In my experience as director of an Alzheimer’s disease (AD) and memory disorders center, it appears that an increasing number of my cognitively impaired patients are drinking alcohol more regularly. As clinical neurologists, our training in the neurological complications of alcohol use/abuse mainly focus on Wernicke’s encephalopathy, Korsakoff’s Syndrome, peripheral neuropathy, and cerebellar ataxia. Nonetheless, one of the most intriguing aspects of this topic from a neurological perspective is the cognitive impact of chronic mild to moderate continuous alcohol use and binge drinking. This topic has become more important because a significant number of patients over 65 are developing cognitive decline and experts in addiction medicine are beginning to realize that cognitive function is important in management of these individuals. According to various studies, 50 to 80 percent of these individuals present with impaired cognitive function.

The role of alcohol in cognitive decline, especially in the presence of multiple small strokes, Parkinson’s disease, Alzheimer’s disease, and frontal dementia, is difficult to decipher because little information is available on the effect of drinking in these disorders. On the contrary, a good deal of information exists regarding cognitive function and alcohol use by itself. In an article published in Neurology last year, authors concluded that regular and episodic drinking were not consistently associated with cognitive function.1 Worse cognition in participants who stopped drinking during follow-up suggested that inclusion of less healthy ex-drinkers may partly explain poor cognition in non-drinkers. This certainly challenges the notion that mild to moderate drinking is healthy for your heart and brain.

Ahead is a brief survey of literature on the topic.

Alcohol and Cognition

One of the most comprehensive studies on alcohol is a meta-analysis of 143 papers from 250 countries covering 1997-2011. It describes the relationship between moderate drinking of alcohol and aspects of cognition.2 The authors divided the papers into two distinct categories: those that provided ratios of risk between drinkers and non-drinkers (74 papers), and those that did not provide ratios but allowed cognition in drinkers to be rated as “better,” “no difference,” or “worse” than in non-drinkers. They also determined that cognitive testing varied between two different eras: 1977 to 1997, during which neuropsychological testing was used in mostly young to middle-aged adults, and 1998-2011, during which most used the mini mental status exam (MMSE) evaluating mostly older individuals. In studies in which no ratios and standard neuropsychological testing was used in 111,709 subjects younger than 55 years old, heavy drinking of four to six drinks per day was associated with cognitive impairment and higher risk for dementia. Notably, no significant difference in cognition was observed between light to moderate drinkers and non-drinkers.

In studies with ratios of risk in patients older than 55 years of age, 87 percent used MMSE. Eighty percent of these studies took place since 1998 in multiple countries. These studies showed a decreased risk of dementia and cognitive impairment in light to moderate drinkers in older adults by 20 percent, but no significant benefit against rate of cognitive decline.

It is worth noting that this analysis was subject to criticism because some of the studies it used included previous drinkers that quit, which can bias the results. Nineteen of the ratio studies excluded these former drinkers. The meta-analysis showed that most studies did not distinguish the type of alcohol used. Some studies said wine was better, whereas others found no difference between beer or spirits. Of course, another inherent criticism is that male and female drinkers were combined for analysis and it is known the two sexes have different drinking patterns, which may mask a genuine difference among types of alcohol. In this meta-analysis, 23 ratios in the worse cognitively impaired group were carefully reviewed to see why mild to moderate drinking was associated with worse cognitive impairment. After accounting for +APOE4 allele and heavy drinking noted in these cases, the worse group represented only 2.2 percent of the total study. Unfortunately, few studies have looked at +APOE4, drinking, and cognitive decline, therefore more are needed to answer this question.

Another notable aspect about the meta-analysis is that accounting for age, education, sex, and smoking produced no change in the alcohol effects. There was also no difference in outcome between longitudinal or cross sectional studies. Mental status exams were more often associated with finding better cognition in drinkers while neuropsychological tests were more often associated with no difference in cognition between drinkers and non- drinkers. Importantly, the findings suggested that moderate drinking had no impact on dementia in general, AD, or vascular dementia. Other meta-analyses have failed to find a significant benefit of alcohol use against cognitive decline, as well.3

In general, the association of moderate drinking and cognitive risk was found in a majority of the countries studied, however, the authors noted the absence of studies from Eastern Europe and Russia. As for why the MMSE test results were positive in reducing cognitive risk of decline compared to neuropsychological testing group in light to moderate drinkers, the authors pointed out that because many studies used MMSE to increase the validity of the results, while 60 percent of the studies used additional measures of cognition, the judgement of dementia and cognitive impairment were more reliable. The authors also stated that heavy drinking (i.e., greater than three to four drinks a day) is associated with an increased risk of cognitive impairment and dementia in addition to the usual social and society issues in general. Light to moderate drinking of two drinks per day or less in adult men and one drink or less in adult women, does not increase risk of cognitive decline, cognitive impairment, or dementia. These results were echoed by findings from another comprehensive review evaluating the same factors.4

