Participants were included in the imaging substudy if they were safe to undergo MRI and able to give informed consent. Exclusions were due to incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst), incomplete data on alcohol use (>2 study phases data missing), and missing sociodemographic, health, or cognitive data (fig 2 ⇓ ). 
 
 Cognitive function was assessed longitudinally at phases 3, 5, 7, 9, and 11 and at the time of scanning with lexical (how many words beginning with a specific letter can be generated in one minute) and semantic (how many words in a specific category can be named in one minute) fluency tests. Short term memory recall (20 words) was tested at phases 3, 5, 7, 9, and 11. Cross sectional cognitive performance was measured at the time of the scan with the Montreal cognitive assessment (MoCA, education adjusted), trail making test (TMT-A and B), Rey-Osterrieth complex figure (RCF) test (copy, immediate, delay, recognition), Hopkins verbal learning test (HVLT-R; immediate, delay), Boston naming test (BNT), and digit span and digit substitution test (DSST). Full scale IQ (FSIQ) was estimated at the time of the scan with the test of premorbid functioning-UK version (TOPF-UK), with adjustment for sex and education. 
 
 Age, sex, education, smoking, social activity—such as attendance at clubs and visits with family/friends, physical activity, voluntary work—and component measures of the Framingham stroke risk score—such as blood pressure, smoking, history of cardiovascular events, cardiovascular drugs—were assessed by self report questionnaire. Social class was determined according to occupation at phase 3 (highest class=1, lowest=4). Drugs (number of psychotropic drugs reported as taken) and lifetime history of major depressive disorder (assessed by structured clinical interview for DSM IV) were assessed at the time of the scan. Information about personality traits was determined by questionnaire at phase 1 and included trait impulsivity (question: “Are you hot-headed?”). 
 
 Alcohol variables collected in each phase included units drunk a week, frequency of drinking a week over the previous year, and results of the CAGE screening questionnaire. 28 We used weekly consumption in this analysis as there is less likelihood of a ceiling effect in comparison with drinking frequency. We calculated average alcohol use across the study as mean consumption a week averaged across all study phases. Participants were deemed “abstinent” if they consumed less than 1 unit of alcohol a week. “Light” drinking was defined as between 1 and <7 units a week and “moderate” drinking as 7 to <14 units a week for women and 7 to <21 units for men, based on use in the existing literature and government guidelines (fig 1 ⇓ ). “Unsafe drinking” was defined according to pre-2016 (21 units (168 g) a week for men and 14 units (112 g) for women) and newly revised UK Department of Health guidelines (>14 units (112 g) for men and women) and further categorised (14-20, 21-30, >30 units weekly) for the purposes of the logistic regression analysis. 29 Non-dependent drinkers were defined as those scoring <2 on the CAGE questionnaire. 
 
 Five hundred and fifty people were randomly selected for the current Whitehall II imaging substudy (2012-15) from the Whitehall II cohort study. 27 The Whitehall II study was established in 1985 at University College London, with the aim of investigating the relation between socioeconomic status, stress, and cardiovascular health. It recruited 10 308 non-industrial civil servants across a range of employment grades. Sociodemographic, health, and lifestyle variables (including alcohol use) were measured over a follow-up period of about 30 years, at about five year intervals (phase 1: 1985-88, phase 3: 1991-93, phase 5: 1997-99, phase 7: 2003-04, phase 9: 2007-09, phase 11: 2011-12). To make the sample as representative as possible of the cohort at baseline, we drew a random list of 1380 participants from those who took part in the Whitehall II phase 11 clinical examination or phase 10 pilot examination and had consented. Participants were sampled from high, intermediate, and low socioeconomic groups. 
 
 Diffusion tensor images indicate the directional preference of water diffusion in neural tissue and allow inferences about the structural integrity of white matter tracts. In healthy myelinated fibres diffusion is restricted perpendicular to the longitudinal axis of the fibre—that is, it is anisotropic. We carried out voxel-wise statistical analysis of diffusion tensor data (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)) using tract based spatial statistics (TBSS). 32 
 
 Full technical details are in the appendix. In brief, we initially examined associations between alcohol use and grey matter using voxel based morphometry, an objective method to compare grey matter density between individuals in each voxel (smallest distinguishable image volume) of the structural image. For each participant for subsequent analyses we additionally extracted hippocampal volumes (adjusted for total intracranial volume) using an automated segmentation/registration tool. Automated segmentation of the amygdala was less reliable in this sample so we did not use extracted volumes in this analysis. Three clinicians independently defined hippocampal atrophy according to visual rating (Scheltens score 31 ) and reached a consensus. 
 
