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Association of Low to Moderate Alcohol Drinking With Cognitive Functions From Middle to Older Age Among US Adults

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Importance Studies examining the association of low to moderate drinking with various cognitive functions have yielded mixed findings. Objective To investigate whether associations exist between low to moderate alcohol drinking and cognitive function trajectories or rates of change in cognitive function from middle age to older age among US adults. Design, Setting, and Participants A prospective cohort study of participants drawn from the Health and Retirement Study (HRS), a nationally representative sample of US adults, with mean (SD) follow-up of 9.1 (3.1) years. In total, 19 887 participants who had their cognitive functions measured in the HRS starting in 1996 through 2008 and who had participated in at least 3 biennial surveys were included. The data analysis was conducted from June to November 2019. Exposures Alcohol consumption and aging. Main Outcomes and Measures Trajectories and annual rates of change for the cognitive domains of mental status, word recall, and vocabulary and for the total cognitive score, which was the sum of the mental status and word recall scores. Participants were clustered into 2 cognitive function trajectories for each cognition measure assessed based on their scores at baseline and through at least 3 biennial surveys: a consistently low trajectory (representing low cognitive scores throughout the study period) and a consistently high trajectory (representing high cognitive scores throughout the study period). Results The mean (SD) age of 19 887 participants was 61.8 (10.2) years, and the majority of the HRS participants were women (11 943 [60.1%]) and of white race/ethnicity (16 950 [85.2%]). Low to moderate drinking (<8 drinks per week for women and <15 drinks per week for men) was significantly associated with a consistently high cognitive function trajectory and a lower rate of cognitive decline. Compared with never drinkers, low to moderate drinkers were less likely to have a consistently low trajectory for total cognitive function (odds ratio [OR], 0.66; 95% CI, 0.59-0.74), mental status (OR, 0.71; 95% CI, 0.63-0.81), word recall (OR, 0.74; 95% CI, 0.69-0.80), and vocabulary (OR, 0.64; 95% CI, 0.56-0.74) (all P < .001). In addition, low to moderate drinking was associated with decreased annual rates of total cognitive function decline (β coefficient, 0.04; 95% CI, 0.02-0.07; P = .002), mental status (β coefficient, 0.02; 95% CI, 0.01-0.03; P = .002), word recall (β coefficient, 0.02; 95% CI, 0.01-0.04; P = .01), and vocabulary (β coefficient, 0.01; 95% CI, 0.00-0.03; P = .08). A significant racial/ethnic difference was observed for trajectories of mental status (P = .02 for interaction), in which low to moderate drinking was associated with lower odds of having a consistently low trajectory for white participants (OR, 0.65; 95% CI, 0.56-0.75) but not for black participants (OR, 1.02; 95% CI, 0.74-1.39). Finally, the dosage of alcohol consumed had a U-shaped association with all cognitive function domains for all participants, with an optimal dose of 10 to 14 drinks per week. Conclusions and relevance These findings suggested that low to moderate alcohol drinking was associated with better global cognition scores, and these associations appeared stronger for white participants than for black participants. Studies examining the mechanisms underlying the association between alcohol drinking and cognition in middle-aged or older adults are needed.
Original Investigation | Neurology
Association of Low to Moderate Alcohol Drinking With Cognitive Functions
From Middle to Older Age Among US Adults
Ruiyuan Zhang, MD, MS; Luqi Shen, MS; Toni Miles, MD, PhD; Ye Shen, PhD; Jose Cordero, MD, MPH; Yanling Qi, PhD; Lirong Liang, PhD; Changwei Li, MD, PhD, MPH
Abstract
IMPORTANCE Studies examining the association of low to moderate drinking with various cognitive
functions have yielded mixed findings.
OBJECTIVE To investigate whether associations exist between low to moderate alcohol drinking
and cognitive function trajectories or rates of change in cognitive function from middle age to older
age among US adults.
DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of participants drawn from the
Health and Retirement Study (HRS), a nationally representative sample of US adults, with mean (SD)
follow-up of 9.1 (3.1) years. In total, 19 887 participants who had their cognitive functions measured
in the HRS starting in 1996 through 2008 and who had participated in at least 3 biennial surveys
were included. The data analysis was conducted from June to November 2019.
EXPOSURES Alcohol consumption and aging.
MAIN OUTCOMES AND MEASURES Trajectories and annual rates of change for the cognitive
domains of mental status, word recall, and vocabulary and for the total cognitive score, which was
the sum of the mental status and word recall scores. Participants were clustered into 2 cognitive
function trajectories for each cognition measure assessed based on their scores at baseline and
through at least 3 biennial surveys: a consistently low trajectory (representing low cognitive scores
throughout the study period) and a consistently high trajectory (representing high cognitive scores
throughout the study period).
RESULTS The mean (SD) age of 19887 participants was 61.8 (10.2) years, and the majority of the
HRS participants were women (11 943 [60.1%]) and of white race/ethnicity (16950 [85.2%]). Low to
moderate drinking (<8 drinks per week for women and <15 drinks per week for men) was significantly
associated with a consistently high cognitive function trajectory and a lower rate of cognitive decline.
Compared with never drinkers, low to moderate drinkers were less likely to have a consistently low
trajectory for total cognitive function (odds ratio [OR], 0.66; 95% CI, 0.59-0.74), mental status (OR,
0.71; 95% CI, 0.63-0.81), word recall (OR, 0.74; 95% CI, 0.69-0.80), and vocabulary (OR, 0.64; 95%
CI, 0.56-0.74) (all P< .001). In addition, low to moderate drinking was associated with decreased
annual rates of total cognitive function decline (β coefficient, 0.04; 95% CI, 0.02-0.07; P= .002),
mental status (β coefficient, 0.02; 95% CI, 0.01-0.03; P= .002), word recall (β coefficient, 0.02;
95% CI, 0.01-0.04; P= .01), and vocabulary (β coefficient, 0.01; 95% CI, 0.00-0.03; P= .08). A
significant racial/ethnic difference was observed for trajectories of mental status (P=.02for
interaction), in which low to moderate drinking was associated with lower odds of having a
consistently low trajectory for white participants (OR, 0.65; 95% CI, 0.56-0.75) but not for black
participants (OR, 1.02; 95% CI, 0.74-1.39). Finally, the dosage of alcohol consumed had a U-shaped
(continued)
Key Points
Question Does an association exist
between current low to moderate
alcohol drinking and cognitive function
trajectories or rates of cognitive decline
from middle to older age among
US adults?
Findings In this cohort study of 19 887
participants from the Health and
Retirement Study, with a mean
follow-up of 9.1 years, when compared
with never drinking, low to moderate
drinking was associated with
significantly better trajectories of higher
cognition scores for mental status, word
recall, and vocabulary and with lower
rates of decline in each of these
cognition domains.
Meaning Current low to moderate
alcohol consumption among middle-
aged or older adults may be associated
with better total cognitive function.
+Supplemental content
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Abstract (continued)
association with all cognitive function domains for all participants, with an optimal dose of 10 to 14
drinks per week.
CONCLUSIONS AND RELEVANCE These findings suggested that low to moderate alcohol drinking
was associated with better global cognition scores, and these associations appeared stronger for
white participants than for black participants. Studies examining the mechanisms underlying the
association between alcohol drinking and cognition in middle-aged or older adults are needed.
JAMA Network Open. 2020;3(6):e207922.doi:10.1001/jamanetworkopen.2020.7922
Introduction
Alcohol misuse is a leading cause of morbidity and mortality.
