A new study, involving 1,219 dementia-free older adults (65+), has found that the more omega-3 fatty acids the person consumed, the lower the level of beta-amyloid in the blood (a proxy for brain levels). Consuming a gram of omega-3 more than the average per day was associated with 20-30% lower beta-amyloid levels. A gram of omega-3 equates to around half a fillet of salmon per week.

Participants provided information about their diet for an average of 1.2 years before their blood was tested for beta-amyloid. Other nutrients investigated —saturated fatty acids, omega-6 polyunsaturated fatty acids, mono-unsaturated fatty acid, vitamin E, vitamin C, beta-carotene, vitamin B12, folate and vitamin D — were not associated with beta-amyloid levels.

The results remained after adjusting for age, education, gender, ethnicity, amount of calories consumed and APOE gene status.

The findings are consistent with previous research associating higher levels of omega-3 and/or fish intake with lower risk of Alzheimer’s. Additionally, another recent study provides evidence that the brains of those with Alzheimer’s disease, MCI, and the cognitively normal, all have significantly different levels of omega-3 and omega-6 fatty acids. That study concluded that the differences were due to both consumption and metabolic differences.

More findings from the long-running Mayo Clinic Study of Aging reveal that using a computer plus taking moderate exercise reduces your risk of mild cognitive impairment significantly more than you would expect from simply adding together these two beneficial activities.

The study involved 926 older adults (70-93), of whom 109 (12%) were diagnosed with MCI. Participants completed questionnaires on physical exercise and mental stimulation within the previous year. Computer use was targeted in this analysis because of its popularity as a cognitive activity, and because it was particularly associated with reduced odds of having MCI.

Among the cognitively healthy, only 20.1% neither exercised moderately nor used a computer, compared to 37.6% of those with MCI. On the other hand, 36% of the cognitively healthy both exercised and used a computer, compared to only 18.3% of those with MCI. There was little difference between the two groups as regards exercise but no computer use, or computer use but no exercise.

The analysis took into account calorie intake, as well as education, depression, and other health factors. Daily calorie intake was significantly higher in those with MCI compared to those without (respective group medians of 2100 calories vs 1802) — note that the median BMI was the same for the two groups.

Moderate physical exercise was defined as brisk walking, hiking, aerobics, strength training, golfing without a golf cart, swimming, doubles tennis, yoga, martial arts, using exercise machines and weightlifting. Light exercise included activities such as bowling, leisurely walking, stretching, slow dancing, and golfing with a cart. Mentally stimulating activities included reading, crafts, computer use, playing games, playing music, group and social and artistic activities and watching less television.

It should be noted that the assessment of computer activities was very basic. The researchers suggest that in future studies, both duration and frequency should be assessed. I would add type of activity, although that would be a little more difficult to assess.

Overall, the findings add yet more weight to the evidence for the value of physical exercise and mental stimulation in staving off cognitive impairment in old age, and add the twist that doing both is much better than doing either one alone.

I’ve mentioned before that, for some few people, exercise doesn’t seem to have a benefit, and the benefits of exercise for fighting age-related cognitive decline may not apply to those carrying the Alzheimer’s gene.

New research suggests there is another gene variant that may impact on exercise’s effects. The new study follows on from earlier research that found that physical exercise during adolescence had more durable effects on object memory and BDNF levels than exercise during adulthood. In this study, 54 healthy but sedentary young adults (aged 18-36) were given an object recognition test before participating in either (a) a 4-week exercise program, with exercise on the final test day, (b) a 4-week exercise program, without exercise on the final test day, (c) a single bout of exercise on the final test day, or (d) remaining sedentary between test days.

Exercise both improved object recognition memory and reduced perceived stress — but only in one group: those who exercised for 4 weeks including the final day of testing. In other words, both regular exercise and recent exercise was needed to produce a memory benefit.

But there is one more factor — and this is where it gets really interesting — the benefit in this group didn’t happen for every member of the group. Only those carrying a specific genotype benefited from regular and recent exercise. This genotype has to do with the brain protein BDNF, which is involved in neurogenesis and synaptic plasticity, and which is increased by exercise. The BDNF gene comes in two flavors: Val and Met. Previous research has linked the less common Met variant to poorer memory and greater age-related cognitive decline.

In other words, it seems that the Met allele affects how much BDNF is released as a result of exercise, and this in turn affects cognitive benefits.

The object recognition test involved participants seeing a series of 50 images (previously selected as being highly recognizable and nameable), followed by a 15 minute filler task, before seeing 100 images (the previous 50 and 50 new images) and indicating which had been seen previously. The filler task involved surveys for state anxiety, perceived stress, and mood. On the first (pre-program) visit, a survey for trait anxiety was also completed.

Of the 54 participants, 31 carried two copies of the Val allele, and 23 had at least one Met allele (19 Val/Met; 4 Met/Met). The population frequency for carrying at least one Met allele is 50% for Asians, 30% in Caucasians, and 4% in African-Americans.