 Statistical analysis 
 
 All analyses were done with R,33 unless otherwise stated. To assess representativeness of included participants we examined differences between included and excluded participants using t tests of means (continuous variables) or χ2 tests of independence (categorical variables). According to variable type, we used means (standard deviations), medians (interquartile ranges), or numbers (percentages) to summarise sociodemographic and clinical measures for included participants who were split by safe versus unsafe average alcohol use averaged over all phases, on the basis of UK contemporary (pre-2016) guidelines. Significant differences between safe and unsafe drinkers in continuous variables were tested with t tests of means (normally distributed) or Wilcoxon rank sum tests (non-normally distributed), and in binary categorical variables (and mini-mental state examination, Montreal cognitive assessment, and Framingham stroke risk score, which have lower and upper bounds) with Fisher’s exact test of proportions. In view of small group numbers (<5) for social class, we performed a simulation test to estimate group differences.34 Weekly consumption of alcohol (units and grams) was described with means, standard deviations, medians, and interquartile ranges. 
 
 We examined alcohol trends over time using mixed effects modelling, with time from study baseline (phase 1) as the independent variable and alcohol consumption (units/week) as the dependent variable. This method accounts for missing data and correlation of repeated measures (in this case alcohol use). We calculated intercepts (baseline consumption) and slopes (trends over study) for each participant. The ability of other variables to predict longitudinal trends of alcohol consumption was tested by inclusion of the following in the mixed effects model: age, sex, education, premorbid IQ, social class, Framingham risk score (a composite measure including smoking, cardiovascular disease or diabetes, cardiovascular drugs), exercise frequency, club attendance, voluntary work, visits with friends and family, lifetime history of major depressive disorder on the structured clinical interview for DSM IV (SCID) (yes-2/no-1), and current psychotropic drugs (yes-2/no-1). 
 
 We included mean alcohol consumption (units/week) across all study phases as an independent variable in voxel based morphometry (grey matter density as dependent variable) and tract based spatial statistics analyses (FA/MD/RD/AD as dependent variable). Voxel-wise, we applied a generalised linear model (GLM) using permutation based non-parametric testing (randomise),35 correcting for multiple comparisons across space (threshold-free cluster enhancement, TFCE). 
 
 We used two post hoc tests to confirm the associations between alcohol consumption and hippocampal size after the voxel based morphometry analysis. Firstly, we used logistic regression to calculate odds ratios for left and right hippocampal atrophy versus no atrophy (visual atrophy ratings based on a cut off of 0/1 on the Scheltens scale),31 given average alcohol consumption across study phases. The latter was categorised as abstinent (<1 unit, reference group), 1 to <7 units, 14 to <21 units, 21 to <30 units, and >30 units a week. Secondly, we performed multiple linear regression with hippocampal volume (extracted from FIRST (an automated segmentation/registration tool), adjusted for intracranial volume and transformed by squaring to normalise the residuals) as the dependent variable and alcohol consumption as an independent variable. 
 
 In all analyses with a brain measure as the dependent variable, we included the following potential confounding variables (identified from knowledge of the literature) as independent variables: age, sex, premorbid IQ, education, social class, Framingham risk score, current psychotropic drugs (number), lifetime history of major depressive disorder (structured clinical interview: yes-2/no-1), exercise frequency, club attendance, voluntary work, and visits with friends and family. In the subset with data on personality traits (n=179), analyses were additionally adjusted for impulsiveness. 
 
