Clinical dementia severity associated with ventricular size is differentially moderated by cognitive reserve in men and women

Alzheimers Res Ther. 2018 Sep 5;10(1):89. doi: 10.1186/s13195-018-0419-2.


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:, NCT01800214 . Registered on 27 February 2013.

Keywords: Cognitive impairment; Cognitive reserve; Dementia; Sex; Sunnybrook Dementia Study; Ventricular size.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cerebral Ventricles / pathology*
  • Cognitive Reserve*
  • Dementia / pathology*
  • Dementia / psychology*
  • Disease Progression
  • Female
  • Humans
  • Intelligence
  • Intelligence Tests
  • Male
  • Middle Aged
  • Occupations
  • Severity of Illness Index

Associated data