INTRODUCTION Reliable estimates of time from diagnosis until institutionalization and death in people with dementia from routine nationally representative databases are lacking. METHODS We selected 9230 people with dementia and 24,624 matched controls from family physicians' electronic records linked with national administrative databases to analyze time until institutionalization and death and associated

INTRODUCTION We aim to determine racial disparities and their modifying factors in risk for Alzheimer's disease (AD) dementia among cognitively normal individuals 65 years or older. METHODS Longitudinal data from the National Alzheimer's Coordinating Center Uniform Data Set on 1229 African Americans (AAs) and 6679 whites were analyzed for the risk of AD using competing risk models with death as a competing

INTRODUCTION We evaluated the impact of deprescribing acetylcholinesterase inhibitors (AChEIs) on aggressive behaviors and incident antipsychotic use in nursing home (NH) residents with severe dementia. METHODS We conducted a retrospective study of Medicare claims, Part D, Minimum Data Set for NH residents aged 65+ with severe dementia receiving AChEIs in 2016. Aggressive behaviors were measured using

INTRODUCTION Developing cross-validated multi-biomarker models for the prediction of the rate of cognitive decline in Alzheimer's disease (AD) is a critical yet unmet clinical challenge. METHODS We applied support vector regression to AD biomarkers derived from cerebrospinal fluid, structural magnetic resonance imaging (MRI), amyloid-PET and fluorodeoxyglucose positron-emission tomography (FDG-PET)

INTRODUCTION Clinical Alzheimer's disease (AD) and dementia with Lewy bodies often have mixed AD and Lewy pathology, making it difficult to delineate risk factors. METHODS Six risk factors for earlier dementia onset due to autopsy-confirmed AD (n = 647), mixed AD and Lewy body disease (AD + LBD; n = 221), and LBD (n = 63) were entered into multiple linear regressions using data from the National Alzheimer's

INTRODUCTION Spatial navigation deficits are observed in Alzheimer's disease cross-sectionally, but prediction of longitudinal clinical decline has been less examined. METHODS Cognitive mapping (CM) was assessed in 95 participants and route learning (RL) was assessed in 65 participants at baseline. Clinical progression over an average of 4 to 5 years was assessed using the clinical dementia rating

INTRODUCTION We evaluated the clinical profile of the orexin receptor antagonist suvorexant for treating insomnia in patients with mild-to-moderate probable Alzheimer's disease (AD) dementia. METHODS Randomized, double-blind, 4-week trial of suvorexant 10 mg (could be increased to 20 mg based on clinical response) or placebo in patients who met clinical diagnostic criteria for both probable AD dementia

INTRODUCTION Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine the associations between MBI and Alzheimer's disease (AD) biomarkers in asymptomatic elderly individuals. METHODS Ninety-six cognitively normal elderly individuals underwent MRI, [18 F]AZD4694 β-amyloid-PET, and [18 F]MK6240 tau-PET. MBI was assessed using

INTRODUCTION Familial frontotemporal lobar degeneration (f-FTLD) due to autosomal dominant mutations is an important entity for developing treatments for FTLD. The Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) longitudinal studies were designed to describe the natural history of f-FTLD

INTRODUCTION Cerebrospinal fluid (CSF) biomarkers can identify individuals with Alzheimer's disease (AD) pathology (eg, amyloid plaques, neurofibrillary tangles), but defined analyte cut-points using high-throughput automated assays are necessary for general clinical use. METHODS CSF amyloid β42 peptide (Aβ42), t-tau, and t-tau/Aβ42 were quantified by the Lumipulse platform in two test cohorts (A/B:

INTRODUCTION Reduced hippocampal volume is associated with late-life cognitive decline, but prior studies have not determined whether this association persists after accounting for Alzheimer's disease (AD) and other neuropathologies. METHODS Participants were 531 deceased older adults from community-based cohort studies of aging who had undergone annual cognitive evaluations. At death, brain tissue

INTRODUCTION Leisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD). METHODS A total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed

INTRODUCTION The PSENs/APP mutation distribution in Chinese patients with familial Alzheimer's disease (FAD) remains unclear. We aimed to analyze the genetic features of Chinese FAD pedigrees with and without PSENs/APP mutations. METHODS In total, 1330 patients with Alzheimer's disease (AD) or mild cognitive impairment in 404 pedigrees were enrolled from the Chinese Familial Alzheimer's Disease Network

INTRODUCTION Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified

The last decade has seen a substantial increase in research focused on the identification, development, and validation of diagnostic and prognostic retinal biomarkers for Alzheimer's disease (AD). Sensitive retinal biomarkers may be advantageous because they are cost and time efficient, non-invasive, and present a minimal degree of patient risk and a high degree of accessibility. Much of the work in

INTRODUCTION The aim is to test whether adding a simple physical test such as walking speed (WS) to the neuropsychological assessment increases the predictive ability to detect dementia. METHODS The 2546 dementia-free people from the SNAC-K study were grouped into four profiles: (1) healthy profile; (2) isolated cognitive impairment, no dementia (CIND, scoring 1.5 standard deviation below age-specific