1
Alcohol consumption is associated with
a uniformly increased risk of hypertension and stroke, regardless of dose,
2
and heavy and binge
drinking is associated with a higher risk of cardiovascular disease.
3
However, studies have also found
that low to moderate alcohol consumption is associated with protective effects against
cardiovascular diseases.
4-6
Besides its role in physical health, low to moderate alcohol consumption
has been shown to play a role in the development of cognitive impairment and dementia, conditions
that are highly associated with cardiovascular diseases, although the findings are mixed. Specifically,
some studies have reported benefits to cognitive function associated with low to moderate alcohol
consumption,
7-11
whereas others have found no, minimal, or even adverse effects associated with
alcohol consumption.
12-15
The Nurses’ Health Study
11
followed up with approximately 11 000
participants for 2 years and found that moderate drinkers perform better on general cognitive
function and verbal memory tests and have slower rates of decline with time on these 2 cognitive
functions compared with nondrinkers. Similarly, a 10-year follow-up study among 7153 British civil
servants
16
identified a protective association between low alcohol consumption and rates of global
cognitive function and executive function decline compared with never drinking among women but
not among men. By contrast, the Whitehall II imaging substudy
15
followed up with 550 participants
for more than 30 years and found that even moderate drinking is associated with cognitive
function decline.
Cognitive functions are affected by many factors and vary with time. A single measurement
cannot capture all aspects of cognition function and thus decreases the statistical efficiency of
identifying potential risk factors.
17-19
Using repeated measurements at different follow-up times can
produce a more reliable estimate for both interpopulation and intrapopulation variations of cognitive
functions.
20
Moreover, although cognitive functions may decline with age, this decline is
heterogeneous among people in different age groups.
21,22
Thus, this heterogeneity should also be
considered in studies of cognitive function. A few studies focusing on the association of alcohol
drinking with cognitive function decline have taken repeated measurements into account; however,
those studies used net follow-up time, instead of age, to calculate the rates of cognitive function
decline and did not consider the heterogeneous effects associated with age.
8,9,11,15
The present study investigated the association of low to moderate alcohol consumption with
cognitive functions by using repeated cognition measurements and evaluated the association of low
to moderate alcohol consumption with age-related decline in cognitive function in a nationally
representative sample of middle-aged and older US adults.
JAMA Network Open | Neurology Association of Low to Moderate Alcohol Drinking With Cognitive Functions in US Adults
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Methods
Study Population
The present study was a secondary analysis of data from the Health and Retirement Study (HRS), a
longitudinal panel study that surveys a nationwide representative sample of about 20 000 middle-
aged and older US adults. The HRS participants have been reexamined every 2 years since 1992 (HRS
wave 1) to collect their health and economic information.
23
The HRS initially used the Telephone
Interview for Cognitive Status,
24
a brief telephone screening system to assess cognitive functioning.
Since 1996 (HRS wave 3), a modification of that survey has been used to measure cognitive
functioning.
25
For consistency in measurements of the different waves, the present analyses used
data from wave 3 (1996) and later. Furthermore, we only included participants who participated in at
least 3 biennial surveys. Our study followed the Strengthening the Reporting of Observational
Studies in Epidemiology (STROBE) reporting guideline. This secondary analysis of deidentified data
from the HRS was approved by the institutional review board of the University of Georgia at Athens.
Written informed consent was obtained from all participants in the original HRS. No one received
compensation or was offered any incentive for participating in this study.
Cognitive Function Tests
The HRS used age to determine which cognitive tests would be administered. Specifically, all
respondents older than 65 years received a full set of tests in and before 1998 (wave 4); all new
respondents received a full set of tests regardless of their age after 1998; and all reinterviewed
respondents younger than 65 years received 2 questions self-assessing their memory (present rating
and the changes), immediate and delayed recall tests, a backward counting test, and a serial 7s
subtraction test in which 7 is subtracted from a given number for 5 trials.
25
Because the HRS recruited
additional new participants for each wave of the survey, data collected for each participant’s entry
into the HRS were treated as the baseline for that participant. The follow-up measurements were
defined as measurements of onward waves for each participant.
Cognitive functioning was measured by assessing 3 domains: total word recall, mental status,
and vocabulary. Total word recall was scored as the summed results of an immediate word recall test
and a delayed word recall test and ranged from 0 to 20, reflecting the number of words that a
participant could correctly recall immediately or 5 minutes after they were read a list of 10 words.
Mental status was measured using a set of tests that assess knowledge, language, and orientation,
with scores ranging from 0 to 15. Vocabulary, also known as crystalized intelligence, represents
established knowledge and was tested by assessing the ability of the participants to provide the
definitions of 5 given words, with scores ranging from 0 to 10. The total cognition score was
calculated as the summed scores of the total word recall results and the mental status test results and
ranged from 0 to 35.
25,26
Higher cognition scores indicated better cognitive abilities.
Alcohol Drinking and Covariates
Alcohol consumption was assessed using the following questions: “Have you ever drank any alcoholic
beverages, such as beer, wine, or liquor?”; “In the last 3 months, on average, how many days per week
have you had any alcohol to drink?”; and “In the last 3 months, on the days you drank, about how
many drinks did you have?” After wave 3 of the HRS (1996), participants were initially assessed for
ever drinking.
26
Ever drinkers were further asked for their drinking status in the last 3 months. On the
basis of the answers to those questions at baseline, we categorized HRS participants as never
drinkers, former drinkers, or current drinkers. Former drinkers were defined as participants who
drank alcohol more than 3 months before the baseline interview, and current drinkers were defined
as participants who drank alcohol within 3 months before the interview.
26
For current drinkers, we
calculated the alcohol consumption as the product of the number of days of drinking per week and
the number of drinks per day. Current drinkers were then further categorized as low to moderate
drinkers or heavy drinkers. Women with 8 or more drinks per week or men with 15 or more drinks per
JAMA Network Open | Neurology Association of Low to Moderate Alcohol Drinking With Cognitive Functions in US Adults
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week were categorized as heavy drinkers
27
; otherwise, current drinkers were defined as low to
moderate drinkers. Other covariates included age, sex, race/ethnicity, years of education, marital
status, tobacco smoking status, and body mass index. Tobacco smoking status was categorized into
3 groups: never smoker, former smoker, and current smoker based on self-reported responses to
these 2 questions: “Have you ever smoked cigarettes?” and “Do you smoke cigarettes now?”
Statistical Analysis
Baseline characteristics for all included participants and by cognitive function trajectories are
presented as percentages for categorical variables and mean (SD) values or median values and
interquartile ranges (IQRs) for continuous variables. Nonparametric tests, χ
2
tests, or ttests were
used to compare the distribution of those characteristics by trajectory groups for each cognitive
function measure. Data analyses were performed using data from participants with complete
observations.
Latent variable mixture modeling implemented using the SAS Proc Traj procedure was used to
identify subgroups that shared a similar progression for an outcome over time; more specifically, a
similar trajectory for the various cognitive functions tested during follow-up.
28,29
We fitted all
trajectory models in quadratic form and from a 1-trajectory group up to a 5-trajectory group. The
bayesian information criterion and visual assessment in the balance of the number of participants in
the trajectory groups were used to select the number of groups that best fit the data. Trajectory
analyses were conducted for each cognition domain and for overall cognitive function. When 2
trajectory groups best fit the data, we further assessed the model fit for different forms, with the
optimal model having 2 trajectory groups in cubic form for each cognitive function measure.
