Association between CAIDE risk score and episodic memory in middle-aged females: The impact of spontaneous menopause

There is growing evidence that postmenopause is associated with episodic memory decline in some females. Although midlife vascular risk factors are established predictors of brain health, it is unclear whether episodic memory decline at postmenopause is related to vascular risk, and whether such effects affect specific mnemonic functions (e.g. recollective processing vs. novelty detection). This study investigated whether vascular risk, measured by the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score, predicts episodic memory in middle-aged females at pre- and post-menopause. Eighty-five cognitively unimpaired females (42 premenopausal, 43 postmenopausal) aged 39.5 to 65.1 years completed easy (low encoding load) and hard (high encoding load) versions of a face-location episodic memory task. Outcome measures were spatial source retrieval (correct source accuracy; CS) and detection of novel stimuli (correct rejections; CR). Linear-mixed models (LMMs) tested menopause group effects on CS and CR, while separate LMMs stratified by menopause status assessed whether CAIDE score predicted memory performance in each group. Results indicated that postmenopausal females performed worse than premenopausal females in both CS (β = 0.08, p < 0.001) and CR (β = 0.05, p = 0.011), with postmenopausal females more sensitive to task difficulty in CS. Higher CAIDE scores were associated with poorer CS accuracy in postmenopausal females only (β = -0.14, p = 0.009), with no effect on CR. These findings highlight the significance of vascular risk in episodic memory decline and emphasize the role of reproductive status in midlife cognition.