomized to placebo...

INTRODUCTION: Increased levels of sex hormones have been hypothesized to decrease Alzheimer's disease (AD) risk. We assessed the association between sex steroid hormones with AD using a Mendelian randomization (MR) approach. METHODS: An inverse-variance weighting (IVW) MR analysis was performed using effect estimates from external genome-wide association study (GWAS) summary statistics. We included independent variants (linkage disequilibrium R2  < 0...

INTRODUCTION: This systematic review evaluates the accuracy of the Montreal Cognitive Assessment (MoCA) for detecting mild cognitive impairment (MCI). METHODS: We searched MEDLINE, PSYCInfo, EMBASE, and Cochrane CENTRAL (1995-2021) for studies comparing the MoCA with validated diagnostic criteria to identify MCI in general practice. Screening, data extraction, and risk of bias assessment were performed independently, in duplicate. Pooled sensitivity and specificity for MoCA cutoffs were estimated using bivariate meta-analysis...

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder, characterized by memory deficit and dementia. AD is considered a multifactorial disorder where multiple processes like amyloid-beta and tau accumulation, axonal degeneration, synaptic plasticity, and autophagic processes plays an important role. In this study, the spatial proteomic differences in the neonatal 5xFAD brain tissue were investigated using MALDI-MSI coupled to LC-MS/MS, and the statistically significantly altered proteins were associated with AD...

INTRODUCTION: According to previous estimates, 40% of dementia cases globally may be attributed to 12 potentially modifiable risk factors. METHODS: We calculated national population attributable fractions (PAFs) for each risk factor and modeled the effects of proportional reductions in risk factor prevalence on dementia prevalence by calculating potential impact fractions (PIFs) for each factor. RESULTS: The overall adjusted PAF for all risk factors was 35...

INTRODUCTION: Dementia is highly prevalent in older Aboriginal Australians, with several modifiable risk factors. Currently, there is limited evidence on how to prevent cognitive decline in Aboriginal Australians. METHODS: Based on our Theory of Change (ToC) framework, we co-developed the Dementia risk management and prevention program for Aboriginal Australians (DAMPAA) aged over 45 years in partnership with Aboriginal community-controlled organizations (ACCOs) and Elders...