Susan Jeffrey

July 15, 2014

COPENHAGEN, Denmark — A new study shows that engaging in cognitively stimulating activities, particularly games such as cards or puzzles, is associated with greater brain volumes and higher cognitive test scores in cognitively normal adults at increased risk for Alzheimer's disease (AD).

In a cross-sectional study, participants who reported engaging frequently in game playing had higher brain volumes in regions related to AD, including the hippocampus and posterior cingulate, compared with nonplayers and had higher scores on tests of episodic memory and executive function.

"Taken together, engagement in cognitively stimulating activities might be a useful approach for preserving brain volume and cognitive functions vulnerable to Alzheimer's disease," lead Stephanie Schultz, BSc, from the University of Wisconsin–Madison and the Wisconsin Alzheimer's Disease Research Center, concluded.

While all cognitive activities are useful in this regard, "the game activity showed some unique aspects," Schultz told Medscape Medical News.

The results were reported here at the Alzheimer's Association International Conference (AAIC) 2014.

Brain Games

Previous research has shown that cognitively stimulating activities favorably alter AD-related outcomes, such as amyloid burden, hippocampal atrophy, and cognitive decline, as well as progression to symptomatic AD, Schultz explained. However, these studies have focused mainly on elderly cohorts, and many have used cognitive members of lifelong cognitive activity, she said.

"So the objective of this study was to determine whether midlife engagement in cognitively stimulating activities influences AD-related brain structures and cognitive functions associated with Alzheimer's disease," Schultz said.

Stephanie Schultz

The analysis used data on 329 of approximately 1500 participants in the Wisconsin Registry for Alzheimer's Prevention (WRAP) who had completed the Cognitive Activity Scale (CAS), as well as a comprehensive neuropsychological battery, and structural T1 MRI. The CAS asks whether and how often participants engage in 10 common cognitive activities, such as reading books, attending lectures, and playing games.

"We specifically focused on 1 activity, which was playing games such as cards, checkers, crosswords, and other puzzles, for the thought that this is the activity that best captures the essence of what a cognitively stimulating activity might be," she explained. They also did an exploratory analysis looking at all 10 measures on the CAS as a total composite score.

The tests in the comprehensive neuropsychological battery have previously been shown to map to 6 domains, she said. "We focused on domains associated with episodic memory and executive function, such as speed and flexibility, working memory, immediate memory, and verbal learning and memory."

The mean age of the cohort was 60 years, and participants were at increased risk for AD; for example, 74% had at least 1 parent with AD and 40% were carriers of the apolipoprotein E ε4 risk allele.

"When we looked at the association between game playing and brain volumes, we found that regions such as the hippocampus were significantly larger in those who reported frequent game playing" compared with those regions in infrequent players (P = .028), as was the posterior cingulate (P = .012). "Both the hippocampus and posterior cingulate are really important for memory and thinking and some of the areas earliest affected in the course of Alzheimer's disease," Schultz said.

Similarly, the rostral and caudal anterior cingulate and the rostral and middle frontal regions were also significantly larger among those who reported frequent game playing vs infrequent players. "These regions are measures of executive function which are also very important to look at when you're talking about preclinical Alzheimer's disease," she noted.

Looking at cognitive endpoints, they found that frequent game players had significantly higher scores on domains of verbal learning and memory (P = .005) and immediate memory (P = .021) after adjustment for age and education. "These domains are types of episodic memory, and decrements of episodic memory are a hallmark feature of Alzheimer's disease even in its earliest stages," Schultz said.

In addition, scores for speed and flexibility were also significantly higher for those who frequently played games (P = .008), she added. "Speed and flexibility cover various executive functions, which are necessary for successful engagement in daily life, and are also vulnerable to AD pathology."

They also looked at the CAS total score, but there were no associations with this total composite score and brain volume parameters or cognition, with the exception of immediate memory.

"In summary, frequent game playing was associated with increased brain volume in AD-related regions and higher scores on episodic memory and executive function. The games item was more strongly associated with our outcome measures of brain volume and cognition than the CAS total score, which suggests that maybe game playing serves a unique role in preserving brain and cognitive health," Schultz concluded.

The effects were seen in a middle-aged and asymptomatic cohort, she added, "which is really important to think about when looking at ways to preserve and prevent potentially the onset of Alzheimer's."

While this analysis was a cross-sectional sample that can't address issues of cause and effect, the WRAP cohort is a longitudinal study that began in 2001.

Dr. Ozioma Okonkwo

Senior author on the paper, Ozioma Okonkwo, PhD, also at the University of Wisconsin–Madison, told Medscape Medical News that the group plans next to look at participants' score on the baseline Cognitive Activities Scale questionnaire "and then to look at their cognitive course over time, to see if those who reported engaging in more frequent cognitive activities have a more positive cognitive profile over this past 13 years compared to those who had less frequent engagement in these cognitive activities. That is something that might help begin to shed light on the 'chicken and egg' question."

A Healthier Brain

William Klunk, MD, PhD, distinguished professor of psychiatry and neurology at the University of Pittsburgh School of Medicine, Pennsylvania, and a member of the Alzheimer's Association's Medical and Scientific Advisory Council, moderated a press conference here that featured this new research.

Dr. William Klunk

Asked for his thoughts on these findings, he said, "I think it's interesting that not only did Stephanie show the connection between involvement in a variety of games and cognition, but also apparently a healthier brain, larger volumes."

However, he noted, "the question always is which comes first? Is it the healthy brain that plays games, or is it the brain that plays games that stays healthy? But these are things that can be sorted out. You need these sorts of studies to direct you what to look at."

Further, games are not likely to be played alone, he pointed out. "So there are the social interactions that we know are helpful, and lots of other things that go with that. And this is the challenge — to tease out, is it the games? Is it the social interactions? Is it the fact that you stay healthy enough that you feel like going out and playing games? But it still brings us to focus on a constellation of things that's associated with a better outcome."

The study was funded by the National Institutes of Health and the Association. The authors have disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2014. Abstract IC-O1-03. Presented July 14, 2014.

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