Sex differences and Modifiable Dementia Risk Factors Synergistically Influence Memory over the Adult Lifespan

Abstract

INTRODUCTION: More women than men develop Alzheimer’s disease, yet women show less age-related episodic memory decline, a contradiction that may be accounted for by modifiable risk factors for dementia. METHODS: Associations between sex, modifiable dementia risk factors, and cognition were measured in a cross-sectional online sample (n = 21,840, ages 18-89). RESULTS: Across four tests of associative memory and executive functions, only a Face-Name Association task revealed sex differences in age-related decline. Men had worse associative memory than women (the equivalent of four years of aging). Each additional risk factor had the equivalent of three and a half years of aging. Men had greater age-related decline in associative memory than women among those with no to one risk factors, but multiple risk factors eliminated the female advantage. DISCUSSION: Because the relationship between dementia risk factors and age-related memory decline differs for men and women, sex-specific dementia prevention approaches are warranted.

The adverse effect of modifiable dementia risk factors on cognition amplifies across the adult lifespan

“…Although online assessment makes testing more accessible to individuals who are too busy or not capable of attending in‐person testing, the sample reflects individuals who had web literacy, access to a computer and Internet connection, and were self‐motivated to take the online test. Sex differences are expected to influence the current findings and are explored in a separate paper 39 . The use of measures ostensibly sensitive to the downstream effects of dementia risk factors was achieved by the combination of online testing (to obtain large sample sizes) and a sensitive assessment suited to detect changes in people with risk factors (e.g., distributed damage due to subtle vascular brain changes, white matter changes, and reduced reserve capacity, leading to earlier onset of clinically‐evident neurodegeneration 40 ).…”

Change in lipids before onset of dementia, coronary heart disease, and mortality: A 28‐year follow‐up Whitehall II prospective cohort study

“…Systematic reviews of trials reported some evidence that statin use in older adults at risk of vascular disease does not prevent dementia, but these trials have a short follow-up. 31,48 For cognitive function there is some evidence of greater vulnerability in women to the effect of vascular risk factors 20,21 and APOE ε4 22 ; for APOE ε4 this also extends to risk of AD. [23][24][25] Few studies have tested sex differences in the association of lipids with dementia, although most studies include sex as a covariate.…”

“…19 A recent study found that the combined impact of eight risk factors (education, hearing loss, traumatic brain injury, alcohol/substance abuse, hypertension, smoking, diabetes, and depression) on cognitive decline was greater in women than in men. 20 In women but not men a better lipid profile has been shown to predict maintenance of cognitive abilities at older ages. 21 There is also some evidence to suggest that women are more vulnerable to the deleterious effects of the apolipoprotein E (APOE) ε4 allele for cognitive outcomes, decline in episodic memory 22 and AD.…”