The prevalence of mild cognitive impairment in diverse geographical and ethnocultural regions: The COSMIC Collaboration

Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P = .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally

[Accepted Manuscript] Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study.

Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. Atrophy rates are pathologically increased up to seven years before &quot;expected onset&quot;. During this period, atrophy rates may be useful for inclusion and tracking of disease progression

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Semantic item-level metrics relate to future memory decline beyond existing cognitive tests in older adults without dementia

Objective: A critical need persists to develop sensitive and high-access cognitive markers for early detection of dementia. Among older adults without dementia, we investigated if item-level metrics of semantic fluency related to episodic memory decline above and beyond traditional neuropsychological measures and total fluency score. Method: Participants were drawn from the community-based WHICAP cohort (N=583 English speakers, mean age=76.3±6.8) followed up to 5 visits across up to 11 years. We investigated the distribution of seven semantic fluency metrics—one traditional, four psycholinguistic, two sequential—by age, sex/gender, race, education, APOE e4 status, and subjective cognitive complaints. Subsequently, associations of each fluency metric with memory performance and decline over time were investigated using latent growth curve models covaried for age and recruitment wave. Additional models adjusted for other standard neuropsychological tests, and tested for moderation by education and race. Results: Both traditional and psycholinguistic metrics were associated with memory decline in the first set of models. When adjusting for other cognitive tests, however, only psycholinguistic metrics remained associated—even when covarying for total fluency score. A multiple-group modeling approach showed that the relationship of semantic fluency metrics with memory decline did not differ across race or education. Conclusions: Item-level data hold a wealth of information with potential to reveal subtle cognitive decline among older adults without dementia beyond traditional neuropsychological measures. Implementation of psycholinguistic metrics may point to cognitive tools that have better prognostic value or are more sensitive to cognitive change in the context of clinical trials or observational studies

Offspring Study of Racial and Ethnic Disparities in Alzheimer’s Disease: Objectives and Design

The Offspring Study of Racial and Ethnic Disparities in Alzheimer’s Disease began in 2017 to identify biological and sociocultural mechanisms of disparities in cognitive function among middle-aged people with and without a parent with Alzheimer's Disease (AD). This article outlines the objectives and design of this prospective cohort study aimed at advancing the understanding of risk factors among middle aged offspring in order to clarify pathways to AD, and provides background on recruitment and retention of this diverse cohort