The annual rate of age-related change for each individual was calculated by regressing cognitive
function traits with age using all observations that an individual contributed, and the coefficient of
age was treated as the age-related annual rate of change.
Multivariate logistic and linear regressions were used to evaluate associations of alcohol
drinking with cognitive function trajectories and age-related annual rate of change, respectively, after
controlling for age, sex, race/ethnicity, educational level, marital status, smoking status, and body
mass index. The association analyses were also conducted by sex and race/ethnicity. Sex and racial/
ethnic differences were evaluated by adding an interaction term, that is, alcohol drinking by sex or
alcohol drinking by race/ethnicity, respectively, to the fully adjusted model.
We further assessed the potential nonlinear association between the number of drinks per
week and the odds ratio (OR) of being clustered into groups with lower cognitive performance by
using a nonparametric method with restricted cubic splines after controlling for the same set of
covariates as for the regression model.
30
This method used the likelihood ratio method to test the
nonlinearity between the model having only a linear association and the model having a linear
association and cubic spline terms. Sensitivity analyses were performed after excluding participants
with at least 1 chronic disease condition. The analyses were performed from June to November 2019
using SAS, version 9.4 (SAS Institute Inc), and R, version 3.5.1 (The R Foundation). Bonferroni
corrections were applied to account for multiple testing, and a 2-side P= .01, correcting for 4
cognition measures, was considered a statistically significant association.
Results
In total, 19 887 people who participated in the HRS between 1996 and 2008 were included in the
present study study (eFigure 1 in the Supplement), and their mean (SD) follow-up was 9.1 (3.1) years.
Total word recall was measured among all 19 887 HRS participants, mental status and total cognition
score were evaluated among 12 683 (63.8%) participants, and vocabulary was assessed for 9931
(49.9%) participants. As shown in Table 1, the mean (SD) age of all study participants was 61.8 (10.2)
years. The majority of the HRS participants were female (11 943 [60.1%]) and of white race/ethnicity
(16 950 [85.2%]). In total, 10824 (54.4%) participants were ever drinkers, among which, 3767
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(18.9%) were former drinkers and 7057 (35.5%) were current drinkers. Most of the current drinkers
(6010 [85.2%]) were low to moderate drinkers. In addition, among all participants, 7813 (39.5%)
were former smokers, 3704 (18.7%) were current smokers, and 5596 (28.1%) had a marital status of
single or separated. Overall, HRS participants had a mean (SD) of 12.4 (3.1) years of education and
were overweight (mean [SD] body mass index calculated as weight in kilograms divided by height in
meters squared, 27.3 [5.3]).
For each cognitive function measure, participants were categorized into a consistently low
trajectory group (ie, cognitive test scores from baseline through follow-up were consistently low) or
a consistently high trajectory group (ie, cognitive test scores from baseline through follow-up were
consistently high) (Figure 1; eFigure 2 in the Supplement). Of 12 683 participants, 2972 (23.4%) had
a consistently low trajectory for mental status, 9538 of 19 887 (48.0%) for word recall, 2444 of 9931
(24.6%) for vocabulary, and 3619 of 12 683 (28.5%) for total cognitive function score. As shown in
Table 1, for each cognitive function measure, compared with participants in the consistently high
trajectory group, those with a consistently low trajectory were more likely to be older, black
individuals, single or separated, and tobacco smokers, and had fewer years of education and a higher
body mass index. However, individuals with consistently low cognitive function results were less
likely to be a current or former drinker (Table 1; eTable 1 in the Supplement).
The associations of alcohol consumption and cognitive function trajectories are presented in
Table 2. After controlling for all covariates, compared with never drinkers, current low to moderate
drinkers were significantly less likely to be associated with consistently low trajectories for total
cognitive score (OR, 0.66; 95% CI, 0.59-0.74), mental status (OR, 0.71; 95% CI, 0.63-0.81), word
recall 0.74 (95% CI, 0.69-0.80), and vocabulary (OR, 0.64; 95% CI, 0.56-0.74) (all P< .001).
Similarly, among former drinkers, ORs for being in the consistently low trajectory group were 0.72
(95% CI, 0.63-0.82) for the total cognitive score, 0.83 (95% CI, 0.72-0.95) for mental status, 0.76
(95% CI, 0.70-0.83) for word recall, and 0.73 (95% CI, 0.63-0.86) for vocabulary. Heavy drinkers had
lower odds of being in the consistently low trajectory group only for the vocabulary test (OR, 0.51;
95% CI, 0.37-0.71). Low to moderate drinkers were also significantly associated with the age-related
Table 1. Baseline DemographicCharacteristics by Cognitive Function Score
Characteristic
No. (%) of participants
Overall Total cognition score Mental status Word recall Vocabulary
(n = 19 887)
Low
(n = 3619)
High
(n = 9064)
Low
(n = 2972)
High
(n = 9711)
Low
(n = 9538)
High
(n = 10 349)
Low
(n = 2444)
High
(n = 7487)
Age, mean (SD), y 61.8 (10.2) 67.7 (8.4) 67.2 (8.3) 67.9 (8.6) 67.2 (8.2) 61.8 (10.1) 61.8 (10.4) 70.0 (7.7) 69.6 (7.3)
Female 11 943 (60.1) 2055 (56.8) 5389 (59.5) 2035 (68.5) 5409 (55.7) 4930 (51.7) 7013 (67.8) 1455 (59.5) 4484 (59.9)
Black race/ethnicity 2937 (14.8) 1043 (28.8) 637 (7.0) 987 (33.2) 693 (7.1) 2051 (21.5) 886 (8.6) 760 (31.1) 500 (6.7)
Marital status of single
or separated
5596 (28.1) 1429 (39.5) 2601 (28.7) 1297 (43.6) 2733 (28.1) 2857 (30.0) 2739 (26.5) 1034 (42.3) 2342 (31.3)
Educational level,
mean (SD), y
12.4 (3.1) 9.8 (3.6) 12.9 (2.6) 9.5 (3.6) 12.8 (2.7) 11.3 (3.4) 13.4 (2.5) 9.4 (3.4) 12.8 (2.8)
Tobacco smoker
Never 8269 (41.8) 1469 (40.8) 3844 (42.6) 1294 (43.8) 4019 (41.6) 3669 (38.7) 4600 (44.7) 1069 (44.0) 3159 (42.4)
Former 7813 (39.5) 1505 (41.8) 3996 (44.3) 1140 (38.6) 4361 (45.2) 3787 (39.9) 4026 (39.1) 1009 (41.5) 3405 (45.7)
Current 3704 (18.7) 623 (17.3) 1175 (13.0) 520 (17.6) 1278 (13.2) 2035 (21.4) 1669 (16.2) 352 (14.5) 883 (11.9)
Alcohol consumption
Never 9063 (45.6) 2265 (62.6) 3981 (43.9) 1937 (65.2) 4309 (44.4) 4914 (51.5) 4149 (40.1) 1615 (66.1) 3362 (44.9)
Ever 10 824 (54.4) 1354 (37.4) 5083 (56.1) 1035 (34.8) 5402 (55.6) 4624 (48.4) 6200 (59.9) 829 (33.9) 4125 (55.1)
Former 3767 (18.9) 492 (13.6) 1634 (18.0) 416 (14.0) 1710 (17.6) 1606 (16.6) 2161 (20.9) 330 (13.5) 1331 (17.8)
Low to moderate 6010 (30.2) 719 (19.9) 3020 (33.3) 520 (17.5) 3219 (33.1) 2485 (26.1) 3525 (34.0) 436 (17.9) 2426 (32.4)
Heavy 1047 (5.3) 142 (3.9) 430 (4.7) 99 (3.3) 473 (4.9) 526 (5.5) 521 (5.0) 61 (2.5) 370 (4.9)
With a chronic disease 15 346 (77.2) 3161 (87.4) 7405 (81.2) 2610 (87.7) 7956 (82.0) 7619 (80.0) 7727 (74.5) 2138 (87.9) 6325 (84.3)
BMI, mean (SD) 27.3 (5.3) 27.4 (5.2) 26.6 (4.7) 27.5 (5.4) 26.7 (4.6) 27.8 (5.4) 26.9 (5.2) 27.3 (5.1) 26.5 (4.7)
Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).
