Body mass index and risk of dementia: Analysis of individual-level data from 1.3 million individuals

Introduction Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects. Methods We examined this hypothesis in 1,349,857 dementia-free participants from 39 cohort studies. BMI was assessed at baseline. Dementia was ascertained at follow-up using linkage to electronic health records (N = 6894). We assumed BMI is little affected by preclinical dementia when assessed decades before dementia onset and much affected when assessed nearer diagnosis. Results Hazard ratios per 5-kg/m2 increase in BMI for dementia were 0.71 (95% confidence interval = 0.66–0.77), 0.94 (0.89–0.99), and 1.16 (1.05–1.27) when BMI was assessed 10 years, 10-20 years, and >20 years before dementia diagnosis. Conclusions The association between BMI and dementia is likely to be attributable to two different processes: a harmful effect of higher BMI, which is observable in long follow-up, and a reverse-causation effect that makes a higher BMI to appear protective when the follow-up is short.


Finnish Twin Cohort (FTC) study, Finland
The older Finnish Twin Cohort study is a longitudinal study of all Finnish same-sex twins born before 1958. At the baseline in 1975, a postal questionnaire survey consisting of questions on health and health-related behaviors was conducted. The mean age of the participants was 36.3 (range 18.3 to 95.9) years at the start of follow-up May 1, 1976. Data for self-reported height and weight were available for 12,630 men and 13,184 women resident in Finland. Responses and returning completed questionnaire were considered as consent in postal questionnaire data collection in 1975; the study was approved by the National Board of Health. The use of the cohort for register follow-up studies has been approved by the Ethical committee of the Department of Public Health, University of Helsinki. Data and permission for use of cause of death data were obtained from Statistics Finland.

Health and Social Support (HeSSup), Finland
The Health and Social Support (HeSSup) study is a prospective cohort study of a stratified random sample of the Finnish population in the following four age groups: 20-24, 30-34, 40-44, and 50-54. The participants were identified from the Finnish population register and posted an invitation to participate, along with a baseline questionnaire, in 1998. A total of 16 666 had data on BMI from self-reported height and weight and were thus eligible for our meta-analyses. The Turku University Central Hospital Ethics Committee approved the study. Data from Gazel, WOLF-S, WOLF-N, and HeSSup were pooled to achieve sufficient case numbers (labelled IPD-Work other). Participants were linked to drug reimbursement, hospitalisation and death registers. Dementia was defined using ICD-10, codes F00, F01, F02, F03, G30 and G31 (31.0, 31.

Health and Retirement Study (HRS), USA
The Health and Retirement Study (HRS) is a leading source for information on the health and economic well-being of adults age 50 and older in the United States. The HRS is a longitudinal project sponsored by the National Institute on Aging and the Social Security Administration. The first cohort was interviewed in 1992. Data on height, weight plus dementia follow-up were available for 9,899 men and women. Participants were linked to mortality registers. Deaths from dementia were defined using ICD 10 G30 (Alzheimer's disease  1971, 1976, 1988, 1999, 2001, 2003, 2005 and 2007 Available ICD codes for dementia as a cause of death varied between study baseline: For NHANES 1971, 1976and 1988, dementia deaths were defined using ICD 9 codes: 209-294, 331.0, 331.1, 331.2, 331.8, 331.9. For NHANES 1999to 2007  Webpage: http://www.cdc.gov/nchs/nhanes/index.htm

WOLF (Work, Lipids, and Fibrinogen) Stockholm and WOLF Norrland studies, Sweden
The WOLF (Work, Lipids, and Fibrinogen) Stockholm study is a prospective cohort study of 5673 people aged 19-70 and with data on BMI from measured height and weight working in companies in Stockholm county. WOLF Norrland is a prospective cohort of 4708 participants with data on BMI aged 19-65 working in companies in Jämtland and Västernorrland counties. At study baseline the participants underwent a clinical examination and completed a set of health questionnaires. For WOLF Stockholm, the baseline assessment was undertaken at 20 occupational health units between November 1992 and June 1995 and for WOLF Norrland at 13 occupational health service units in 1996-98. The Regional Research Ethics Board in Stockholm, and the ethics committee at Karolinska Institutet, Stockholm, Sweden approved the study. Data from Gazel, WOLF-S, WOLF-N, and HeSSup were pooled to achieve sufficient case numbers (labelled IPD-Work other). Dementia was defined using ICD-10, codes F00, F01, F02, F03, G30 and G31 (

Whitehall II, the United Kingdom
The Whitehall II study is a prospective cohort study set up to investigate socioeconomic determinants of health. At study baseline in 1985-1988, 10 308 civil service employees (6 895 men and 3 413 women) aged 35-55 and working in 20 civil service departments in London were invited to participate in the study. Data on BMI from measured height and weight and the outcome measures from phase 3 were available for 8073 men and women who were eligible for our meta-analyses. The Whitehall II study protocol was approved by the University College London Medical School committee on the ethics of human research. Written informed consent was obtained at each data collection wave. Comprehensive tracing of electronic health records for dementia ascertainment was undertaken using three databases: the national hospital episode statistics (HES) database, the Mental Health Services Data Set (MHSDS) and the mortality register. Record linkage until 3Ist of March 2015, using International Classification of Diseases Tenth Edition (ICD-10) codes F00, F01, F02, F03, F05.1, G30, G31.0, G31.1 and G31.8 identified cases of dementia. The National Health Service (NHS) in the UK (England, Scotland, Wales) provides most of the health care, including out-and in-patient care. Private medical insurance, held by around 12% of the UK population (1997 figures),28 is mainly used for elective surgery rather than chronic conditions such as dementia. MHSDS is a national database which contains information for persons in contact with mental health services in hospitals, outpatient clinics, and the community. Mortality data were drawn from the British national mortality register (National Health Services Central Registry). The tracing exercise was carried out using the unique NHS identification number given to each resident in the UK. 10 -20 years >20 years ____________________________________________________________________________________________________________________________ eTable 3. Study-specific estimates for the association of BMI per 5-unit increase with dementia after excluding dementia cases ascertained from death registries in analyses stratified by follow-up period