Moderate alcohol consumption and cognitive risk

Figures & data

Figure 1 Cumulative sum histograms (heavy lines) of numbers of studies that did not report various ratios or risk but instead reported “Worse” (heavy solid gray line), “NoDiff” (left, heavy solid black line), or “Better” (right, heavy solid black line) cognition in “social” drinkers (not alcoholics) versus nondrinkers from 1975 to 2011. Thin dotted line at the lower right plots the cumulative sum histogram for studies that reported better cognition and used a MSE to evaluate cognition (b+mse). Thin dashed line plots the cumulative sum histogram for studies of subjects who were ≥55 years of age (gte55). Dashed vertical line at 1998 separates two phases of research on this question (phase I: neuropsychology; phase II: mental status). Inset table shows the breakdown by country of studies reporting worse, no different, or better cognition in drinkers.

Abbreviations: CI, confidence interval; b, better; ge55, ≥55 years of age; HR, hazard ratio; MSE, mental status exam; NoDiff, no different; OR, odds ratio; RR, risk ratio; UK, United Kingdom; USA, United States of America.

Table 1 Cognitive performance in drinkers in “non-ratio” studies, 1977–1986, 1986–1996, and 1997–present

1977–1986 (n = 17)
Worse (8/17 = 47%)	No difference (9/17 = 53%)	Better (0/16 = 0%)
Parker and Noble^Citation35: 102 m	Parker et al^Citation40: 544 f
Parker et al^Citation40: 481 m	Parker et al^Citation43: 21 m, 60 f
Parker et al^Citation44: 45 m	Birnbaum et al^Citation45: 93 f
Jones and Jones^Citation46: 32 f	Cala et al^Citation47: 24 m, 15 f
MacVane et al^Citation48: 106 m	Hannon et al^Citation49: 67 m, 103 f
Hannon et al^Citation50: 40 m	Bergman^Citation51: 192 f
Hannon et al^Citation50: 52 f	Hunt et al^Citation52: 41 m, 39 f
Bergman^Citation51: 195 m	Parsons^Citation53: 100 m
	Jones-Saumty and Zeiner^Citation54: 80 mf
1986–1996 (n = 18)
Worse (4/18 = 22%)	No difference (12/18 = 67%)	Better (2/18 = 11%)
Parker et al^Citation39: 481 m, 544 f	Carey and Maisto^Citation56: 85 f	Farmer et al^Citation57: 834 m, 1198 f
Martin et al^Citation55: 119 m, 134 f	Page and Cleveland^Citation58: 322 m	Nichols et al^Citation59: 22 m
Mangione et al^Citation60: 190 m, 282 f	Bowden^Citation61: 23 m, 17 f
Fox et al^Citation62: 26 m, 5 f	Goodwin et al^Citation63: 124 m, 146 f
	Emmerson et al^Citation64: 80 m
	Alterman and Hall^Citation65: 95 m
	Waugh et al^Citation66: 131 m
	Bates and Tracy^Citation67: 654 m, 654 f
	Salamé^Citation68: 72 m
	Scherr et al^Citation69: 1382 m, 2241 f
	Arbuckle et al^Citation70: 140 m
	Christian et al^Citation71: 4739 m
1997–present (n = 52)
Worse (1/52 = 2%)	No difference (20/52 = 38%)	Better (28/52 = 54%)
Schinka et al^Citation41: 230 mf	Seux et al^Citation18: 751 m	Seux et al^Citation18: 1474 f
	Schinka et al^Citation42: 176 m, 209 f	Cerhan et al^Citation73: 6156 m
	Carmelli et al^Citation72: 566 m	Cerhan et al^Citation73: 7711 f
	Dent et al^Citation74: 209 m	Elias et al^Citation77: 1053 f
	Broe et al^Citation75: 155 m, 162 f	Bond et al^Citation79: 808 m
	Nixon^Citation76: 37 m, 3 f	Bond et al^Citation79: 1028 f
	Elias et al^Citation77: 733 m	Kalmijn et al^Citation80: 989 f
	Sands et al^Citation78: 8080 f	Leroi et al^Citation82: 942 f
	Elwood et al^Citation81: 1649 m	Wang et al^Citation83: 1058 m, 1520 f
	Kalmijn et al^Citation80: 905 m	Bond et al^Citation84: 1856 m
	Leroi et al^Citation82: 546 m	Bond et al^Citation84: 2551 f
	Reid et al^Citation85: 232 m, 569 f	Zimmerman et al^Citation87: 182 f
	Schinka et al^Citation86: 3361 m	Lindeman et al^Citation88: 438 m, 389 f
	Krahn et al^Citation89: 2984 m	Yonker et al^Citation90: 1152 f
	Krahn et al^Citation89: 3453 f	Rodgers et al^Citation91: 3122 m
	Yonker et al^Citation90: 1072 m	Rodgers et al^Citation91: 3281 f
	Richards et al^Citation92: 861 f	Richards et al^Citation92: 903 m
	Stott et al^Citation93: 1804 m	Reid et al^Citation94: 760 m
	Cooper et al^Citation95: 684 m, 1051 f	McDougall et al^Citation96: 60 m
	Andersen et al^Citation97: 1466 m, 1833 f	Ngandu et al^Citation98: 506 m, 835 f
	Caspers et al^Citation99: 118 m	Lang et al^Citation100: 3409 m
	Caspers et al^Citation99: 169 f	Lang et al^Citation100: 3877 f
	Sabia et al^Citation101: 4073 m	Stott et al^Citation93: 3000 f
		Townsend et al^Citation102: 1698 f
		Xu et al^Citation103: 176 m
		Arntzen et al^Citation104: 2227 m
		Arntzen et al^Citation104: 2806 f
		Yamazaki et al^Citation105: 130 m, 110 f

