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Clinical dementia severity associated with ventricular size is differentially moderated by cognitive reserve in men
Shraddha Sapkota1, Joel Ramirez2, Donald T Stuss2,3,4,5
1Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, M6-192, Toronto, ON, M4N 3M5, Canada. shraddha.sapkota@sunnybrook.ca.
Background:
Interindividual 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.
Methods:
We 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.
Results:
The 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.
Conclusions:
Clinical dementia severity associated with ventricular size may be (1) selectively moderated by complex and additive CR networks and (2) differentially represented by sex.
Trials Registration:
ClinicalTrials.gov, NCT01800214 . Registered on 27 February 2013.
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