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J Alzheimers Dis. 2016;49(2):503-13. doi: 10.3233/JAD-150458.

Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors.

Author information

1
Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
2
Department of Strokology, Stroke Center, Hoshigaoka Medical Center, Osaka, Japan.
3
Department of Stroke Medicine, Kawasaki Medical University, Kurashiki, Japan.
4
Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.

Abstract

BACKGROUND:

Homocysteine has been identified as a potential risk factor for stroke, cerebral small-vessel diseases (SVD), and dementia.

OBJECTIVE:

The present study aimed to investigate the predictive value of homocysteine levels on incident dementia while simultaneously controlling for MRI findings and vascular risk factors.

METHODS:

Within a Japanese cohort of participants with vascular risk factors in an observational study, we evaluated the association between baseline total homocysteine (tHcy) levels (per 1 μmol/L and the tertile of tHcy), the prevalence of MRI-findings at baseline, and incident all-cause dementia. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities, and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tHcy and each of MRI findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between tHcy and dementia.

RESULTS:

In the 643 subjects (age: 67.2 ± 8.4 years, male: 59% ; education: 12.9 ± 2.6 years), multivariable analyses adjusted for several potential confounders, including estimated glomerular filtration rate (eGFR) and intima-media thickness, showed that highest tHcy tertile was associated with lacunas, CMBs, and strictly deep CMBs. During the mean 7.3-year follow-up (range: 2-13), 47 patients were diagnosed with dementia (Alzheimer's disease: 24; vascular dementia: 18; mixed-type: 3; other: 2). After adjusting for age, gender, APOE ɛ4, education, BMI, MMSE, hypertension, cerebrovascular events, eGFR, and MRI-findings, tHcy level (hazard ratios [HR]: 1.08, p = 0.043) and the highest tertile of tHcy (HR: 2.50, p = 0.047) for all-cause dementia remained significant.

CONCLUSIONS:

Our results provide additional evidence of tHcy that contributes to increased susceptibility to dementia risk.

KEYWORDS:

Alzheimer’s disease; cerebral small-vessel disease; dementia; estimated glomerular filtration rate; homocysteine; microbleeds; vascular dementia

PMID:
26484913
DOI:
10.3233/JAD-150458
[Indexed for MEDLINE]

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