Pauline Anderson

July 21, 2015

WASHINGTON, DC — Researchers are uncovering novel and intriguing risk factors for declining cognition — from high levels of physical inactivity and television viewing among young adults to loneliness in older people.

One new study showed that sustained low physical activity beginning in early adulthood was associated with almost double the likelihood of having worse cognitive function, particularly processing speed and executive function, later in life. The same study showed that sustained high levels of TV viewing are also linked to worse midlife cognitive function.

"We were sort of amazed that we could even see these differences in midlife," said Kristine Yaffe, MD, Northern California Institute of Research and Education, University of California, San Francisco, when presenting the research here during a press briefing at the Alzheimer's Association International Conference (AAIC) 2015.

The results are particularly worrisome considering that only half of US adults meet recommended levels of physical activity, Dr Yaffe added.

"We are in the middle of a couch potato kind of situation in which a lot of people are not getting the amount of exercise they should be getting."

Meanwhile, she said, people are embracing a sedentary lifestyle with increasing amounts of "screen time."

Couch Potatoes

The analysis was part of the CARDIA (Coronary Artery Risk Development in Young Adult) study, which enrolled 3375 participants 18 to 30 years of age who had at least three follow-up visits over 25 years. After this time, participants were assessed by using three cognitive tests: the Digit Symbol Substitution Test (DSST), the Stroop test, and the Rey Auditory Verbal Learning Test (RAVLT).

Researchers assessed physical activity through questionnaires. They defined low physical activity as activity below the bottom quartile of baseline levels (<300 kcal/50-minute session three times per week). About 17% of participants had a long-term pattern of low physical activity.

Results showed that compared with those with moderate to high physical activity, the odds ratio (OR) for participants who sustained low physical activity over time to have poor function on the DSST was 1.82 (95% confidence interval [CI], 1.39 - 2.38), adjusted for age, race, sex, education, smoking, body mass index (BMI), and hypertension.

For the Stroop test, the OR for those with low physical activity was 1.38 (95% CI, 1.05 - 1.82). For the RAVLT, the OR for these participants was 1.01 (95% CI, 0.78 - 1.31).

Four Hours of Television

High television viewing was defined as having greater than 4 hours of television watching daily over that 25-year time frame. About 11% of participants had a long-term pattern of high television viewing.

The study uncovered a pattern with TV viewing similar to that of physical activity: Compared with low or moderate TV viewing, the adjusted ORs for high viewers were 1.34 (95% CI, 1.01 - 1.77) for the DSST, 1.61 (95% CI, 1.20 - 2.14) for Stroop, and 1.20 (95% CI, 0.92 - 1.60) for RAVLT.

The researchers also looked at the combined effect of meeting both low physical activity and high TV viewing criteria at two of three visits over time. They found that adults with both (about 3% of the sample) had the highest risk for poor midlife cognitive function.

"What we found was that this 25-year pattern of low physical activity and high TV watching, or sedentary behavior, was associated with worse cognitive function even in midlife," said Dr Yaffe. "We think this is really important because what's happening in midlife — in your 50s — is setting the stage for what happens over the next 20 or 30 years."

Dr Yaffe and her colleagues are keen to see what happens with these now middle-aged participants in terms of dementia risks over the next few decades.

The study has important public health implications for children and young adults, Dr Yaffe added. "We really need to get them to understand that physical activity and being active is not just important for their weight or for their heart; it's also important for their brain."

Late-Life Loneliness

In a separate study presented here by Nancy Donovan, MD, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, results showed that being lonely — at least in later life — is another risk factor for poor cognitive function.

The study included over 8300 adults aged 65 years and older who participated in the US Health and Retirement Study and were evaluated every 2 years from 1998 to 2010.

To measure loneliness, researchers asked whether participants had felt lonely much of the time during the past week. Those who said "yes" were classified as lonely. In this case, about 18% reported being lonely.

Researchers also assessed depression and classified participants as having no depression (0 depressive symptoms), low depression (1 to 2 symptoms), and high depression (3 to 7 symptoms). Some 20% of the sample "endorsed high depression," said Dr Donovan. Almost half of the lonely participants had high depression.

However, while depression and loneliness may overlap, "you can be lonely without being depressed," noted Dr Donovan. Some lonely study participants had low levels of depression or no depression.

The study found that being lonely was associated with a 20% faster rate of cognitive decline over 10 years, independent of baseline depression, demographic and health factors, and social networks.

Depression was also linked with worse cognition. A high depression category was associated with about a 20% faster rate of cognitive decline. A low level of depression was also associated with about an 8% faster cognitive decline.

"What our findings suggest is that loneliness and low levels of depression have similar physiological effects that operate on a continuous level" and may have a cumulative effect, said Dr Donovan.

It's not clear how loneliness may affect cognition. "The prevailing view is that loneliness may be a sort of psychosocial stress" that can damage the brain by activating stress mechanisms or by increasing inflammatory processes in the brain, she said.

"Increasingly, we are understanding that inflammation may play a role in Alzheimer disease progression."

The study results highlight the importance of addressing loneliness, especially because other evidence links loneliness to greater physical limitations, declines in mobility, and earlier mortality. "At this point, it may be useful to think about treating loneliness in high-risk people, for example those who also have social isolation," said Dr Donovan.

She noted that being both lonely and socially isolated appears to accelerate cognitive decline even more.

Physicians may consider evaluating a patient's social supports and living situation, she added. "It has been shown that living alone is a risk factor for cognitive decline," said Dr Donovan. "It may be that having even one confidante or one significant relationship can make a difference."

Dr Donovan is also looking at loneliness in relation to brain structure and amyloid levels. "I'm interested in whether loneliness is a socio-emotional symptom of cognitive decline — as we start to experience brain changes due to dementia whether our ability to have satisfying relationships becomes impaired."

Asked to comment, Maria Carrillo, PhD, chief science officer, Alzheimer's Association, noted the difficulty in "teasing apart" loneliness from depression. Loneliness could have an independent effect on cognition or it could contribute to depression, which impairs cognition.

"Isolation, loneliness, and even the feeling of loneliness regardless of being in a social setting, is important," said Dr Carrillo. "People should be aware that if their loved ones age in isolation and with a lack of social network, this does not lead to a good outcomes for cognition."

The CARDIA study is supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham, Northwestern University, University of Minnesota, Kaiser Foundation Research Institute, and Johns Hopkins University School of Medicine. CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI. Dr Yaffe is also supported by NIA. Dr Donovan's study received funding from the NIA, Harvard Medical School Dupont-Warren/Livingston Fellowship and the Muriel Silberstein Alzheimer Disease Research Fund. Dr Donovan has disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2015. Oral presentations 02-11-02 and 02-11-06. Presented July 20, 2015.

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