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annual rate of change, with effect sizes of 0.04 (95% CI, 0.02-0.07; P= .002) for the total cognition
score, 0.02 (95% CI, 0.01-0.03) for mental status, 0.02 (95% CI, 0.01-0.04; P= .01) for word recall,
and 0.01 (95% CI, 0.00-0.03; P= .08) for vocabulary (Figure 2; eFigure 3 in the Supplement).
Spline analyses showed significant U-shaped associations between weekly drinking doses and
the odds of being in the consistently low trajectory group for all cognitive function domains
(eFigure 4 in the Supplement). The weekly drinking dose at the turning points were 12 drinks for the
total cognition score, 13 drinks for mental status, 10 drinks for word recall, and 14 drinks for
vocabulary. Sensitivity analyses among participants with no chronic disease condition showed that
the U-shaped association was still significant for the scores of total word recall (P= .001) and
Figure 1. Trajectories of Cognition Scores FromBaseline Through All Follow-up Assessments
26
22
24
Total cognition score
20
18
16
14
67 69 73 75 7977 81
Age, y
71
Total cognition
A
15
Mental status score
9
10
11
12
13
14
8
69 73 75 7977 81
Age, y
71
Mental status
B
14
12
13
Word recall score
11
10
8
9
7
61 62 63 65 6764 69 7270 71 7473
Age, y
66
Word recall
C
6.5
6.0
Vocabulary score
4.5
3.5
5.0
4.0
3.0
69 7371 75 77 8179
Age, y
Vocabulary
D
Consistently low (n
=
3619)
Consistently low (n
=
9538)
Consistently low (n
=
2972)
Consistently high (n
=
9064)
Consistently high (n
=
10
349)
Consistently high (n
=
9711)
Consistently low (n
=
2444)
Consistently high (n
=
7487)
Shaded areas indicate upper and lower 95% CIs.
Table 2. Association of Alcohol Consumption With Consistently LowTrajectories on Measures of Cognitive Function
a
Alcohol consumption
Total cognitive score Mental status Word recall Vocabulary
OR (95% CI) Pvalue OR (95% CI) Pvalue OR (95% CI) Pvalue OR (95% CI) Pvalue
Never 1 [Reference] 1 [Reference] 1 [Reference] 1 [Reference]
Former 0.72 (0.63-0.82) <.001 0.83 (0.72-0.95) .008 0.76 (0.70-0.83) <.001 0.73 (0.63-0.86) <.001
Low to moderate 0.66 (0.59-0.74) <.001 0.71 (0.63-0.81) <.001 0.74 (0.69-0.80) <.001 0.64 (0.56-0.74) <.001
Heavy 0.87 (0.70-1.10) .24 0.82 (0.64-1.06) .13 1.02 (0.88-1.18) .77 0.51 (0.37-0.71) <.001
Abbreviation: OR, odds ratio.
a
Adjusted for age, sex, race/ethnicity, educational level, marital status, tobacco
smoking, and body mass index.
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vocabulary (P= .004), but not for mental status (P= .88) or total cognition score (P= .19) (eFigure 5
in the Supplement).
The associations of alcohol drinking and cognitive functions were similar between men and
women (eTable 2 in the Supplement) but differed for race/ethnicity. As shown in Table 3,lowto
moderate drinking was significantly associated with lower odds of having a consistently low
trajectory for all 4 cognitive function measures only among white participants. For example, low to
moderate drinking was associated with lower odds of having a consistently low mental status
Figure 2. Association of Alcohol Consumption With the Annual Rate of Change in Cognition Scores
Mental
status
Word
recall
Vocabulary
β Coefficient
0.10
0.08
0.06
0.04
0.02
0
Total cognitive
score
Former drinker
Low to moderate drinker
Heavy drinker
Error bars indicate 95% CIs.
Table 3. Association BetweenAlcohol Drinking Status and Consistently Low Cognitive Function Trajectories
Stratified by Race/Ethnicity
a
Cognitive function
White participants Black participants Pvalue
for interactionNo. OR (95% CI) Pvalue No. OR (95% CI) Pvalue
Total cognitive score
Never drinker 5170 1 [Reference] NA 1075 1 [Reference] NA
Former drinker 1860 0.70
(0.60-0.81)
<.001 266 0.83
(0.60-1.13)
.23 .56
Low to moderate
drinker
3444 0.63
(0.56-0.71)
<.001 295 0.87
(0.63-1.18)
.37 .18
Heavy drinker 528 0.78
(0.61-1.00)
.05 44 2.20
(0.98-4.92)
.06 .02
Mental status
Never drinker 5170 1 [Reference] NA 1075 1 [Reference] NA
Former drinker 1860 0.80
(0.68-0.93)
.004 266 0.86
(0.63-1.17)
.34 .82
Low to moderate
drinker
3444 0.65
(0.56-0.75)
<.001 295 1.02
(0.74-1.39)
.92 .02
Heavy drinker 528 0.76
(0.57-1.00)
.05 44 1.30
(0.64-2.65)
.46 .19
Word recall
Never drinker 7355 1 [Reference] NA 1706 1 [Reference] NA
Former drinker 3246 0.75
(0.68-0.82)
<.001 521 0.85
(0.68-1.07)
.17 .32
Low to moderate
drinker
5402 0.72
(0.66-0.78)
<.001 608 0.89
(0.71-1.12)
.32 .09
Heavy drinker 945 0.98
(0.85-1.15)
.84 102 1.08
(0.64-1.80)
.78 .65
Vocabulary
Never drinker 4143 1 [Reference] NA 833 1 [Reference] NA
Former drinker 1465 0.66
(0.56-0.79)
<.001 196 1.04
(0.73-1.50)
.82 .04
Low to moderate
drinker
2661 0.62
(0.53-0.72)
<.001 201 0.72
(0.49-1.04)
.08 .74
Heavy drinker 401 0.47
(0.33-0.67)
<.001 30 0.79
(0.33-1.87)
.59 .27
Abbreviations: NA, not applicable; OR, odds ratio.
a
Adjusted for age, sex, race, educational level, marital
status, tobacco smoking, and body mass index.
JAMA Network Open | Neurology Association of Low to Moderate Alcohol Drinking With Cognitive Functions in US Adults
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trajectory among white participants (OR, 0.65; 95% CI, 0.56-0.75) but not among black participants
(OR, 1.02; 95% CI, 0.74-1.39) (P= .02 for interaction). In addition, the magnitude of the associations
was stronger among white participants. The Pvalues for the U-shaped associations were lower for
white participants than for black participants and for men compared with women (eFigures 6, 7, 8,
and 9 in the Supplement).
