Association of Alcohol-Induced Loss of Consciousness and Overall Alcohol Consumption With Risk for Dementia

Key Points Question Are alcohol-induced loss of consciousness and heavy weekly alcohol consumption associated with increased risk of future dementia? Findings In this multicohort study of 131 415 adults, a 1.2-fold excess risk of dementia was associated with heavy vs moderate alcohol consumption. Those who reported having lost consciousness due to alcohol consumption, regardless of their overall weekly consumption, had a 2-fold increased risk of dementia compared with people who had not lost consciousness and were moderate drinkers. Meaning The findings of this study suggest that alcohol-induced loss of consciousness is a long-term risk factor for dementia among both heavy and moderate drinkers.


Finnish Public Sector study (FPS), Finland
The Finnish Public Sector study is a prospective cohort study comprising the entire public sector personnel of 10 towns (municipalities) and 21 hospitals in the same geographical areas. Participants, who were recruited from employers' records in 2000-2012, were individuals who had been employed in the study organisations for at least six months prior to data collection. In total, 76,626 individuals responded, reported being alcohol consumers and were linked to electronic health records. Ethical approval was obtained from the ethics committee of the Finnish Institute of Occupational Health.
Self-reported height, weight, smoking status, physical activity and alcohol use were collected using questionnaires. The weekly amount of walking, brisk walking, jogging or running was asked and physical inactivity was defined as less than 0.5 hour of each (brisk walking, jogging or running) per week. The weekly amount of both moderate and vigorous activities was calculated for classifying moderate or optimal activity. Alcohol consumption was based on the reported amounts of beer, wine or other mild alcoholic beverages and hard liquors. For each category, seven pre-defined answer alternatives were given and weekly consumption was estimated based on the responses. Binge drinking was assessed by requesting the number of occasions the respondent had passed out due to alcohol consumption during the past 12 months. Responses were categorized as 0 vs 1 or more, the latter referring to binge drinking. In supplementary analyses, binge drinkers were further divided into 3 groups based on the frequency to having passed out: once vs 2-3 times vs >=4 times in past year.
Reference: Kivimäki M, Lawlor DA, Davey Smith G, et al. Socioeconomic position, co-occurrence of behavior-related risk factors, and coronary heart disease: the Finnish Public Sector study. Am J Public Health 2007; 97: 874-9.

Gazel, France
Gazel is a prospective cohort study of 20 625 employees (15 011 men and 5 614 women) of France's national gas and electricity company, Electricité de France-Gaz de France (EDF-GDF). Since the study baseline in 1989, when the participants were aged 35-50 years, they have been posted an annual follow-up questionnaire to collect data on health, lifestyle, individual, familial, social, and occupational factors. Alcohol consumption was measured in 1997 and 9796 reported being alcohol consumers and were included to this study. The GAZEL study received approval from the national commission overseeing ethical data collection in France (Commission Nationale Informatique et Liberté).
Self-reported height, weight and smoking status were collected from questionnaires. Physical activity was enquired with the following response alternatives: Yes, competitively (optimal), regularly at least once a week (intermediate), occasionally (intermediate) or No (inactive). Regarding alcohol consumption, the participant was asked whether or not he consumed wine, beer/cider or aperitifs/digestives during the previous week. For each, the number of days and maximum quantity per day with given response alternatives was asked. Weekly consumption of alcohol was based on the responses.
Self-reported height, weight, smoking status, physical activity and alcohol use were collected using questionnaires. The weekly amount of walking, brisk walking, jogging or running was asked and physical inactivity was defined as less than 0.5 hour of each (brisk walking, jogging or running) per week. The weekly amount of both moderate and vigorous activities was calculated for classifying moderate or optimal activity. Alcohol consumption was based on the reported amounts of beer, wine or other mild alcoholic beverages and hard liquors. For each category, seven pre-defined answer alternatives were given and weekly consumption was estimated based on the responses. Binge drinking was assessed by requesting the number of occasions the respondent had passed out due to alcohol consumption during the past 12 months. Responses were categorized as 0 vs 1 or more, the latter referring to binge drinking. In supplementary analyses, binge drinkers were further divided into 3 groups based on the frequency to having passed out: once vs 2-3 times vs >=4 times in past year.

Still Working
Still Working is an ongoing prospective cohort study. In 1986, the employees (n = 12,173) at all Finnish centres of operation of Enso Gutzeit (a forestry products manufacturer) were invited to participate in a questionnaire survey on demographic, psychosocial and health-related factors. Alcohol consumption was measured at study baseline in 1986 and 8687 provided data, were current alcohol consumers and were linked to dementia follow-up via electronic health records. The study was approved by the ethics committee of the Finnish Institute of Occupational Health.
Self-reported smoking status, physical activity and alcohol consumption were collected from baseline questionnaires. Physical activity was assessed requesting the number of times participated in sport activities per month. Alcohol consumption was assessed by questions on the number of times the respondent used alcohol per week and whether the effect of alcohol use led to any symptoms.
Reference: Kalimo R, Toppinen S. Organizational well-being: ten years of research and development: in a forest industry corporation. In: Kompier M, Cooper C, editors. Preventing Stress, Improving Productivity: European Case Studies in the Workplace. London: Routledge; 1999. p. 52-85.

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 (6895 men and 3413 women) aged 35-55 and working in 20 civil service departments in London were invited to participate in the study. Biological baseline of the study was in 1991-1993 when 6682 participated and were current alcohol consumers. 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.
Participants underwent a clinical examination where their height and weight were measured at the baseline by a clinical staff member. Self-reported smoking status was collected from the questionnaire. Physical activity and alcohol consumption were based on responses from the questionnaire. Weekly hours spent in moderately energetic or vigorous sport activities were requested. Physical inactivity was defined as "no moderate or vigorous exercise". Otherwise the weekly amount of both moderate and vigorous activities was used for classifying moderate or optimal activity. Units of alcohol consumed (spirits, wines, beer) during the last seven days was enquired and weekly consumption was calculated as a sum of the reported amounts.
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), 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.

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 5346 people aged 19-70 and with data on alcohol consumption and were alcohol consumers working in companies in Stockholm county. WOLF Norrland is a prospective cohort of 4313 participants with data on alcohol consumption aged 19-65, working in companies in Jämtland and Västernorrland counties and reported being alcohol consumers. 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 WOLF-S and WOLF-N were pooled to achieve sufficient case numbers.
Participants underwent a clinical examination where their height and weight were measured at the baseline by a clinical staff member. Self-reported smoking status was collected from the questionnaire. Physical activity and alcohol consumption were based on responses from the questionnaire. "No or very little exercise, only occasional walks" was classified as physical inactivity, occasional exercise was classified as moderate and regular exercise as optimal physical activity. The frequency and amount of drinking beer / strong beer / wine / strong wine / spirits was requested and weekly alcohol consumption was derived from the responses.

eAppendix 3. Propensity score matching
To calculate the propensity score, we fitted a logistic regression model for being a passing out drinker including the following characteristics: cohort, sex, age, education, occupational position, physical inactivity, smoking, BMI, hypertension and diabetes. In addition, we included the interaction terms for these characteristics and cohort, sex, age and education.
After estimating the propensity score, we matched each pass-out drinker with two 'no passing out-moderate consumption' drinkers using SAS macro Greedy Matching Technique. Of the controls, 99% were possible to match with at least 0.01 caliber width. The average caliber width was 0.001. eTable 4 shows baseline characteristics for participants who reported passing out and their controls who did not pass out and were moderate drinkers.