Cognitive Dispersion Is Not Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Results from the European Prevention of Alzheimer’s Dementia (EPAD) v500.0 Cohort

Abstract

Background: Cognitive dispersion, variation in performance across cognitive domains, is posited as a non-invasive and cost-effective marker of early neurodegeneration. Little work has explored associations between cognitive dispersion and Alzheimer’s disease (AD) biomarkers in healthy older adults. Even less is known about the influence or interaction of biomarkers reflecting brain pathophysiology or other risk factors on cognitive dispersion scores. Objective: The main aim of this study was to examine whether higher cognitive dispersion was associated with cerebrospinal fluid (CSF) levels of amyloid-β (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), and amyloid positivity in a cohort of older adults at various severities of AD. A secondary aim was to explore which AD risk factors were associated with cognitive dispersion scores. Methods: Linear and logistic regression analyses explored the associations between dispersion and CSF levels of Aβ42, t-tau, and p-tau and amyloid positivity (Aβ42 < 1000 pg/ml). Relationships between sociodemographics, APOE ɛ4 status, family history of dementia, and levels of depression and dispersion were also assessed. Results: Dispersion did not emerge as associated with any of the analytes nor amyloid positivity. Older (β= –0.007, SE = 0.002, p = 0.001) and less educated (β= –0.009, SE = 0.003, p = 0.009) individuals showed greater dispersion. Conclusion: Dispersion was not associated with AD pathology, but was associated with age and years of education, highlighting individual differences in cognitive aging. The use of this metric as a screening tool for existing AD pathology is not supported by our analyses. Follow-up work will determine if dispersion scores can predict changes in biomarker levels and/or positivity status longitudinally.

Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer’s Disease Biomarker-Positive Older Adults

“…Results from the few existing studies that have examined associations of IIV and AD biomarkers or neuropathology have been mixed. An autopsy study showed that higher IIV was significantly associated with more severe neurofibrillary tangle pathology and trended toward an association with more severe neuritic plaques ( Malek-Ahmadi et al, 2017 ) whereas another study found that IIV was not associated with in vivo CSF-based markers of AD pathology cross-sectionally ( Watermeyer et al, 2020 ). A unique aspect of the current study is the integration of longitudinal data, CSF AD biomarkers, and CBF.…”

“…The few studies linking IIV to brain changes have shown that greater IIV relates to faster rates of cerebral atrophy in entorhinal cortex and hippocampus at follow-up ( Bangen et al, 2019 ) and more severe neurofibrillary tangle pathology and neuritic plaques ( Malek-Ahmadi et al, 2017 ). In contrast, another recent study found that IIV was not associated with cerebrospinal fluid (CSF) based markers of amyloid ( Watermeyer et al, 2020 ). There have been no studies published to date examining baseline IIV associations with early cerebrovascular damage such as reduced cerebral blood flow (CBF) using arterial spin labeling (ASL) magnetic resonance imaging (MRI).…”

“…While some variability in domains of cognitive performance is normal, greater variability has been associated with decreased neuronal integrity ( Lovden et al, 2013 ), subcortical ischemic vascular cognitive impairment ( Richards et al, 2019 ), greater dementia incidence at follow-up ( Watermeyer et al, 2020 ), and having an AD classification ( Halliday et al, 2018 ). However, in vivo brain changes underlying IIV have received relatively limited study.…”

Personality predictors of cognitive dispersion: A coordinated analysis of data from seven international studies of older adults.

“…This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. Holland, 2018;Watermeyer et al, 2020Watermeyer et al, , 2021. We encourage researchers to extend our investigation to examine age-related compensatory strategies that may occur in response to cognitive senescence.…”

“…Importantly, estimation of within-person cognitive dispersion based on neuropsychological procedures is simple and cost-effective for clinicians (Holtzer et al, 2008). In particular, the adoption of these indices would repurpose familiar and currently available neuropsychological tools to potentially optimize their sensitivity and specificity for dementia detection (Gleason et al, 2018; Holtzer et al, 2008; Watermeyer et al, 2020), thereby relieving clinical and research groups from the pressures surrounding the implementation of novel assessment protocols, such as expertise acquisition through staff training. This may be particularly pertinent to areas of the country or world where resources for such activities are limited (e.g., developing nations).…”