Notes: First section covers 17 studies without ratios from 1977 to 1986, reviewed by Parsons.³⁸ second section covers 18 studies without ratios from 1986 to 1996, reviewed by Parsons and Nixon.³⁷ Third section covers 52 studies without ratios from 1997 to the present. Some studies provide separate results for men (m) and women (f).

Figure 2 (A) Forest plot of all 446 XRs (white dots) plus or minus their 95% CIs (horizontal “whiskers”) from 74 studies providing ratios; ratios are listed in order from smallest to largest. XR_wm is the weighted (wt = 1/SEM²) mean of all 446 ratios from a random-effects meta-analysis model with 95% CI in parentheses. Mean value ±95% CI is to the left of and significantly less than the thick solid vertical line at 1.00 that denotes no difference; this value indicated on the plot’s x axis with ±95% CI (vertical dashed lines). (B) Histogram of the probability density of the log(XR) values with a superimposed smooth probability density curve (solid line) and a superimposed normal distribution density curve (dashed line) calculated using the mean and variance of log(XR). XR_m is the simple (not weighted) antilog of the mean of all log(XR) values with the 95% CI in parentheses; this value indicated on the plot’s x axis with ±95% CI (vertical dashed lines). Small inset graph on left is a normal Q–Q plot showing normality and departures from normality of the log(XR) distribution. Small inset graph on right is funnel plot with P-values for regression (left) and rank correlation (right) tests for asymmetry across top. Note that XR_m is identical to XR_wm.

Abbreviations: CI, confidence interval; HR, hazard ratio; NoQuitters, no quitters; OR, odds ratio; Q–Q, quantile–quantile; RR, risk ratio; SEM, standard error of the mean; wt, weight; XRs, hazard ratios, odds ratios, and risk ratios; XR_wm, weighted mean ratio.

Table 2 The 74 studies providing ratios of risk listed by decade

1980s (n = 4)	1990s (n = 14)	2000s (n = 53)
Heyman et al^Citation106	Hofman and van Duijn^Citation107	Cervilla et al^Citation108
French et al^Citation109	Iliffe et al^Citation110	Commenges et al^Citation111
Amaducci et al^Citation112	Hebert et al^Citation113	Galanis et al^Citation114
Guralnik and Kaplan^Citation115	Ensrud et al^Citation116	Hébert et al^Citation117
	Yoshitake et al^Citation118	Tyas et al^Citation119
	Hendrie et al^Citation120	DeCarli et al^Citation121
	Launer et al^Citation122	Zuccala et al^Citation123
	Dufouil et al^Citation124	Huang et al^Citation125
	Orgogozo et al^Citation126	Lindsay et al^Citation127
	Tsolaki et al^Citation128	Ruitenberg et al^Citation129
	Edelstein et al^Citation130	Tanaka et al^Citation131
	Carmelli et al^Citation132	Truelsen et al^Citation133
	Harwood et al^Citation134	Bachman et al (USA)^Citation135
	Leibovici et al^Citation136	Bachman et al (Nigeria)^Citation135
		Mukamal et al^Citation137
		Zhou et al^Citation138
		Anttila et al^Citation139
		Britton et al^Citation140
		Larrieu et al^Citation141
		Luchsinger et al^Citation142
		Espeland et al^Citation143
		Ganguli et al^Citation144
		Järvenpää et al^Citation145
		Rozzini and Trabucci^Citation146
		Stampfer et al^Citation147
		Dai and Pruett^Citation148
		Deng et al^Citation149
		Ogunniyi et al^Citation151
		Simons et al^Citation152
		Wright et al^Citation153
		Yip et al^Citation154
		McGuire et al^Citation155
		Solfrizzi et al^Citation156
		Vincze et al^Citation157
		Wadley et al^Citation158
		Kivipellto et al^Citation159
		Mehlig et al^Citation160
		Umegaki et al^Citation161
		Barnes et al^Citation162
		Cherbuin et al^Citation163
		Peters et al^Citation164
		Sabia et al^Citation165
		Yaffe et al^Citation166
		Chan et al^Citation167
		Garcia et al^Citation168
		Lobo et al^Citation169
		Lopes et al^Citation170
		Luck et al^Citation171
		Smith et al^Citation172
		Virtaa et al^Citation173
		Yen et al^Citation174
		Au Yeung et al^Citation175
		Gureje et al^Citation150
		Kim et al^Citation176
		Rusanen et al^Citation177
		Weyerer et al^Citation178

Note: Most (about 80%) of the studies took place after 1998 in the mental status era.