Discussion
The present study found that low to moderate drinking was associated with consistently high
cognitive function trajectories, that is, cognitive test scores at the baseline middle-aged assessment
were relatively high and remained high at each subsequent assessment, and a decreased rate of
cognitive decline with age for middle-aged or older US adults. Alcohol consumption had a U-shaped
relationship with cognitive function scores, with an optimal dosage of 10 to 14 drinks per week for all
participants. The association of low to moderate drinking with higher cognitive function trajectories
was stronger among white participants than among black participants.
Low to moderate alcohol drinking was associated with protecting cognitive function as assessed
by the total cognitive score and the scores of each of the 3 cognition domains tested (mental status,
word recall, and vocabulary). We also found that compared with never drinkers, low to moderate
drinkers had slower rates of cognitive decline across time for all cognition domains evaluated. The
association was strongest for the vocabulary test. These findings are in line with previous research.
The Rancho Bernardo Study in southern California
31
reported that moderate, regular alcohol drinking
was associated with better cognitive function compared with never drinking among community-
dwelling adults with a mean age of 73.2 years. The Nurses’ Health Study
11
results suggested that up
to 1 drink per day was associated with decreased risk of cognitive decline among women aged 70 to
81 years. Our study contributed further evidence that among a nationally representative sample of
middle-aged or older adults, low to moderate drinking was associated with the protection of
cognitive functions that may decrease with age. The association of low to moderate drinking with
cognitive functions varies with age.
15,21,22
The Whitehall II study of 550 participants in the UK
15
reported that moderate drinkers with a mean age of 43 years were more likely to have hippocampal
atrophy, and light drinking did not show a protective association compared with abstinence.
However, that study defined moderate drinking as 14 to 21 units per week, which would be
categorized as heavy drinking in our study. The association of low to moderate drinking with
cognitive function in the younger age group warrants further investigation.
In the present study, although low to moderate drinking was associated with better cognitive
functions and slower rates of cognitive decline, the associations between the weekly drinking dose
and the various cognitive functions were U-shaped. The optimal alcohol dosage associated with
better cognitive function was 10 to 14 drinks per week for all participants. Although the majority of
drinkers in the HRS were low to moderate drinkers, 15.0% of white men (median 6; IQR, 2-12), 4.9%
of white women (median, 3; IQR, 2-7), 15.7% of black men (median, 6; IQR, 2-10), and 5.6% of black
women (median, 4; IQR, 2-6) had more than 14 drinks per week. Public health campaigns are still
needed to further reduce alcohol drinking in middle-aged or older US adults, particularly among men.
The mechanisms underlying the beneficial association of low to moderate alcohol consumption with
cognitive function are unclear. The main hypotheses focus on cerebrovascular and cardiovascular
pathways and on brain-derived neurotrophic factor. Several studies have found that low to moderate
alcohol consumption is associated with better cardiovascular functions, fewer cardiac events, and
longer survival compared with abstainers and heavy drinkers
4-6,32
; thus, the decreased risk of
cognitive impairment has been thought to be associated with alcohol consumption. However, a
recent study found that alcohol consumption increases the risk of hypertension and stroke
regardless of dose,
2
which decreases the likelihood of this potential mechanism. The role of alcohol
drinking in cognitive function may be a balance of its beneficial and harmful effects on the
cardiovascular system. Among low to moderate drinkers, the beneficial effects may outweigh the
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harmful effects on the cardiovascular system. Moderate drinking also increases brain-derived
neurotrophic factor levels, a key regulator of neuronal plasticity and development, in the dorsal
striatum, whereas levels of alcohol consumption leading to intoxication do not alter the mRNA
expression levels of this factor.
33
Strengths and Limitations
Our study has several strengths. First, we analyzed data from a nationally representative, large
sample of middle-aged or older US adults. Thus, findings of our study can be generalized to all
middle-aged or older US adults. Second, repeatedly measured cognitive functions with a mean (SD)
follow-up of 9.1 (3.1) years were used, which allowed us to estimate both long-term trajectories and
age-associated annual rates of change in cognitive functions. Third, we used a group-based trajectory
analysis approach to handle repeated measurements of the cognitive functions, which may eliminate
random variations caused by a single measurement and thus provide higher accuracy of grouping
and estimations.
However, certain limitations should also be acknowledged. First, alcohol consumption was self-
reported, which could introduce recall bias that classifies heavy drinkers as low to moderate drinkers
because participants tend to underestimate their alcohol consumption.
34
Such misclassification
would bias our association estimates toward the null, thus reducing statistical power to detect
associations between alcohol drinking and cognitive functions. However, despite such a bias, our
study still detected significant associations between alcohol consumption and cognitive function;
thus, our data were sufficiently robust. Second, very few HRS participants had high weekly alcohol
consumption, particularly among women and black participants, limiting the power of our analyses
to identify an association of heavy drinking with cognitive function for these groups. Third, alcohol
consumption tended to change with time; thus, this change may be associated with other factors
that led to a change in cognitive function. Our study did not account for this possibility. Fourth, in the
sensitivity analyses among participants with no chronic disease condition at baseline, the U-shaped
associations were significant only for word recall and vocabulary, not for mental status and total
cognitive score. The U-shaped associations for these latter 2 measures in the main analyses might
have been due to confounding by health status. Healthy participants had higher cognitive function
scores and might be engaged in more social activities and have higher alcohol consumption, leading
to the higher cognitive function scores shown in the tails of the U-shaped plots. However, the study
participants were middle-aged or older US adults, and 77.2% of the participants had at least 1 chronic
disease condition. Therefore, the association between alcohol drinking and cognitive function may
be applicable both to healthy people and to those with a chronic disease. Fifth, because fewer
participants had high levels of weekly alcohol drinking, the 95% CIs for the risk of having low
cognitive function among these people were wide. Thus, the reliability of the estimates for this group
could be low.
Conclusions
Our study suggested that low to moderate drinking was associated with better total cognitive
function and better individual cognition domain results for word recall, mental status, and vocabulary
among middle-aged or older men and women in the United States. Low to moderate alcohol use was
also associated with slower rates of cognitive decline in those domains. These associations were
stronger for white participants than for black participants. Furthermore, weekly alcohol consumption
had U-shaped relationships with the cognitive functions assessed, with the strongest associations
with better cognitive functions at a dosage of 10 to 14 drinks per week for all participants.
JAMA Network Open | Neurology Association of Low to Moderate Alcohol Drinking With Cognitive Functions in US Adults
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ARTICLE INFORMATION
Accepted for Publication: March 28, 2020.
Published: June 29, 2020. doi:10.1001/jamanetworkopen.2020.7922
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Zhang R et al.
JAMA Network Open.
Corresponding Author: Changwei Li, MD, PhD, MPH, Department of Epidemiology and Biostatistics, University of
Georgia College of Public Health, B. S. Miller Hall, Room 120, 101 Buck Rd,Athens, GA 30602 (changwei.
li@uga.edu).
Author Affiliations: Department of Epidemiology and Biostatistics, University of Georgia College of Public Health,
Athens (Zhang, L. Shen, Miles, Y.Shen, Cordero, Li); Department of Health Care Administration, College of Health
and Human Services, California State University, Long Beach (Qi); Clinical Epidemiology and Tobacco Dependence
Treatment Research Department, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital
Medical University,Beijing, China (Liang).
Author Contributions: Dr Li had full access to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Concept and design: Miles, Cordero, Qi, Li.
Acquisition, analysis, or interpretation of data: Zhang, L. Shen, Y. Shen, Qi, Liang, Li.
Drafting of the manuscript: Zhang, L. Shen.
Critical revision of the manuscript for important intellectual content: Miles, Y. Shen, Cordero, Qi, Liang, Li.