 We used mixed effects models to model longitudinal cognitive data. For count data (word recall from list of 20: “memory”) we used a binomial regression and for lexical and semantic fluency (performed within a certain time) we used Poisson regression. The following fixed effects were included: time from study baseline, average alcohol consumption across the study (abstinent (reference group, <1 unit weekly), 1- <7, 7- <14, 14- <21, >21), age, sex, education, social class, premorbid IQ, and Framingham stroke risk score. To test whether cognitive decline significantly differed between abstainers and those with higher alcohol intakes, we added interaction terms between time and alcohol category. Contrasts between other categories of drinking were also checked to test for significant differences in cognitive decline—for example, those drinking 1-<7 versus >21 units. We used Wald tests,36 37 estimating the overall effect of all interactions between alcohol and time on the models, to test the null hypothesis that rates of cognitive decline did not differ between alcohol categories. Learning effects have been well demonstrated when the same cognitive test is presented more than once to a participant, which in our study could obscure true cognitive decline. In an attempt to control for this we added a dummy variable to code for the first time the test was taken (First). We also dummy coded for the test being performed at Oxford (Oxford), as there was an atypically short time interval between phase 11 and the last measurement point, which we hypothesised could result in an increased learning effect. We included interaction terms for FSIQ*First and FSIQ*Oxford to check if learning effects differ with premorbid IQ. Participant identification was included as a random effect. Usual diagnostic checks were performed on the models. The resulting coefficients from binomial regression equate to log(odds) and from Poisson regression to log(Poisson mean count). Exponentiated estimates are reported in the appendix. Regression coefficients were converted into interpretable differences in lexical decline per year compared with abstainers by: 100*(1−(exp (estimates)). Models were visually presented with graphs to predict trends in cognitive test scores over the study for a “typical” participant: male, mean age 70, 15 years’ education, social class I, IQ 118, and Framingham stroke risk score 10%. 
 
 We fitted regression models to check whether average alcohol consumption over the study (independent variable) predicted cross sectional performance on a range of memory tests (dependent variable) performed at the study end point. Age, sex, education, and premorbid IQ were included as covariates. When the test score represented a continuous variable, we used multiple linear regression. For count data (such as digit coding), we initially fitted Poisson regression and checked for over-dispersion. If this was found, we used a negative binomial model. For the remainder of the tests, where the upper score is bounded, we initially fitted regression models using binomial distributions. If over-dispersion was in evidence we performed a folded transformation and checked for approximate normality using Q-Q plots of residuals. The same models were re-fitted with and without alcohol consumption, and a hypothesis test (likelihood ratio) was performed. Calculated P values were used to test whether alcohol made a significant difference to the model. 
 
 Structural equation modelling (SEM; Amos 24 for Windows) was used post hoc for hypothesis testing and to generate fit statistics for models of relations between alcohol use, brain measures, and cognitive decline. This modelling allows simultaneous analysis of multiple variables in one model, and time series with auto-correlated errors. The hypothesised underlying structure of the model was constructed following the voxel based morphometry, tract based spatial statistics, and mixed effects analyses, with average alcohol consumption as an exogenous variable, hippocampal volume, corpus callosum mean diffusivity (generally the most sensitive measure of loss of white matter integrity), and decline in lexical fluency (slopes from mixed effects model) included as endogenous variables (with latent variables to account for measurement error). We modelled covariance of alcohol with sex and IQ and between brain measures. The model was improved by iteratively eliminating paths with P>0.1 and monitoring of the successive improvement of the model fits statistics (χ2, comparative fit index, root mean square error of approximation, and the Tucker-Lewis index) until we identified the most parsimonious model. 
 
 In all analyses, results were judged significant if the adjusted P value was <0.05. Bootstrapping was performed to derive 95% confidence intervals for estimates. ||||| CLOSE Scientists have linked moderate or heavy drinking to early symptoms of memory loss. Angeli Kakade (@angelikakade) has the story. Buzz60 
 
 Moderate drinking is associated with worrisome brain changes in a new study. (Photo: Garik_Klimov, Getty Images/iStockphoto) 
 
 Here’s one more reason to think before you drink: even a modest amount of booze might be bad for aging brains. 
 
 A new study published Tuesday in the medical journal BMJ says moderate drinkers were more likely than abstainers or light drinkers to develop worrisome brain changes that might signal eventual memory loss. They also were more likely to show rapid slippage on a language test, though not on several other cognitive tests. 
 
 Moderate drinking in the British study was defined at a level that, in the United States, would equal 8 to 12 small glasses of wine, bottles of beer or shots of liquor each week. 
 
 “Many people drink this way,” and previous studies have suggested they might actually be helping their brains, said lead researcher Anya Topiwala, a clinical lecturer in psychiatry at the University of Oxford. 
 