Figure 3 (A) Forest plot of 191 XRs (white dots) plus or minus their 95% CIs (horizontal “whiskers”) from 19 studies providing ratios with a reference group that did not include former drinkers. (B) Histogram of the probability density of the log(XR) values with a superimposed smooth probability density curve (solid line) and a superimposed normal distribution density curve (dashed line) calculated using the mean and variance of log(XR).

Notes: The XR_wm in Figure 3A is close to that seen in Figure 2. Other conventions are as for Figure 2.

Abbreviations: CI, confidence interval; HR, hazard ratio; NoQuitters, no quitters; OR, odds ratio; Q–Q, quantile–quantile; RR, risk ratio; SEM, standard error of the mean; XRs, hazard ratios, odds ratios, and risk ratios; XR_wm, weighted mean ratio.

Figure 4 Forest plot of 23 XRs plus or minus their 95% CIs (horizontal “whiskers”) from 18 studies providing ratios where drinkers were significantly worse than nondrinkers.

Abbreviations: ♀, female; ♂, male; 3MS, Modified Mini-Mental State examination; 8t, 8 additional tests; AD, Alzheimer’s disease; ADL, Activities of Daily Living; AMT, Abbreviated Mental Test; CI, confidence interval; D, dementia; DECO, Deterioration Cognitive Observee test; DSST, Digit Symbol Substitution Test; HAMT, Hodkinson Abbreviated Mental Test; HR, hazard ratio; MMSE, Mini-Mental State Examination; MSE, mental status exam; NINCDS/ADRDA, National Institute of Neurological Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association criteria for AD; NoDiff, no different; OR, odds ratio; RR, risk ratio; TELE, telephone screen for cognitive impairment; WDRT, Word Delay Recall Test; XRs, hazard ratios, odds ratios, and risk ratios; XR_wm, weighted mean ratio.

Notes: Uppercase “H” at left of vertical reference line at 1 indicates ratios from heavy drinkers; “e4” indicates presence of apolipoprotein E epsilon 4 allele. Other conventions as in Figure 2A. Note that the XR_wm of 2.43 (95% CI: 1.95–3.03) is much larger than that seen in Figure 2 and is significantly greater than 1.

Figure 5 Overall weighted mean ratios (XR_wm) comparing cognitive function in drinkers and nondrinkers in the various groups analyzed. Group with number of ratios (number of studies) indicated on left; XR_wm (95% confidence interval) given on right.

Note: See text for fuller description.
Abbreviations: AdjAESK, Adjusted for Age, Education, Sex, and Smoking; AlzDem, Alzheimer’s disease; casecon, case-control study; CogDec, cognitive decline; CogImp, cognitive improvement; e4, epsilon 4; heavy, heavy drinkers; light, light drinkers; mod, moderate drinkers; MSE, mental status exam; nodiff, no different; Noe4, no epsilon 4; NoMSE, no mental status exam; Noquitter, no quitters; VascDem, vascular dementia; XR, hazard ratio, odds ratio, and risk ratio; XR_wm, weighted mean ratio; xsect, cross-sectional study.

Figure 6 Overall weighted mean ratios (XR_wm) comparing cognitive risk in drinkers and nondrinkers by country. Country with number of ratios (number of studies) indicated on left; XR_wm (95% confidence interval) given on right.

Abbreviations: afr-amer, African-Americans; australia, Australia; brazil, Brazil; canada, Canada; canada-ne4, Canada, no epsilon 4; chinat, China and Taiwan; chinat-nh, China and Taiwan, no heavy drinkers; denmark, Denmark; denmark-wn, Denmark, wine drinkers; finland, Finland; finl-ne4h, Finland, no epsilon 4, no heavy drinkers; france, France; germany, Germany; greece, Greece; holland, the Netherlands; hungary, Hungary; hungary-nh, Hungary, no heavy drinkers; italy, Italy; japan, Japan; japan-amer, Japanese Americans; japan-nh, Japan, no heavy drinkers; korea, Korea; nigeria, Nigeria; spain, Spain; sweden, Sweden; UK, United Kingdom; USA, United States of America; XR, hazard ratio, odds ratio, and risk ratio.

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