Vascular Health and Genetic Risk Affect Mild Cognitive Impairment Status and 4-Year Stability: Evidence From the Victoria Longitudinal Study

Objectives:

Mild cognitive impairment (MCI) is a high-risk condition for progression to Alzheimer's disease (AD). Vascular health is a key mechanism underlying age-related cognitive decline and neurodegeneration. AD-related genetic risk factors may be associated with preclinical cognitive status changes. We examine independent and cross-domain interactive effects of vascular and genetic markers for predicting MCI status and stability.

Method:

We used cross-sectional and 2-wave longitudinal data from the Victoria Longitudinal Study, including indicators of vascular health (e.g., reported vascular diseases, measured lung capacity and pulse rate) and genetic risk factors—that is, apolipoprotein E (APOE; rs429358 and rs7412; the presence vs absence of 4) and catechol-O-methyltransferase (COMT; rs4680; met/met vs val/val). We examined associations with objectively classified (a) cognitive status at baseline (not impaired congnitive (NIC) controls vs MCI) and (b) stability or transition of cognitive status across a 4-year interval (stable NIC–NIC vs chronic MCI–MCI or transitional NIC–MCI).

Results:

Using logistic regression, indicators of vascular health, both independently and interactively with APOE 4, were associated with risk of MCI at baseline and/or associated with MCI conversion or MCI stability over the retest interval.

Discussion:

Several vascular health markers of aging predict MCI risk. Interactively, APOE 4 may intensify the vascular health risk for MCI.

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