Statistical analysis: Zhang, L. Shen, Y.Shen, Qi, Li.
Administrative, technical, or material support: L. Shen, Miles, Y. Shen, Liang.
Supervision: Miles, Y. Shen, Cordero, Li.
Conflict of Interest Disclosures: None reported.
Funding/Support: The present study is supported by the National Center for Advancing Translational Sciences of
the National Institutes of Health under Award UL1TR002378.
Role of the Funder/Sponsor:The funder had no role in the design and conduc t of the study; collection,
management, analysis, and interpretation of the data; preparation, review, or approvalof the manuscript; and
decision to submit the manuscript for publication.
Disclaimer: The content of this study is solely the responsibility of the authors and does not necessarily represent
the official views of the National Institutes of Health.
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SUPPLEMENT.
eTable 1. Baseline Statistics of the Study Population With PValues for Between Group Differences
eTable 2. Associations of Drinking Status With Cognition Trajectories in Male and Female HRS Participants
eFigure 1. Flowchart for Participants Selection and Cohort Construction
eFigure 2. Cognition Trajectories (Mean Score) for 4 Cognitive Functions
eFigure 3. Distribution of Annual Changing Rate in Different Drinking Groups
eFigure 4. Nonlinear Relationship Between Weekly Drinking Level and Cognition Trajectory Among Current and
Never Drinkers
eFigure 5. Sensitivity Analyses for Nonlinear Relationship Between Weekly Drinking Leveland Cognition Trajectory
Among Healthy Current and Never Drinkers
eFigure 6. Nonlinear Relationship Between Weekly Drinking Leveland Cognition Trajectory Among Male Current
and Never Drinkers
eFigure 7. Nonlinear Relationship Between Weekly Drinking Level and Cognition Trajectory Among Female Current
and Never Drinkers
eFigure 8. Nonlinear Relationship Between Weekly Drinking Leveland Cognition Trajectory Among White Current
and Never Drinkers
eFigure 9. Nonlinear Relationship Between Weekly Drinking Level and Cognition Trajectory Among African
American (AA) Current and Never Drinkers
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... 44) Findings from a study on the association of low to moderate alcohol drinking on cognitive functions from middle to old age among American adults revealed that <8 drinks per week for women and <15 drinks per week for men were positively associated with a consistently high cognitive function trajectory and a lower rate of cognitive decline, while low to moderate drinking was associated with decreased annual rates of total cognitive function decline, word recall, and vocabulary. 45) ...
... In addition, consumption of >14 units of alcohol per week increases the risk of dementia, suggesting the proactive need for a downward revision of alcohol consumption guidelines globally to promote cognitive health. [39][40][41][42][43][44][45] 6 ...
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... The conflicting results could be because these studies used different tools to evaluate cognitive dysfunction; the definitions of the quantity and pattern of alcohol drinking, smoking status, educational and occupational attainment, comorbidities, and psychotropic drugs use of the drinkers and non-drinkers were different [4,11]. However, the recent studies have indicated that a low or moderate amount of alcohol consumption is associated with a lower risk of cognitive impairment [23]. These findings are consistent with our study result that low to moderate alcohol consumption was associated with a lower risk of (2) alcohol drinking can reduce systemic inflammation and facilitate antioxidant effect [25]; (3) Moderate alcohol drinking was reported to increase the levels of brainderived neurotrophic factor (a key regulator of neuronal plasticity and development) in the dorsal striatum [26]. ...
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Background Dementia indicates a significant disease burden worldwide with increased population aging. This study aimed to investigate the impact of alcohol consumption on the risk of cognitive impairment in older adults. Methods Participants ≥ 60 years were administered the Digit Symbol Substitution Test (DSST) to evaluate cognitive function in National Health and Nutrition Examination Survey (NHANES) cycles from 1999 to 2002 and 2011 to 2014 for enrollment in the present study. Participants were categorized into non-drinker, drinker, and heavy drinker groups. Logistic regression analyses were performed to explore associations between cognitive impairment and alcohol consumption. Results Multivariate analysis showed that older adults, men, people from minority races, persons with lower education or income levels, social difficulties, hypertension, or chronic kidney disease were significantly associated with a higher risk of cognitive impairment (all p < 0.05). In the young old (60–69 years), heavy amount of alcohol drinking was significantly associated with lower risk of cognitive impairment compared with drinkers [adjusted odds ratio (aOR): 0.280, 95% Confidence interval (CI) 0.095–0.826]. But in the middle old persons (≥ 70 years), heavy alcohol drinking was associated with higher risk of cognitive impairment (aOR: 2.929, 95% CI 0.624–13.74). Conclusions Our study demonstrated that light to heavy drinking was associated with lower risk of cognitive impairment in participants aged between 60 and 69 years, but caution is needed in the middle old people with heavy alcohol drinking.
... While evidence supports a deleterious influence of heavy alcohol consumption on cognition [9][10][11][12][13][14], the role of moderate alcohol intake has been debated. Several studies have shown a decrease in risk of cognitive impairment with light to moderate alcohol consumption, reflected by a J-shaped curve describing the relationship [15][16][17][18][19][20][21]. This has been shown both for drinking patterns in middle age [22][23][24] and later life [25][26][27]. ...
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Introduction Much debate exists about the role of light to moderate alcohol intake and subsequent cognitive function. The apolipoprotein E genotype may modify the relationship. Methods Using data from the Honolulu-Asia Aging Study, a longitudinal population-based cohort (n = 2,416), Cox proportional hazards regression analyses were performed to measure midlife alcohol intake (average age = 52 years) and later life cognitive function (average age = 87 years) and to explore the role of apolipoprotein E genotype. Results No protective effect of light drinking (>1 drink/month– 1 drink/day) or moderate drinking (>1–2 drinks/day) was observed in the cohort in adjusted models (HR = 1.013, CI:0.88–1.16; HR = 1.104, CI:0.91–1.34, respectively). Heavy drinking (>2–4 drinks/day) and very heavy drinking (>4 drinks/day) increased the risk for incident moderate cognitive impairment (HR = 1.355, CI:1.09–1.68; HR = 1.462, CI:1.04–2.05, respectively). When examining the relationship by apolipoprotein E ε4 carrier status, a similar dose-response pattern was observed in both groups with higher hazard ratios for those carrying at least one copy of the apolipoprotein E ℇ4 allele. As alcohol level increased, the age at incident moderate cognitive impairment decreased, especially among those with at least one apolipoprotein E ℇ4 allele. Discussion We did not observe a significant protective effect for light to moderate drinking in midlife and subsequent cognitive impairment in this cohort. Heavy drinking increased the risk for moderate cognitive impairment and decreased the age at incidence, as did carrying at least one allele of the apolipoprotein E ℇ4 gene.
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The relationship between body mass index (BMI) and cognitive impairment remains controversial, especially in older people. This study aims to confirm the association of phenotypic and genetic obesity with cognitive impairment and the benefits of adhering to a healthy lifestyle. This prospective study included 10,798 participants (aged ≥ 50 years) with normal cognitive function from the Health and Retirement Study in the United States. Participants were divided into low (lowest quintile), intermediate (quintiles 2–4), and high (highest quintile) groups according to their polygenic risk score (PRS) for BMI. The risk of cognitive impairment was estimated using Cox proportional hazard models. Higher PRS for BMI was associated with an increased risk, whereas phenotypic obesity was related to a decreased risk of cognitive impairment. Never smoking, moderate drinking, and active physical activity were considered favourable and associated with a lower risk of cognitive impairment compared with current smoking, never drinking, and inactive, respectively. A favourable lifestyle was associated with a low risk of cognitive impairment, even in subjects with low BMI and high PRS for BMI. This study suggest that regardless of obesity status, including phenotypic and genetic, adhering to a favourable lifestyle is beneficial to cognitive function.
