Abstract 224: Increased Total Homocysteine Levels Are Associated With the Risk of Dementia Independently of Cerebral Small-vessel Disease

Abstract

Objectives: Increased serum total homocysteine (tHcy) levels have been associated with not only vascular injury but also dementia. However, given an association between Hcy and vascular injury, such as cerebral small-vessel disease (SVD) or renal impairment, to what extent Hcy would impact future dementia beyond these confouders is unknown. We assessed the predictive value of tHcy levels with the risk of dementia in patients with vascular risk factors, when controlling for the MRI-findings and renal imapirment. Methods: Within a Japanese cohort of partients with vascular risk factors in an observational study from 2001, we evaluated the association between tHcy levels at baseline, defined as a continuous variable (per 1 μmol/L) and as a categorical variable (the tertile of tHcy), the prevalence of MRI-findings, and incident all-cause dementia during follow-up. Baseline brain MRI was used to determine SVD (lacuna, white matter hyperintensities and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy). Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOEε4 allele, educational level, cerebrovascular events, estimated glomerular filtration rate (eGFR), vascular risk factors, and MRI-findings. Results: Of the 643 subjects (mean:67.2±8.4years, male:59%, 12.9±2.6years of schooling), in multivariable analyses adjusted for age, sex, hypertension, cerebrovascular events, eGFR, and intima-media thickness, the highest tHcy tertile (vs lowest) were associated with lacuna, CMBs and strictly deep CMBs, respectively. During the mean 7.3-year follow-up (range:3-13), 47 incident dementia patients (Alzheimer’s disease:24; vascular dementia:18; mixed-type:3; other:2) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, eGFR, and MRI-findings, tHcy level or the highest tertile of tHcy for all-cause dementia remained significant, respectively (relative risk [RR]1.09: p=0.02, RR;2.59: p=0.021). Conclusions: Our results provide additional evidence of Hcy that leads to increased susceptibility to the risk of dementia, suggesting that this association may be mediated by independent mechanisms.