Abstract
BackgroundInterindividual differences in cognitive reserve (CR) are associated with complex and dynamic clinical phenotypes observed in cognitive impairment and dementia. We tested whether (1) CR early in life (E-CR; measured by education and IQ), (2) CR later in life (L-CR; measured by occupation), and (3) CR panel (CR-P) with the additive effects of E-CR and L-CR, act as moderating factors between baseline ventricular size and clinical dementia severity at baseline and across 2 years. We further examined whether this moderation is differentially represented by sex.MethodsWe examined a longitudinal model using patients (N = 723; mean age = 70.8 ± 9.4 years; age range = 38–90 years; females = 374) from the Sunnybrook Dementia Study. The patients represented Alzheimer’s disease (n = 439), mild cognitive impairment (n = 77), vascular cognitive impairment (n = 52), Lewy body disease (n = 30), and frontotemporal dementia (n = 125). Statistical analyses included (1) latent growth modeling to determine how clinical dementia severity changes over 2 years (measured by performance on the Dementia Rating Scale), (2) confirmatory factor analysis to establish a baseline E-CR factor, and (3) path analysis to predict dementia severity. Baseline age (continuous) and Apolipoprotein E status (ɛ4−/ɛ4+) were included as covariates.ResultsThe association between higher baseline ventricular size and dementia severity was moderated by (1) E-CR and L-CR and (2) CR-P. This association was differentially represented in men and women. Specifically, men in only the low CR-P had higher baseline clinical dementia severity with larger baseline ventricular size. However, women in the low CR-P showed the (1) highest baseline dementia severity and (2) fastest 2-year decline with larger baseline ventricular size.ConclusionsClinical dementia severity associated with ventricular size may be (1) selectively moderated by complex and additive CR networks and (2) differentially represented by sex.Trials registrationClinicalTrials.gov, NCT01800214. Registered on 27 February 2013.
Highlights
Interindividual differences in cognitive reserve (CR) are associated with complex and dynamic clinical phenotypes observed in cognitive impairment and dementia
We examine whether the association between ventricular size and clinical dementia severity [21,22,23] is differentially moderated by CR in men and women across a large, heterogeneous sample of patients with cognitive impairment and dementia
Our finding demonstrates that the additive effects of environment throughout the life course (E-CR) and Later-life cognitive reserve (L-CR) may differentially contribute to the complex clinical manifestations observed in dementia
Summary
Interindividual differences in cognitive reserve (CR) are associated with complex and dynamic clinical phenotypes observed in cognitive impairment and dementia. The spectrum of neurodegenerative pathologies in the aging brain in combination with cardiovascular risk factors has led to an increased prevalence and diagnosis of mixed neurodegenerative diseases (combination of proteinopathies and vasculopathies) [1]. A recent review examined 12 communitybased neuropathology studies and identified that the frequency of Alzheimer’s disease (AD) pathology was 19–67%, Lewy body pathology was 6–39%, vascular pathologies was 28–70%, and mixed pathologies was 10–74% [2]. Combinations of neurodegenerative (e.g., proteinopathies) and non-neurodegenerative (e.g., metabolic-nutritional, vascular) pathologies may depict the multifaceted clinical manifestations observed in patients with dementia. In addition to the heterogeneity and complexity of pathologies, variability and differences in life experiences may further complicate the course of cognitive decline and clinical dementia severity. Identifying modifiable risk and protective proxies of cognitive reserve (CR) may lead to personalized interventions for those most at risk of accelerated cognitive impairment [3].
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