Although exercise decreased stress and increased positive mood, the cognitive benefits of exercise were not associated with mood or anxiety. Neither was genotype associated with mood or anxiety. However, some studies have found an association between depression and the Met variant, and this study is of course quite small.

A final note: this study is part of research looking at the benefits of exercise for children with ADHD. The findings suggest that genotyping would enable us to predict whether an individual — a child with ADHD or an older adult at risk of cognitive decline or impairment — would benefit from this treatment strategy.

Interpreting brain activity is a very tricky business. Even the most basic difference can be interpreted in two ways — i.e., what does it mean if a region is more active in one group of people compared to another? A new study not only indicates a new therapeutic approach to amnestic mild cognitive impairment, but also demonstrates the folly of assuming that greater activity is good.

Higher activity in the dentate gyrus/CA3 region of the hippocampus is often seen in disorders associated with an increased Alzheimer's risk, such as aMCI. It’s been thought, reasonably enough, that this might reflect compensatory activity, as the brain recruits extra resources in the face of memory loss. But rodent studies have suggested an alternative interpretation: that the increased activity might itself be part of the problem.

Following on from animal studies, this new study has investigated the effects of a drug that reduces hippocampal hyperactivity. The drug, levetiracetam, is used to treat epilepsy. The 17 patients with aMCI (average age 73) were given a placebo in the first two-week treatment phase and a low dose of the epilepsy drug during the second treatment phase, while 17 controls (average age 69) were given a placebo in both treatment phases. The treatments were separated by four weeks, and brain scans were given at the end of each phase. Participants carried out a cognitive task designed to assess memory errors attributable to a dysfunction in the dentate gyrus/CA3 region (note that these neighboring areas are not clearly demarcated from each other, and so are best analyzed as one).

As predicted, those with aMCI showed greater activity in this region, and treatment with the drug significantly reduced that activity. The drug treatment also significantly improved their performance on the three-choice recognition task, with a significant decrease in memory errors. It did not have a significant effect on general cognition or memory (as measured by delayed recall on the Verbal Paired Associates subtest of the Wechsler Memory Scale, the Benton Visual Retention Test, and the Buschke Selective Reminding Test).

These findings make it clear that the excess activity in the hippocampus is not compensatory, and also point to the therapeutic value of targeting this hyperactivity for those with aMCI. It also raises the possibility that other conditions might benefit from this approach. For example, those who carry the Alzheimer’s gene, APOE4, also show increased hippocampal activity.

Older adults who sleep poorly react to stress with increased inflammation

A study involving 83 older adults (average age 61) has found that poor sleepers reacted to a stressful situation with a significantly greater inflammatory response than good sleepers. High levels of inflammation increase the risk of several disorders, including cardiovascular disease and diabetes, and have been implicated in Alzheimer’s.

Each participant completed a self-report of sleep quality, perceived stress, loneliness and medication use. Around 27% were categorized as poor sleepers. Participants were given a series of tests of verbal and working memory designed to increase stress, with blood being taken before and after testing, as well as three more times over the next hour. The blood was tested for levels of a protein marker for inflammation (interleukin-6).

Poor sleepers reported more depressive symptoms, more loneliness and more perceived stress compared to good sleepers. Before cognitive testing, levels of IL-6 were the same for poor and good sleepers. However, while both groups showed increases in IL-6 after testing, poor sleepers showed a significantly larger increase — as much as four times larger and at a level found to increase risk for illness and death in older adults.

After accounting for loneliness, depression or perceived stress, this association remained. Surprisingly, there was no evidence that poor sleep led to worse cognitive performance, thus causing more stress. Poor sleepers did just as well on the tests as the good sleepers (although I note that we cannot rule out that poor sleepers were having to put in more effort to achieve the same results). Although there was a tendency for poor sleepers to be in a worse mood after testing (perhaps because they had to put in more effort? My own speculation), this mood change didn’t predict the increased inflammatory response.

The findings add to evidence that poor sleep (unfortunately common as people age) is an independent risk factor for cognitive and physical health, and suggest we should put more effort into dealing with it, rather than just accepting it as a corollary of age.

REM sleep disorder doubles risk of MCI, Parkinson's

A recent Mayo Clinic study has also found that people with rapid eye movement sleep behavior disorder (RBD) have twice the risk of developing mild cognitive impairment or Parkinson’s disease. Some 34% of those diagnosed with probable RBD developed MCI or Parkinson's disease within four years of entering the study, a rate 2.2 times greater than those with normal REM sleep.

Earlier research has found that 45% of those with RBD developed MCI or Parkinson's disease within five years of diagnosis, but these findings were based on clinical patients. The present study involved cognitively healthy older adults (70-89) participating in a population-based study of aging, who were diagnosed for probable RBD on the basis of the Mayo Sleep Questionnaire.