INTRODUCTION We compared genetic variants between Alzheimer's disease (AD) and two age-related cancers-breast and prostate -to identify single-nucleotide polymorphisms (SNPs) that are associated with inverse comorbidity of AD and cancer. METHODS Bayesian multinomial regression was used to compare sex-stratified cases (AD and cancer) against controls in a two-stage study. A ±500 KB region around each

INTRODUCTION Although some members of families with autosomal dominant Alzheimer's disease mutations learn their mutation status, most do not. How knowledge of mutation status affects clinical disease progression is unknown. This study quantifies the influence of mutation awareness on clinical symptoms, cognition, and biomarkers. METHODS Mutation carriers and non-carriers from the Dominantly Inherited

INTRODUCTION Numerous results suggest the implication of infectious agents in the onset of Alzheimer's disease (AD). METHODS In the Bordeaux-3C prospective cohort, we assessed the impact of herpes simplex virus type 1 (HSV-1) infection on the incidence of AD according to apolipoprotein E (APOE) status, a genetic susceptibility factor. Cox models were performed to estimate the 10-year risk of AD associated

INTRODUCTION We created global rating scoring rules for the CDR® plus NACC FTLD to detect and track early frontotemporal lobar degeneration (FTLD) and to conduct clinical trials in FTLD. METHODS The CDR plus NACC FTLD rating was applied to 970 sporadic and familial participants from the baseline visit of Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)/Longitudinal Evaluation

INTRODUCTION The Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) consortia are two closely connected studies, involving multiple North American centers that evaluate both sporadic and familial frontotemporal dementia (FTD) participants and study longitudinal changes. METHODS We screened

INTRODUCTION We investigated plasma proteomic markers of astrocytopathy, brain degeneration, plasticity, and inflammation in sporadic early-onset versus late-onset Alzheimer's disease (EOAD and LOAD). METHODS Plasma was analyzed using ultra-sensitive immuno-based assays from 33 EOAD, 30 LOAD, and 36 functionally normal older adults. RESULTS Principle component analyses identified 3 factors: trophic

INTRODUCTION This clinical trial evaluates the efficacy and safety of a 6-week course of daily neuroAD™ therapy. METHODS 131 subjects between 60 and 90 years old, unmedicated for Alzheimer's disease (AD), or on stable doses of an acetylcholinesterase inhibitor and/or memantine, with Mini-Mental State Examination scores between 18 and 26, clinical dementia rating scale scores of 1 or 2, enrolled for

INTRODUCTION Blood-brain barrier (BBB) breakdown is an early independent biomarker of human cognitive dysfunction, as found using gadolinium (Gd) as a contrast agent. Whether Gd accumulates in brains of individuals with an age-dependent BBB breakdown and/or mild cognitive impairment remains unclear. METHODS We analyzed T1-weighted magnetic resonance imaging (MRI) scans from 52 older participants with

INTRODUCTION Preventing dementia, or modifying disease course, requires identification of presymptomatic or minimally symptomatic high-risk individuals. METHODS We used longitudinal electronic health records from two large academic medical centers and applied a validated natural language processing tool to estimate cognitive symptomatology. We used survival analysis to examine the association of cognitive

INTRODUCTION We previously characterized associations between brain imaging measurements of amyloid-β (Aβ) plaque burden and apolipoprotein E (APOE) ε4 gene dose in a small number of cognitively unimpaired late-middle-aged APOE ε4 homozygotes (HMs), heterozygotes (HTs), and noncarriers (NCs). We now characterize cross-sectional Aβ plaque, tau tangle, and cortical atrophy (neurodegeneration) measurements

INTRODUCTION Some Alzheimer's disease biomarker studies found amyloid changes 20 years or more in advance of expected symptoms, while cognitive changes lagged for more than a decade, but this apparent lag might reflect the sensitivities of the biomarker and cognitive assays used. How far in advance of incident amnestic mild cognitive impairment (MCI) does cognition begin to decline? METHODS Longitudinal

INTRODUCTION Observational studies have suggested that light-to-moderate alcohol consumption decreases the risk of Alzheimer's disease, but it is unclear if this association is causal. METHODS Two-sample Mendelian randomization (MR) analysis was used to examine whether alcohol consumption, alcohol dependence, or Alcohol Use Disorder Identification Test (AUDIT) scores were causally associated with the

Introduction Relationship between age and dementia at extreme old ages is still an open question, yet population-based studies in this high-risk age segment are rare. Methods The Monzino 80-plus is a population-based study among residents 80 years and older in the Varese province, Italy. Of 1371 eligible individuals, 1294 (94.4%), of whom 64 are centenarians, were included in the incidence study. Results