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There is growing interest in understanding how ethanol use interacts with advancing age to influence the brain and cognition. Animal models are employed to investigate the cellular and molecular mechanisms of brain aging and age-related neurodegenerative diseases that underlie cognitive decline. However, all too often research on problems and diseases of the elderly are conducted in healthy young animals, providing little clinical relevance. The validity of animal models is discussed and confounds due to age-related differences in anxiety, sensory-motor function, and procedural learning are highlighted in order to enhance the successful translation of preclinical results into clinical settings. The mechanism of action of ethanol on brain aging will depend on the dose, acute or chronic treatment, or withdrawal from treatment and the age examined. Due to the fact that humans experience alcohol use throughout life, important questions concern the effects of the dose and duration of ethanol treatment on the trajectory of cognitive function. Central to this research will be questions of the specificity of alcohol effects on cognitive functions and related brain regions that decline with age, as well as the interaction of alcohol with mechanisms or biomarkers of brain aging. Alternatively, moderate alcohol use may provide a source of reserve and resilience against brain aging. Longitudinal studies have the advantage of being sensitive to detecting the effects of treatment on the emergence of cognitive impairment in middle-age and can minimize effects of stress/anxiety associated with the novelty of alcohol exposure and behavioral testing, which disproportionately influence aged animals. Finally, the effect of alcohol on senescent neurophysiology and biomarkers of brain aging are discussed. In particular, the interaction of age and effects of alcohol on inflammation, oxidative stress, N-methyl-D-aspartate receptor function, and the balance of excitatory and inhibitory synaptic transmission are highlighted.
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Objective To determine associations of alcohol use with cognitive aging among middle-aged men. Method 1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003–2007 to 2016–2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1–4 drinks in past 14 days), light (5–14 drinks), moderate (15–28 drinks), and at-risk drinkers (>28 drinks in past 14 days). Linear mixed-effects regressions modeled cognitive trajectories by alcohol group, with time-based models evaluating rate of decline as a function of baseline alcohol use, and age-based models evaluating age-related differences in performance by current alcohol use. Analyses used standardized cognitive domain factor scores and adjusted for sociodemographic and health-related factors. Results Performance decreased over time in all domains. Relative to very light drinkers, former drinkers showed worse verbal fluency performance, by –0.21 SD (95% CI –0.35, –0.07), and at-risk drinkers showed faster working memory decline, by 0.14 SD (95% CI 0.02, –0.20) per decade. There was no evidence of protective associations of light/moderate drinking on rate of decline. In age-based models, light drinkers displayed better memory performance at advanced ages than very light drinkers (+0.14 SD ; 95% CI 0.02, 0.20 per 10-years older age); likely attributable to residual confounding or reverse association. Conclusions Alcohol consumption showed minimal associations with cognitive aging among middle-aged men. Stronger associations of alcohol with cognitive aging may become apparent at older ages, when cognitive abilities decline more rapidly.
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Purpose This study aims to review the presentation of substance use disorders in older adults, how addiction intertwines with neurocognitive disorders and how to approach this vulnerable population. Design/methodology/approach Electronic data searches of PubMed, Medline and the Cochrane Library (years 2000–2021) were performed using the keywords “neurocognitive,” “dementia,” “substance use,” “addiction,” “older adults” and “elderly.” The authors, in consensus, selected pivotal studies and conducted a narrative synthesis of the findings. Findings Research about substance use disorders in older adults is limited, especially in those with superimposed neurocognitive disorders. Having dual diagnoses can make the identification and treatment of either condition challenging. Management should use a holistic multidisciplinary approach that involves medical professionals and caregivers. Originality/value This review highlights some of the intertwining aspects between substance use disorders and neurocognitive disorders in older adults. It provides a comprehensive summary of the available evidence on treatment in this population.
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Background: Moderate alcohol intake has been associated with reduced cardiovascular risk in many studies, in comparison with abstinence or with heavier drinking. Studies in east Asia can help determine whether these associations are causal, since two common genetic variants greatly affect alcohol drinking patterns. We used these two variants to assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men, contrasting the findings in men with those in women (few of whom drink). Methods: The prospective China Kadoorie Biobank enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, recording alcohol use and other characteristics. It followed them for about 10 years (until Jan 1, 2017), monitoring cardiovascular disease (including ischaemic stroke, intracerebral haemorrhage, and myocardial infarction) by linkage with morbidity and mortality registries and electronic hospital records. 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology-ie, Mendelian randomisation), with stratification by study area to control for variation between areas in disease rates and in genotype-predicted intake. Findings: 33% (69 897/210 205) of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% (6245/302 510) of women. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischaemic stroke (n=14 930), intracerebral haemorrhage (n=3496), and acute myocardial infarction (n=2958); men who reported drinking about 100 g of alcohol per week (one to two drinks per day) had lower risks of all three diseases than non-drinkers or heavier drinkers. In contrast, although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week-ie, near zero to about four drinks per day), it did not have any U-shaped associations with risk. For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral haemorrhage (relative risk [RR] per 280 g per week 1·58, 95% CI 1·36-1·84, p<0·0001) than for ischaemic stroke (1·27, 1·13-1·43, p=0·0001). For myocardial infarction, however, genotype-predicted mean alcohol intake was not significantly associated with risk (RR per 280 g per week 0·96, 95% CI 0·78-1·18, p=0·69). Usual alcohol intake in current drinkers and genotype-predicted alcohol intake in all men had similarly strong positive associations with systolic blood pressure (each p<0·0001). Among women, few drank and the studied genotypes did not predict high mean alcohol intake and were not positively associated with blood pressure, stroke, or myocardial infarction. Interpretation: Genetic epidemiology shows that the apparently protective effects of moderate alcohol intake against stroke are largely non-causal. Alcohol consumption uniformly increases blood pressure and stroke risk, and appears in this one study to have little net effect on the risk of myocardial infarction. Funding: Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, National Natural Science Foundation of China, British Heart Foundation, Cancer Research UK, GlaxoSmithKline, Medical Research Council, and Wellcome Trust.
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Background Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies. Findings In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively. Interpretation In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. Funding UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.
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Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function. Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15). Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy). Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were “alcohol dependent” according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data. Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning. Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall. Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.
