The results showed heavy alcohol consumption over the 30-year period was associated with increased risk of hippocampal atrophy, a form of brain damage that affects memory and spatial navigation.
Volunteers reported periodically on their drinking habits, and scientists carried out brain tests at regular intervals.
At the most recent review, the researchers examined images of the participants' brains - which enabled them to explore correlations between average alcohol use, cognition and brain structure.
Higher consumption was also associated with poorer white matter integrity (critical for efficient cognitive function) and faster decline in language fluency (how many words beginning with a specific letter can be generated in one minute).
Although some studies have argued that light-to-moderate drinking can reduce the risk of dementia and cognitive decline, brain imaging studies have so far come up with contradictory results. They also took standard tests of memory and other mental skills. People typically are not honest about how much they really drink, he noted.
They also question the current limits recommended in the USA which suggest that up to 24.5 units a week is safe for men, as the research suggests increased odds of hippocampal atrophy at just 14-21 units a week. "The toll of high alcohol consumption on cognitive health, often evident to those of us who run memory clinics, is not widely acknowledged publicly", Dr Elizabeth Coulthard, Consultant Senior Lecturer in Dementia Neurology, University of Bristol, commented.
But, even moderate drinkers - classed for the study's purposes as drinking between 11 and 17 standard drinks ( between 14 and 21 United Kingdom units) a week - were three times more likely to have hippocampal atrophy than teetotallers. However even moderate drinkers were not spared they said.
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Although drinking can increase your cancer risk, Rimm points out that many studies have showed that people who consume moderate amounts have much better overall health.
Stockwell, who was not involved in this latest study, has done work examining a popular notion - that drinking, in moderation, is good for the heart.
"I would suggest these findings raise a question mark over the safety of current USA alcohol guidelines, as we found evidence of associations with multiple harmful brain outcomes in individuals drinking within these limits", she said.
"It shows evidence for "hidden" damage to the brain", commented Paul Matthews of Imperial College London, who highlighted the value of the advanced imaging techniques used. "Eating whole grains and fruits and vegetables have been linked with slower cognitive decline", Rimm said.
But few studies have looked at the effects of moderate boozing - 14 to 21 units a week.
"An observational study can not 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.
Topiwala and colleagues analyzed 30 years of records from 527 British civil servants who are participating in a long-term health study.
"Most of the sample in this study were men". "Instead we found the opposite".