Crossword puzzles, serious reading material and stimulating conversation are unlikely to protect most people from Alzheimer's, a study has found.
But keeping the brain active in older age can reduce the risk of dementia in the 20% of individuals who carry a gene linked to the disease, the research suggests.
The findings help explain why past studies looking at the mental benefits of staying mentally and physically active have produced conflicting results.
Researchers in the US looked at 393 dementia-free people over 70 who were divided into different groups according to their education history, the extent to which they kept mentally active, and whether or not they had the APoE4 gene.
Brain scans were carried out to identify biomarkers of Alzheimer's disease, including accumulations of sticky beta-amyloid protein fragments.
Participants with the gene and at least 14 years of education, and who ensured they kept mentally active in middle age, had lower levels of beta-amyloid in their brains than did APoE4 carriers who had not exercised their brains.
But for the study group as a whole, education, occupation and mental and physical activity appeared to have little or no effect on beta-amyloid build up or other dementia biomarkers, the research published in the journal Neurology showed.
Lead scientist Dr Prashanthi Vemuri, from Mayo Clinic, said: "Recent studies have shown conflicting results about the value of physical and mental activity related to the risk of developing Alzheimer's disease, and we noticed that levels of education differed in those studies.
"When we looked specifically at the level of lifetime learning, we found that carriers of the APoE4 gene who had higher education and continued to learn through middle age had fewer amyloid deposition on imaging when compared to those who did not continue with intellectual activity in middle age."
He urged people not to be put off stimulating their brains with activities such as word games, reading, and using computers by the overall findings. There was "substantial evidence" that such activity helped delay age-related memory and thinking problems, he said.
Dr Simon Ridley, head of science at the charity Alzheimer's Research UK, insisted there was increasing evidence that staying mentally active in older age can play a role in staving off dementia.
He added: "In this small study, higher education levels and taking part in mentally challenging activities during mid-life only had an impact on hallmark features of Alzheimer's in a subset of people with a risk gene for the disease.
"As none of the volunteers in the study had symptoms of dementia, it is difficult to make conclusions about the long-term impact of these factors on dementia risk."
Dr Doug Brown, director of research at Alzheimer's Society, said: "Alzheimer's disease is caused by a complex mix of genetics and lifestyle, and it could be that particular groups of people may benefit from making certain lifestyle changes to reduce their risk."