 The new study casts doubt on that idea, suggesting harm from moderate drinking and no help from light drinking, she said. The study did not look at heavy, abusive drinking, but that already is firmly linked with brain damage and dementia, she noted. 
 
 For the study, she and her colleagues examined three decades of records from 527 British civil servants who are part of a long-running health study. The volunteers, who are predominantly white middle class men, took brief cognitive tests and recorded their drinking histories on multiple occasions, starting at an average age of 43. 
 
 The researchers brought the volunteers in for brain scans, repeated the brief cognitive tests and administered a more extensive battery of memory and thinking tests. 
 
 For the most part, light to moderate drinkers and abstainers performed similarly when they were matched for age, sex, education, social class, physical activity, smoking and other factors. 
 
 There was one exception: moderate to heavy drinkers showed more rapid declines on a language fluency test. The test gives people a minute to name as many words as they can, beginning with a particular letter. 
 
 The brain scans also showed differences. Most notably, the heaviest drinkers were most likely to have clear shrinkage of a part of the brain called the hippocampus, a change that can precede or accompany dementia. Even moderate drinkers were three times more likely than abstainers to show hippocampal shrinkage, the researchers said. 
 
 An important caveat: The study is observational, so it cannot prove cause and effect. It is possible that frequent drinkers had other things in common that accounted for the brain and language changes. 
 
 Still, at this point, “I wouldn’t recommend light to moderate drinking as a strategy to avoid cognitive decline,” Topiwala said. And, she said, it’s not clear how much drinking might be safe from a brain health standpoint. 
 
 U.S. guidelines recommend no more than 1 drink a day for women and 2 drinks a day for men, citing uncertain heart benefits and known risks, including traffic accidents, violence, and a link with breast cancer. Many countries, including the United Kingdom, recommend lower limits for men. 
 
 There is no health reason for anyone who does not drink to take up drinking, said Brian Downer, an assistant professor in the division of rehabilitation sciences at the University of Texas Medical Branch at Galveston. The new research is a good reminder that even moderate drinking can have health consequences, said Downer, who was not involved in the study. 
 
 But, he said, more research on cognitive effects is needed. And none of the findings suggests a need for total abstinence, he said. "You don’t have to feel that you have to completely quit drinking to have a healthy lifestyle.” 
 
 Read or Share this story: https://usat.ly/2sQmSES ||||| Moderate alcohol consumption can impair cognitive function, says study, countering suggestions that low levels of drinking can help protect the brain 
 
 Drinking even moderate amounts of alcohol can damage the brain and impair cognitive function over time, researchers have claimed. 
 
 While heavy drinking has previously been linked to memory problems and dementia, previous studies have suggested low levels of drinking could help protect the brain. But the new study pushes back against the notion of such benefits. 
 
 “We knew that drinking heavily for long periods of time was bad for brain health, but we didn’t know at these levels,” said Anya Topiwala, a clinical lecturer in old age psychiatry at the University of Oxford and co-author of the research. 
 
 Alcohol is a direct cause of seven ​​forms of cancer, finds study Read more 
 
 Writing in the British Medical Journal, researchers from the University of Oxford and University College London, describe how they followed the alcohol intake and cognitive performance of 550 men and women over 30 years from 1985. At the end of the study the team took MRI scans of the participants’ brains. 
 
 None of the participants were deemed to have an alcohol dependence, but levels of drinking varied. After excluding 23 participants due to gaps in data or other issues, the team looked at participants’ alcohol intake as well as their performance on various cognitive tasks, as measured at six points over the 30 year period. 
 
 The team also looked at the structure of the participants’ brains, as shown by the MRI scan, including the structure of the white matter and the state of the hippocampus – a seahorse-shaped area of the brain associated with memory. 
 
 After taking into account a host of other factors including age, sex, social activity and education, the team found that those who reported higher levels of drinking were more often found to have a shrunken hippocampus, with the effect greater for the right side of the brain. 
 
 While 35% of those who didn’t drink were found to have shrinkage on the right side of the hippocampus, the figure was 65% for those who drank on average between 14 and 21 units a week, and 77% for those who drank 30 or more units a week. 
 
