Biomarkers.

Background: Stronger default mode (DMN) and bilateral frontoparietal control network (FPCN) resting-state functional connectivity are associated with reduced β-amyloid (Aβ)-related cognitive decline in cognitively unimpaired older adults, who were predominantly Aβ negative. This suggests that these networks might support cognitive resilience in the face of early AD pathology but it remains unclear whether these effects are apparent in preclinical AD. We investigated whether left-FPCN, right-FPCN, and DMN connectivity moderated the effect of Aβ on cognitive decline using a large multi-site dataset from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study.

Biomarkers.

Background: Virtually all adults with Down Syndrome(DS) show Alzheimer's disease(AD)-related pathologic change by the age of 40 years. While sex differences in Aβ-dependent tauopathy are apparent during early sporadic AD, sex differences in the DS population remain under-investigated. Moreover, menopause onset occurs earlier in the DS population (45 years), and it remains unknown whether menopause status and hormone therapy(HT) exposure influences Aβ-dependent tauopathy in women with DS.

Developing Topics.

Background: Executive dysfunction is a hallmark clinical feature of frontotemporal degeneration (FTD). Genome-wide association studies have identified genetic variants, and resulting polygenic scores (PGS), related to executive function (EF) in population studies. We evaluated whether EF-PGS correlates with differential rates of cognitive decline in FTD.

Developing Topics.

Background: The residual approach has found wide application in researching cognitive resilience, a phenomenon conceptually understood as cognitive performance being better-than-typical for an individual, despite apparent AD pathology. The standard residual approach extracts information about an individual's resilience from the residuals of a linear model predicting cognition. This approach is subject to several limiting assumptions.

Developing Topics.

Background: Emerging evidence relates neighborhood deprivation to cognitive decline and neurodegeneration but this is understudied in frontotemporal degeneration (FTD). We assessed the association of neighborhood deprivation with survival in 147 individuals with behavioral-variant FTD (bvFTD).

Method: Neighborhood deprivation was measured using the Area Deprivation Index (ADI), a national percentile ranking of deprivation based on income, education, employment, and housing quality.