More recently, a study evaluated the relationship of alcohol consumption and cognitive decline in early old age.5 The cohort was the Whitehall II, a British study of civil servants which started in 1985 to 1988 composed of 10,308 participants, 67 percent of which were men men, with an age range of 35 to 55. Participants completed a self-administered questionnaire followed by clinical exams over future years from 1991 to 2009 (four assessments). Mean alcohol consumption was calculated for each participant via questions on frequency and amount of alcohol use and which source of alcohol consumed. Alcoholic drinks were converted to grams and divided by seven to obtain daily consumption in grams/day. Those consuming alcohol but not in the third assessment were classified under “alcohol cessation” in the last 10 years. Those that drank but not in the last few weeks in all assessments were classified as “occasional” drinkers. Investigators used cognitive testing in the middle of the study (ages 44-69) and repeated in 2002-04, and 2007-09 (age range 55-80). Short-term memory and executive function (fluency and inductive reasoning, Math, etc.) were used. At inception, roughly 7,500 out of 10,000 participants participated at least one of three cognitive assessments and constituted the analytic sample. Thirteen percent participated in the first wave of cognitive studies, 22.4 percent in two waves, and 64 percent in all three waves of the cognitive study. Men who consumed 36 grams/day of alcohol experienced faster 10-year decline in all cognitive domains, compared to 1.5 to 5.7 extra years of cognitive decline. This was more evident in men than women. Abstinence from drinking was associated with faster decline in global cognitive score and executive function. The number of abstinence drinkers, however, was small and included more women and non-white individuals, which may have altered the data. Overall, the study showed no difference in cognitive decline among alcohol abstainers/quitters and light and moderate drinkers. Alcohol consumption of 36 grams per day (heavy) or greater was associated with faster cognitive decline in all cognitive domains compared with consumption of 0.1 to 19.9 grams/day (light to moderate). In women, however, compared with those drinking 0.1-19.9 grams/day, ten-year abstainers showed faster decline of global cognitive score and executive function. Of note, the data were not driven by a single type of alcohol.

Looking back at the study that prompted me to investigate this topic, several factors are worth pointing out. The investigators looked at 28,947 men and women aged 45-69 years old.1 The baseline study occurred from 2002-2005 and included subjects from Russia, Poland, and Czech towns. Re-exam was done in 2006-08 (63 percent response rate). The cognitive testing included ten-word recall, verbal fluency, letter cancellation test to measure attention, mental speed, and concentration. They had complete cognitive data in 17,022 at the end of the study in 2008. Women who were non-drinkers had lower cognitive scores than light drinkers. Better cognitive scores in moderate drinkers was attenuated adjusting for social, economic, and lifestyle factors. Quantity and frequency of drinking were not associated with cognitive performance in men.

It’s worth pointing out some problems with this study. First, the analytic sample was restricted to participants with cognitive measures at follow-up. Attrition was higher in participants with lower cognitive scores, non-drinkers, and frequent drinkers at baseline, which could possibly bias the results of the study. Also, self-reported alcohol measures typically underestimate actual consumption. In this study, heavy drinkers had lower participation rates and higher likelihood of cognitive impairment, suggesting that heavy drinking and cognitive function were underestimated. The other concern about this study is that the follow-up period was only three years, which may not have been a long enough time to examine trajectories of cognitive decline.

Binge Drinking. Not specifically addressed in the majority of these studies was binge drinking. This topic was specifically evaluated in a 2005 study in which investigators studied 554 Finnish Twins who provided data on alcohol consumption in questionnaires in 1975 and 1981 and were followed for 25 years.6 Participants were 65 years or older at the time of dementia assessment in 1999-2001. The assessments were done by telephone interviews, which have shown a strong correlation with mental assessment face to face. By the end of the follow-up, 103 participants developed dementia, however, the cause of dementia could not be determined from the telephone interview. The study considered binge drinking as five bottles of beer or one bottle of wine on one occasion at least monthly. This was associated with a relative risk of 3.2 (95% confidence interval= 1.2-8.6) for dementia. Also, blacking out during the heavy drinking periods at least twice during the previous year as reported in 1981 was associated with a with a higher risk for dementia in drinkers. The study found that binge drinking and passing out were risk factors even after controlling for alcohol consumption or after excluding from the analysis that were heavy drinkers. Of note, the follow-up period of 25 years was considered longer than most other studies. Participants in studies such as this frequently misreport their drinking habits for 25 years due to perhaps memory problems. Of note, a large proportion of the study population was composed of abstainers (24 percent). It did not appear that abstainers were less healthy than the other study members.

