Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors.
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.
Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
Kaori
K
Miwa
Department of Strokology, Stroke Center, Hoshigaoka Medical Center, Osaka, Japan.
Makiko
M
Tanaka
Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
Shuhei
S
Okazaki
Department of Stroke Medicine, Kawasaki Medical University, Kurashiki, Japan.
Yoshiki
Y
Yagita
Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
Manabu
M
Sakaguchi
Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
Hideki
H
Mochizuki
Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
Kazuo
K
Kitagawa
D000368:Aged; D059168:Carotid Intima-Media Thickness; D059345:Cerebral Small Vessel Diseases / Q000097:blood* / Q000453:epidemiology* / Q000401:mortality; D003704:Dementia / Q000097:blood* / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D018709:Statistics, Nonparametric
D006710:Homocysteine
Alzheimer’s disease; cerebral small-vessel disease; dementia; estimated glomerular filtration rate; homocysteine; microbleeds; vascular dementia