INTRODUCTION To date, the clinical relevance of comorbid amyloid-β (Aβ) pathology in patients with vascular cognitive disorders (VCD) is largely unknown. METHODS We included 218 VCD patients with available cerebrospinal fluid Aβ42 levels. Patients were divided into Aβ+ mild-VCD (n = 84), Aβ- mild-VCD (n = 68), Aβ+ major-VCD (n = 31), and Aβ- major-VCD (n = 35). We measured depression with the Geriatric

INTRODUCTION The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys

INTRODUCTION Comparison of tau (flortaucipir) positron emission tomography (FTP-PET) to autopsy is important to demonstrate the relationship of FTP-PET to neuropathologic findings. METHODS Autopsies were performed on 26 participants who had antemortem FTP-PET. FTP-PET standardized uptake value ratios (SUVRs) were compared to autopsy diagnoses and Braak tangle stage. Quantitative tau burden was compared

INTRODUCTION The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations. METHODS We examined cognitive performance, behavioral ratings, and brain volumes from the first

INTRODUCTION Frontotemporal dementia disorders (FTDs) are heterogeneous phenotypical behavioral and language disorders usually associated with frontal and/or temporal lobe degeneration. We investigated their incidence in a population-based cohort. METHODS Using a records-linkage system, we identified all patients with a diagnostic code for dementia in Olmsted County, MN, 1995-2010, and confirmed the

INTRODUCTION Apolipoprotein E (APOE) status may modify the risk of postoperative delirium conferred by inflammation. METHODS We tested whether APOE modifies the established association between C-reactive protein (CRP) and delirium incidence, severity, and duration in 553 noncardiac surgical patients aged 70 and older. High postoperative plasma CRP (≥234.12 mg/L) was defined by the highest sample-based

INTRODUCTION Demonstrating the "clinical meaningfulness" of slowing early cognitive decline in clinically normal (CN) older adults with elevated amyloid-β (Aβ+) is critical for Alzheimer's disease secondary prevention trials and for understanding early cognitive progression. METHODS Cox regression analyses were used to determine whether 3-year slopes on the preclinical Alzheimer's cognitive composite

Hispanics/Latinos are the largest ethnic/racial group in the United States and at high risk for Alzheimer's disease and related dementia (ADRD). Yet, ADRD among diverse Latinos is poorly understood and disparately understudied or unstudied compared to other ethnic/racial groups that leave the nation ill-prepared for major demographic shifts that lay ahead in coming decades. The primary purpose of this

INTRODUCTION We estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos. METHODS Middle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50-86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging-Alzheimer's Association diagnostic criteria. RESULTS The overall

INTRODUCTION Some models of therapy for neurodegenerative diseases envision starting treatment before symptoms develop. Demonstrating that such treatments are effective requires accurate knowledge of when symptoms would have started without treatment. Familial frontotemporal lobar degeneration offers a unique opportunity to develop predictors of symptom onset. METHODS We created dementia risk scores

INTRODUCTION Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. METHODS Ninety-three mutation carriers with no symptoms or minimal/questionable

Several concepts, which in the aggregate get might be used to account for “resilience” against age- and disease-related changes, have been the subject of much research. These include brain reserve, cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts

Introduction Detecting cognitive impairment in diverse, health disparities communities is an urgent health care priority. Methods The Brooklyn Cognitive Impairments in Health Disparities Pilot Study investigated quantitative aspects and liking of a computerized cognitive performance assessment, Cognigram, among individuals ≥ 40 years in traditional and nontraditional primary care settings. Results

INTRODUCTION The effect of comorbid cardiometabolic diseases (CMDs), including diabetes, heart diseases, and stroke, on dementia remains unclear. METHODS A cohort of 2648 dementia-free adults aged ≥60 years was followed up for 12 years. An active lifestyle was defined in accordance with the engagement in leisure activities and/or a social network. Cox models were used in data analysis. RESULTS The

Development of disease-modifying treatments for Alzheimer's disease (AD) has been challenging, with no drugs approved to date. The failures of several amyloid-targeted programs have led many to dismiss the amyloid beta (Aβ) hypothesis of AD. An antiamyloid antibody aducanumab recently showed modest but significant efficacy in a phase 3 trial, providing important validation of amyloid as a therapeutic

INTRODUCTION The levels and distribution of amyloid deposits in the brain does not correlate well with Alzheimer's disease (AD) progression. Therefore, it is likely that amyloid precursor protein and its proteolytic fragments other than amyloid b (Ab) contribute to the onset of AD. METHODS We developed a sensitive assay adapted to the detection of C99, the direct precursor of b-amyloid. Three postmortem

INTRODUCTION Multidomain intervention for Alzheimer's disease (AD) risk reduction is an emerging therapeutic paradigm. METHODS Patients were prescribed individually tailored interventions (education/pharmacologic/nonpharmacologic) and rated on compliance. Normal cognition/subjective cognitive decline/preclinical AD was classified as Prevention. Mild cognitive impairment due to AD/mild-AD was classified