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Midlife Risk Factors for Subtypes of Dementia: A Nested Case-Control Study in Taiwan

From the Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei (CJC); the Department of Neurology, National Taiwan University Hospital and National Taiwan University, Taipei (PKY); Institute of Health and Welfare Policy, National Yang-Ming University, Taipei (SCW); Section of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei (CSL); Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung (CWL); Department of Neurology, National Yang-Ming University School of Medicine, and The Neurological Institute, Taipei Veterans General Hospital, Taipei (HCL); Department of Neurology, Kaohsiung Medical University, Kaohsiung (CKL); Department of Neurology, Wei Gong Memorial Hospital, Miaoli (CHC); Department of Neurology, Taipei City Hospital, Chung-Hsiao Branch, Taipei (CSH); Department of Neurology, ChiaYi Christian Hospital, Chiayi (SFS); Department of Neurology, Tri-Service General Hospital and National Defense Medical Center, Taipei (YDH); Department of Psychiatry, Kaohsiung Medical University, and Tsyr-Huey (Loving) Mental Hospital, Kaohsiung (CCC); Department of Psychiatry, Mackay Memorial Hospital, Taipei (SIL); Department of Neurology, Taipei City Hospital, Ren-Ai Branch, Taipei (SHY); Department of Neurology, Buddhist Dalin Tzu Chi General Hospital, Chiayi (CSF); Department of Neurology, Ming Jong Hospital, Pingtung (SFC); Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei (SLY); and the Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, and Genomics Research Center, Academia Sinica, Taipei (CJC); Taiwan.

Objective: To identify the midlife risk factors for subtypes of dementia newly developed later in life.

Methods: A nested case-control study was conducted on 157 demented cases and 628 comparison cases selected from 40,636 men and women who were enrolled from 1982 to 1992. Four comparison cases were frequency-matched on age, time at enrollment (within 6 months), gender, and residential township. Midlife risk factors included vascular risk factors (body mass index [BMI], total cholesterol, total triglycerides, blood glucose, cerebrovascular accident [CVA] history, diabetes mellitus history, and hypertension history), cigarette smoking, and alcohol consumption. Dementia assessments were ascertained through the computerized data linkage from National Health Insurance Database from 2000 to 2002 and clinically confirmed by neurologists or psychiatrists. Conditional logistic regression analysis was used to estimate the matched odds ratio (OR) and its 95% confidence intervals (CI) for each risk factor.

Results: A J-shaped relationship was observed between BMI (kg/m²) and dementia. The multivariate-adjusted ORs (95% CI) of developing dementia were 1.84 (1.02–3.33), 1.87 (1.08–3.23) and 2.44 (1.39–4.28), respectively, for BMIs of <20.5, 23.0–25.4, 25.5 compared with a BMI of 20.5–22.9 as the referent group (OR = 1.0). Similar findings were observed for Alzheimer disease (AD) and vascular dementia (VaD). The association between obesity (BMI 25.5) and both AD and VaD was statistically significant among cigarette smokers but not among nonsmokers. Additionally, history of CVA was a significant risk factor for VaD, but not for AD.

Conclusion: Being underweight, being overweight, and a cerebrovascular accident in midlife may increase the risk of dementia in late life.

Key Words: Alzheimer disease • vascular dementia • body mass index • risk factors • epidemiology

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