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Objectives To investigate the association between alcohol consumption and cardiovascular disease at higher resolution by examining the initial lifetime presentation of 12 cardiac, cerebrovascular, abdominal, or peripheral vascular diseases among five categories of consumption. Design Population based cohort study of linked electronic health records covering primary care, hospital admissions, and mortality in 1997-2010 (median follow-up six years). Setting CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records). Participants 1 937 360 adults (51% women), aged ≥30 who were free from cardiovascular disease at baseline. Main outcome measures 12 common symptomatic manifestations of cardiovascular disease, including chronic stable angina, unstable angina, acute myocardial infarction, unheralded coronary heart disease death, heart failure, sudden coronary death/cardiac arrest, transient ischaemic attack, ischaemic stroke, intracerebral and subarachnoid haemorrhage, peripheral arterial disease, and abdominal aortic aneurysm. Results 114 859 individuals received an incident cardiovascular diagnosis during follow-up. Non-drinking was associated with an increased risk of unstable angina (hazard ratio 1.33, 95% confidence interval 1.21 to 1.45), myocardial infarction (1.32, 1.24 to1.41), unheralded coronary death (1.56, 1.38 to 1.76), heart failure (1.24, 1.11 to 1.38), ischaemic stroke (1.12, 1.01 to 1.24), peripheral arterial disease (1.22, 1.13 to 1.32), and abdominal aortic aneurysm (1.32, 1.17 to 1.49) compared with moderate drinking (consumption within contemporaneous UK weekly/daily guidelines of 21/3 and 14/2 units for men and women, respectively). Heavy drinking (exceeding guidelines) conferred an increased risk of presenting with unheralded coronary death (1.21, 1.08 to 1.35), heart failure (1.22, 1.08 to 1.37), cardiac arrest (1.50, 1.26 to 1.77), transient ischaemic attack (1.11, 1.02 to 1.37), ischaemic stroke (1.33, 1.09 to 1.63), intracerebral haemorrhage (1.37, 1.16 to 1.62), and peripheral arterial disease (1.35; 1.23 to 1.48), but a lower risk of myocardial infarction (0.88, 0.79 to 1.00) or stable angina (0.93, 0.86 to 1.00). Conclusions Heterogeneous associations exist between level of alcohol consumption and the initial presentation of cardiovascular diseases. This has implications for counselling patients, public health communication, and clinical research, suggesting a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary. Registration clinicaltrails.gov (NCT01864031).
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Background: Evidence suggests that moderate alcohol consumption may protect against cognitive decline and dementia. However, uncertainty remains over the patterns of drinking that are most beneficial. Objective: To examine associations between amount and frequency of alcohol consumption with multiple domains of cognitive function in a well-characterized cohort of older community-dwelling adults in southern California. Design: Observational, cross-sectional cohort study. Setting: A research visit between 1988-1992 in Rancho Bernardo, California. Participants: 1624 participants of the Rancho Bernardo Study (mean age ± SD = 73.2 ± 9.3 years). Measurements: Participants completed a neuropsychological test battery, self-administered questionnaires on alcohol consumption and lifestyle, and a clinical health evaluation. We classified participants according to average amount of alcohol intake into never, former, moderate, heavy and excessive drinkers, and according to frequency of alcohol intake, into non-drinkers, rare, infrequent, frequent and daily drinkers. We examined the association between alcohol intake and cognitive function, controlling for age, sex, education, exercise, smoking, waist-hip ratio, hypertension and self-assessed health. Results: Amount and frequency of alcohol intake were significantly associated with cognitive function, even after controlling for potentially related health and lifestyle variables. Global and executive function showed positive linear associations with amount and frequency of alcohol intake, whereas visual memory showed an inverted U-shaped association with alcohol intake, with better performance for moderate and infrequent drinkers than for non-drinkers, excessive drinkers or daily drinkers. Conclusions: In several cognitive domains, moderate, regular alcohol intake was associated with better cognitive function relative to not drinking or drinking less frequently. This suggests that beneficial cognitive effects of alcohol intake may be achieved with low levels of drinking that are unlikely to be associated with adverse effects in an aging population.
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The Health and Retirement Study (HRS) is a nationally representative longitudinal survey of more than 37 000 individuals over age 50 in 23 000 households in the USA. The survey, which has been fielded every 2 years since 1992, was established to provide a national resource for data on the changing health and economic circumstances associated with ageing at both individual and population levels. Its multidisciplinary approach is focused on four broad topics—income and wealth; health, cognition and use of healthcare services; work and retirement; and family connections. HRS data are also linked at the individual level to administrative records from Social Security and Medicare, Veteran’s Administration, the National Death Index and employer-provided pension plan information. Since 2006, data collection has expanded to include biomarkers and genetics as well as much greater depth in psychology and social context. This blend of economic, health and psychosocial information provides unprecedented potential to study increasingly complex questions about ageing and retirement. The HRS has been a leading force for rapid release of data while simultaneously protecting the confidentiality of respondents. Three categories of data—public, sensitive and restricted—can be accessed through procedures described on the HRS website (hrsonline.isr.umich.edu).
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Russian adults have extraordinarily high rates of premature death. Retrospective enquiries to the families of about 50 000 deceased Russians had found excess vodka use among those dying from external causes (accident, suicide, violence) and eight particular disease groupings. We now seek prospective evidence of these associations. In three Russian cities (Barnaul, Byisk, and Tomsk), we interviewed 200 000 adults during 1999-2008 (with 12 000 re-interviewed some years later) and followed them until 2010 for cause-specific mortality. In 151 000 with no previous disease and some follow-up at ages 35-74 years, Poisson regression (adjusted for age at risk, amount smoked, education, and city) was used to calculate the relative risks associating vodka consumption with mortality. We have combined these relative risks with age-specific death rates to get 20-year absolute risks. Among 57 361 male smokers with no previous disease, the estimated 20-year risks of death at ages 35-54 years were 16% (95% CI 15-17) for those who reported consuming less than a bottle of vodka per week at baseline, 20% (18-22) for those consuming 1-2·9 bottles per week, and 35% (31-39) for those consuming three or more bottles per week; trend p<0·0001. The corresponding risks of death at ages 55-74 years were 50% (48-52) for those who reported consuming less than a bottle of vodka per week at baseline, 54% (51-57) for those consuming 1-2·9 bottles per week, and 64% (59-69) for those consuming three or more bottles per week; trend p<0·0001. In both age ranges most of the excess mortality in heavier drinkers was from external causes or the eight disease groupings strongly associated with alcohol in the retrospective enquiries. Self-reported drinking fluctuated; of the men who reported drinking three or more bottles of vodka per week who were reinterviewed a few years later, about half (185 of 321) then reported drinking less than one bottle per week. Such fluctuations must have substantially attenuated the apparent hazards of heavy drinking in this study, yet self-reported vodka use at baseline still strongly predicted risk. Among male non-smokers and among females, self-reported heavy drinking was uncommon, but seemed to involve similar absolute excess risks. This large prospective study strongly reinforces other evidence that vodka is a major cause of the high risk of premature death in Russian adults. UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union, WHO International Agency for Research on Cancer.
Article
To examine the association between alcohol consumption in midlife and subsequent cognitive decline. Data are from 5,054 men and 2,099 women from the Whitehall II cohort study with a mean age of 56 years (range 44-69 years) at first cognitive assessment. Alcohol consumption was assessed 3 times in the 10 years preceding the first cognitive assessment (1997-1999). Cognitive tests were repeated in 2002-2004 and 2007-2009. The cognitive test battery included 4 tests assessing memory and executive function; a global cognitive score summarized performances across these tests. Linear mixed models were used to assess the association between alcohol consumption and cognitive decline, expressed as z scores (mean = 0, SD = 1). In men, there were no differences in cognitive decline among alcohol abstainers, quitters, and light or moderate alcohol drinkers (<20 g/d). However, alcohol consumption ≥36 g/d was associated with faster decline in all cognitive domains compared with consumption between 0.1 and 19.9 g/d: mean difference (95% confidence interval) in 10-year decline in the global cognitive score = -0.10 (-0.16, -0.04), executive function = -0.06 (-0.12, 0.00), and memory = -0.16 (-0.26, -0.05). In women, compared with those drinking 0.1 to 9.9 g/d of alcohol, 10-year abstainers showed faster decline in the global cognitive score (-0.21 [-0.37, -0.04]) and executive function (-0.17 [-0.32, -0.01]). Excessive alcohol consumption in men (≥36 g/d) was associated with faster cognitive decline compared with light to moderate alcohol consumption.