Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study

Abstract

Objective: To examine the association between alcohol consumption and risk of dementia.

Design: Prospective cohort study.

Setting: Civil service departments in London (Whitehall II study).

Participants: 9087 participants aged 35-55 years at study inception (1985/88).

Main outcome measures: Incident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017. Measures of alcohol consumption were the mean from three assessments between 1985/88 and 1991/93 (midlife), categorised as abstinence, 1-14 units/week, and >14 units/week; 17 year trajectories of alcohol consumption based on five assessments of alcohol consumption between 1985/88 and 2002/04; CAGE questionnaire for alcohol dependence assessed in 1991/93; and hospital admission for alcohol related chronic diseases between 1991 and 2017.

Results: 397 cases of dementia were recorded over a mean follow-up of 23 years. Abstinence in midlife was associated with a higher risk of dementia (hazard ratio 1.47, 95% confidence interval 1.15 to 1.89) compared with consumption of 1-14 units/week. Among those drinking >14 units/week, a 7 unit increase in alcohol consumption was associated with a 17% (95% confidence interval 4% to 32%) increase in risk of dementia. CAGE score >2 (hazard ratio 2.19, 1.29 to 3.71) and alcohol related hospital admission (4.28, 2.72 to 6.73) were also associated with an increased risk of dementia. Alcohol consumption trajectories from midlife to early old age showed long term abstinence (1.74, 1.31 to 2.30), decrease in consumption (1.55, 1.08 to 2.22), and long term consumption >14 units/week (1.40, 1.02 to 1.93) to be associated with a higher risk of dementia compared with long term consumption of 1-14 units/week. Analysis using multistate models suggested that the excess risk of dementia associated with abstinence in midlife was partly explained by cardiometabolic disease over the follow-up as the hazard ratio of dementia in abstainers without cardiometabolic disease was 1.33 (0.88 to 2.02) compared with 1.47 (1.15 to 1.89) in the entire population.

Conclusion: The risk of dementia was increased in people who abstained from alcohol in midlife or consumed >14 units/week. In several countries, guidelines define thresholds for harmful alcohol consumption much higher than 14 units/week. The present findings encourage the downward revision of such guidelines to promote cognitive health at older ages.

Fig 1

Flow chart of study. Of 10 308 baseline participants, the following were excluded: *1221 (77 died before 1991/93 and 1144 had <2 alcohol measures during 1985/88, 1989/90, and 1991/93 waves); †2339 (77 died before 1991/93 and 2262 did not have data on CAGE or covariates at 1991/93 wave); ‡169 (77 died before 1991/93 and 92 did not have data on covariates during follow-up (missing covariates at a specific wave were replaced by data from closest wave)); §1381 (14 had dementia and 491 died before 2002/04, and 876 had <2 alcohol measures over 1985/88, 1989/90, 1991/93, 1997/99, and 2002/04 waves); ¶1559 (77 died before 1991/93, 1144 had <2 alcohol measures over 1985/88, 1989/90, and 1991/93 waves, and 338 had prevalent cardiometabolic disease)

Fig 2

Association between alcohol consumption per week and risk of dementia by age. *Cox regression analysis adjusted for sociodemographic factors. Dotted lines represent 95% confidence intervals

Fig 3

Multistate models for role of midlife alcohol consumption in transitions to cardiometabolic disease and dementia in all participants.* Analysis based on 8749 participants free of cardiometabolic disease and dementia in 1991/93; 2985 participants had incident cardiometabolic disease (among whom 208 developed dementia); among healthy participants 163 had dementia. Analysis adjusted for age, sex, ethnicity, education, occupational position, and marital status. HR_abstinence=hazard ratio for abstainers versus alcohol consumption of 1-14 units/week; HR_>14u/w=hazard ratio for >14 units/week versus alcohol consumption o=1-14 units/week

Fig 4

Multistate models for role of midlife alcohol consumption in transitions to cardiometabolic disease and dementia in participants with midlife alcohol consumption >14 units/week. Analysis based on 2143 participants free of cardiometabolic disease and dementia in 1991/93; 709 participants had incident cardiometabolic disease (among whom 34 developed dementia); among healthy participants 32 had dementia. Analysis adjusted for age, sex, ethnicity, education, occupational position, and marital status. HR_{7 units/week} associated with a 7 unit increase in alcohol consumption