Interestingly, another study found that light to moderate drinkers with occasional binge drinking had a higher mortality than those light to moderate drinkers with such occasions.7 Additionally, a Russian study in 2001 showed that the risk of death from cardiovascular disease was increased in binge drinkers.8 We also know that recurrent head injuries are not uncommon in heavy and binge drinkers and may well be missed in questionnaires and history taking in any study. These data suggest that binge drinking in midlife is associated with increased risk of dementia.

The Effect of Alcohol Overuse and Abstinence on the Brain

When it comes to the exactly how alcohol use affects the brain, the severity of brain lesions depends on various factors including the extent of alcohol consumption, age, gender, and neuropsychological comorbidities.4 The most susceptible brain structures are the neocortex in the frontal lobes, the limbic system and the cerebellum.9 Gray matter reduction involves the frontal parietal regions while white matter reduction is diffuse.10 This latter study showed a 20 percent reduction of the gray matter of the dorsolateral prefrontal cortex and that the aging brain is more sensitive to the deleterious effects of excessive alcohol consumption.11 While this is not terribly surprising, the key word here is “age.” Regardless of the amount of heavy drinking, greater age leads to greater frontal lobe damage. The limbic system, especially the hippocampus, which is involved in episodic memory, is also impaired. The hypothalamus and mammillary bodies are very susceptible to chronic excessive alcohol use and when accompanied by thiamine deficiency leads to well-known Wernicke’s encephalopathy and Korsakoff’s syndrome we all know about. The cerebellum shows reduction of white matter volume in the vermis and cerebellar hemisphere, and connections between cerebellum and frontal lobe via pons and thalamus are impaired.12,13

On the other hand, abstaining from alcohol can have very positive effects. Studies have shown that in the first month of abstinence, brain volume begins to increase, sulci and ventricles start to decline, and evidence of improved executive function and verbal episodic memory begins.14-15 In another study, investigators 54 alcoholics and 54 matched controls matched for age (48 years) and education (very few women) and performed baseline neuropsychological tests assessing episodic memory and executive function and then again after six months of alcohol abstinence. The results over the six-month interval showed that episodic memory and executive function moderately improved and some returned to normal, whereas relapsers performed lower in executive function. There was no significant difference regarding neuropsychological testing scores at baseline between abstainers and relapsers. More importantly, episodic memory and executive impairment did not appear reliable predictors of treatment outcome over a six-month period. More predictable was that the diminished episodic memory and executive function was more likely in older drinkers and longer periods of alcohol abuse.

Brain plasticity is important. An increase in brain volume characterized by increased white matter and gray matter volumes and a reduction in size of the size of the sulci and ventricles is observed right from the first month of abstinence.16 This correlates with improvement with episodic memory and executive function. It has also been shown that new brain regions can be recruited by recently weaned alcohol dependent patients to compensate for alcohol related brain damage.17,18 Studies have shown that alcohol dependent patients recruit neuronal networks parallel to frontal cerebellar circuits normally used by control subjects to perform executive tasks.19 Although abstinence allows improvement of cognitive function, this is only achieved after a period of two to three months. A meta-analysis showed that despite studies showing early cognitive recovery, a global deficit was still present several months after abstinence and the cognitive profile became near normal only after one year of abstinence. However, some cognitive deficits can still be present after one year, such as impaired visual spatial function, which can be observed to be impaired two years after abstinence related to decreased volume of the right parietal cortex.20

Takeaway Points About Alcohol Use And Cognitive Function

Regardless of the limitations of many studies, it is quite clear that heavy drinking is detrimental to brain function, with effects ranging from impairment of memory (encoding and retrieval), executive function, and global cognition, to an increased risk of dementia. The data suggest that mild to moderate drinking (equal to or less than two drinks/day in men, or equal to or greater than one drink/day in women) does not increase risk for cognitive decline or dementia, but actually appears to reduce future cognitive impairment, likely due to its reduced cardiovascular morbidity (see sidebar on page 59).

It is very clear that heavy drinking beyond three or more drinks per day increases cognitive decline, cognitive impairment and risk of dementia, but when it begins that rate of decline does not correlate with this or other level of drinking. Increased cardiovascular morbidity plays a big role in its negative affect. Binge drinking has been studied less but drinking greater than five beers or one bottle of wine at one time, a minimum of one time a month, has been shown to increase cognitive decline and dementia.

The good news is that abstinence from heavy drinking can lead to improvement in cognitive impairment and in many cases return the patient to normal in three months to one year, depending on length of alcohol abuse and the age of the individual. This is very important to neurologists who see numerous individuals with cognitive impairment on a daily basis. If a detailed alcohol history is taken from the patient—or, perhaps more importantly, the caregiver—and it appears the patient has been drinking heavy or binge drinking, it would make sense to try to encourage the patient to stop drinking and return to the clinic in two to three months sober, if possible. While other neurodegenerative and vascular causes of cognitive impairment do not improve, curbing the overuse of alcohol can in fact result in improvement. n

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