 The structure of white matter was also linked to how much individuals drank. “The big fibre tracts in the brain are cabled like electrical wire and the insulation, if you like, on those wires was of a poorer quality in people who were drinking more,” said Topiwala. 
 
 
 
 In addition, those who drank more were found to fare worse on a test of lexical fluency. “[That] is where you ask somebody to name as many words as they can within a minute beginning with a certain letter,” said Topiwala. People who drank between seven and 14 units a week were found to have 14% greater reduction in their performance on the task over 30 years, compared to those who drank just one or fewer units a week. 
 
 By contrast, no effects were found for other tasks such as word recall or those in which participants were asked to come up with words in a particular category, such as ‘animals.’ 
 
 Expert reaction to the the study was mixed. While Elizabeth Coulthard, consultant senior lecturer in dementia neurology at the University of Bristol, described the research as robust, she cautioned that as the study was observational, it does not prove that alcohol was causing the damage to the brain. 
 
 Daily glass of wine increases a woman's cancer risk, finds study Read more 
 
 In addition, the majority of the study’s participants were men, while reports of alcohol consumption are often inaccurate with people underestimating how much they drink – an effect that could have exaggerated the apparent impact of moderate amounts of alcohol. 
 
 Dr Doug Brown, director of research and development at Alzheimer’s Society said that the new research did not imply that individuals should necessarily turn teetotal, instead stressing that it was important to stick to recommended guidelines. 
 
 
 
 In 2016, the Department of Health introduced new alcohol guidelines in the UK, recommending that both men and women drink no more than 14 units of alcohol each week – the equivalent of about six pints of beer or seven 175ml glasses of wine. 
 
 “Although this research gives useful insight into the long-term effects that drinking alcohol may have on the brain, it does not show that moderate alcohol intake causes cognitive decline. However, the findings do contradict a common belief that a glass of red wine or champagne a day can protect against damage to the brain,” said Brown. ||||| (CNN) Drinking in moderation can help our health , some research has showed. Many doctors recommend a glass of wine or beer a night as part of diet plans such as the Mediterranean diet and the DASH diet , which have been proven to keep your heart and brain healthy. However, a new study suggests that even moderate drinking may not be great for your brain. 
 
 As part of the study, which was published Wednesday in the BMJ , researchers looked at people's weekly alcohol intake from the Whitehall II study , which tracks disease and social behaviors in a group of British civil servants for 30 years. University of Oxford and University College London scientists studied how participants fared with regular brain function tests and an MRI. 
 
 What they noted was that the people who drank the most had the highest risk of hippocampal atrophy , a form of brain damage that can impact spatial navigation and can be associated with memory-loss conditions like Alzheimer's and dementia. The heavier drinkers saw a faster decline in language skills and had poorer white matter integrity , which is crucial to processing thoughts quickly. 
 
 If you're starting to worry and are afraid to drown your sorrows, note that there are many caveats, and more research needs to be done. Some experts suggest you shouldn't change your drinking behavior based on this one study, but the results of these brain scans and memory tests for moderate and lighter drinkers were not what researchers expected. 
 
 "We were surprised that the light to moderate drinkers didn't seem to have that protective effect," said study co-author Dr. Anya Topiwala , a clinical lecturer in the Department of Psychiatry at the University of Oxford. "These are people who are drinking at levels that many consider social drinkers, so they are not consuming a lot." 
 
 Even the heaviest of the drinkers aren't big nightly bingers. The "drank the most" group in this study consumed about 30 units of alcohol a week, with a unit considered to be 10 milliliters or 8 grams of pure alcohol. A medium glass of wine has about two units of alcohol, and so does a pint of some beers, depending on the alcohol content. 
 
 If you do the boozy math, the study's heaviest drinkers had a little more than two medium glasses of wine or two beers every night of the week. 
 
 The moderate group was drinking about 14 to 21 units of alcohol per week, or about a medium glass of wine each night, plus a little extra on the weekends. 
 
 Researchers discovered that the moderate group was three times more likely to have hippocampal atrophy compared with people who didn't drink at all. However, in the heavy and moderate drinkers, there is no evidence to show how clinically significant this change is, and there is no evidence linking this loss to any negative general cognitive effects, even the ones for which the participants were tested. 
 
