Greater subjective cognitive decline severity is associated with worse memory performance and lower entorhinal cerebral blood flow in healthy older adults

Abstract

Objective: Subjective cognitive decline (SCD) is a potential early risk marker for Alzheimer’s disease (AD), but its utility may vary across individuals. We investigated the relationship of SCD severity with memory function and cerebral blood flow (CBF) in areas of the middle temporal lobe (MTL) in a cognitively normal and overall healthy sample of older adults. Exploratory analyses examined if the association of SCD severity with memory and MTL CBF was different in those with lower and higher cardiovascular disease (CVD) risk status. Methods: Fifty-two community-dwelling older adults underwent magnetic resonance imaging, neuropsychological testing, and were administered the Everyday Cognition Scale (ECog) to measure SCD. Regression models investigated whether ECog scores were associated with memory performance and MTL CBF, followed by similar exploratory regressions stratified by CVD risk status (i.e., lower vs higher stroke risk). Results: Higher ECog scores were associated with lower objective memory performance and lower entorhinal cortex CBF after adjusting for demographics and mood. In exploratory stratified analyses, these associations remained significant in the higher stroke risk group only. Conclusions: Our preliminary findings suggest that SCD severity is associated with cognition and brain markers of preclinical AD in otherwise healthy older adults with overall low CVD burden and that this relationship may be stronger for individuals with higher stroke risk, although larger studies with more diverse samples are needed to confirm these findings. Our results shed light on individual characteristics that may increase the utility of SCD as an early risk marker of cognitive decline.

Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5

“…Reduction in CBF, as one of the early symptoms of AD/ADRD has been observed in numerous human and animal models of the disease [ 1 , 2 , 41 ]. The strong correlation between the severity of brain hypoperfusion and the extent of cognitive deficits [ 3 , 4 ] underscores the importance of studying this phenomenon. Understanding the underlying mechanisms of impaired vascular reactivity and CBF reduction is essential for the development of effective interventions and therapies to prevent or delay cognitive decline in AD/ADRD.…”

“…Recent studies have provided evidence suggesting that brain hypoperfusion, a condition characterized by a reduction in cerebral blood flow (CBF), can contribute to neurodegeneration, leading to cognitive impairments in individuals with Alzheimer’s Disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) [ 1 , 2 ]. Human studies have identified a strong correlation between the severity of CBF reduction and the extent of cognitive deficits, highlighting the importance of addressing CBF reduction as one of the early symptoms of AD/ADRD [ 3 , 4 ]. Despite the significant attention on the impact of CBF reduction on cognitive function and brain pathology in AD/ADRD, the genetic, molecular, and cellular mechanisms underlying this relationship remain poorly understood.…”