 With the light drinkers, those who had a small glass of wine a night or up to seven units per week, researchers didn't see a significant difference compared with the abstainers, but they didn't see any protective qualities, either. 
 
 The abstainers may be one subject that needs further development, according to Eric Rimm , a professor of medicine and director for the program in cardiovascular epidemiology at Harvard T.H. Chan School of Public Health. 
 
 Rimm, who was not involved in the new study, has researched the impact of alcohol for years. He said that although the study has an interesting hypothesis, the abstainer group (22 men and 15 women) is tiny and may be throwing off the results. 
 
 If you are a moderate drinker, he said, you don't have to give up the booze based solely on this report. 
 
 "There are so many other lifestyle factors that are not taken into account in this study, like nutrition. Eating whole grains and fruits and vegetables have been linked with slower cognitive decline," Rimm said. Attributing mental decline to alcohol is too limited, he said. 
 
 Tom Dening, a professor of dementia research and Director of the Centre for Old Age and Dementia at the University of Nottingham, called the study "most impressive" and suggests it may be a good reminder that "perhaps we should all drink a bit less," but he also questioned its results. People typically are not honest about how much they really drink, he noted. 
 
 "People tend to underestimate their actual consumption, partly to appear more respectable," Dening said. "If actual consumption was under-reported, then the apparent adverse effects of modest amounts of alcohol could have been magnified." 
 
 Earlier studies have also shown that people tend to drink less as they age, said Carl Heneghan , director of the Centre for Evidence-Based Medicine at the University of Oxford, who was not involved in the new research. 
 
 "These type of studies also cannot account for all the (factors), and therefore they cannot, and should not, conclude causation," Heneghan said. "Using all the available evidence provides a much more balanced approach for the public on deciding how much to drink." 
 
 Rimm wondered whether there were so few abstainers in the study because, after 30 years, they hadn't lived as long as the others. 
 
 When it comes to the brain, this is not the first research to question whether drinking even moderate amounts had an impact, though results have been mixed. One 2008 study found that unlike with the heart, for which alcohol has protective qualities, the more people drank, the smaller their total brain volume, meaning their brains aged faster. 
 
 Join the conversation See the latest news and share your comments with CNN Health on Facebook and Twitter. 
 
 "An observational study cannot truly prove that alcohol causes dementia, but the findings are in keeping with my clinical experience," said Dr. Elizabeth Coulthard , a consultant senior lecturer in Dementia Neurology at the University of Bristol who was not involved in the new research. "Hopefully this research will contribute to a greater understanding of true safe limits for alcohol consumption that ensure protection from future dementia. Until we have further studies, the good news is that low alcohol intake was not associated with brain or memory decline in this sample." 
 
 Topiwala said she and her co-authors want to try to replicate the results, particularly with a more diverse population. Most in this study were men with similar backgrounds, with generally higher IQs than the population as a whole, all factors that can affect the results. 
 
 "We think, though, this study asks some really important questions in an area that does have a knowledge gap," Topiwala said.
– A variety of studies have linked heavy drinking to brain damage and dementia, but a new one suggests moderate drinking might also hurt the brain and perhaps lead to memory loss. Contrary to studies suggesting drinking in moderation might actually be good for you, the latest in the British Medical Journal determined that middle-aged moderate drinkers who consumed between eight to 12 shots, bottles of beer, or small glasses of wine per week were more likely than light or non-drinkers to suffer a decline in language ability over a 30-year period, reports USA Today. Perhaps most concerning, moderate drinkers were also three times more likely than non-drinkers to experience a shrinking of the hippocampus, which is responsible for memory. In the study of 527 Brits, mostly middle-class men, researchers found that 35% of non-drinkers had experienced hippocampal atrophy after 30 years, compared to 65% of moderate drinkers and 77% of participants who drank the most, reports the Guardian. As hippocampal atrophy may be linked to dementia, moderate drinking, then, could be tied to future memory loss, reports CNN. Researchers, who expected light to moderate drinkers to be protected from cognitive decline, were "surprised," co-author Anya Topiwala explains. "These are people who are drinking at levels that many consider social drinkers, so they are not consuming a lot." While researchers took age, sex, social activity, and education into account, experts caution that other factors, like diet, may play a role. (Moderate drinking might also increase your breast cancer risk.)