In 353 healthy older Germans, fitness was linked to some brain-scan measures but not to test scores

Exercise is often named as a way to keep the brain healthy in old age. But many studies behind that idea asked people how much they exercise, and people do not always report this accurately. A team at the German Center for Neurodegenerative Diseases (DZNE) in Magdeburg instead measured fitness directly, and then compared it with a wide range of brain measurements in older adults whose memory and thinking were normal.

The researchers had two ideas in mind. The first is brain maintenance: fitter people might simply collect less damage in the brain as they age. The second is cognitive reserve: fitter people might cope better with damage that is already there, so it hurts their memory less.

What they did

The study used the first visit of an ongoing study in Magdeburg. It included 353 people aged 60 to 94 (on average about 73; 177 women), all living independently and fairly highly educated. Nobody had signs of memory problems, a neurological or psychiatric illness, diabetes or another major disease.

Everyone's muscular fitness was measured with three tests combined into one score: grip strength, muscle mass in the arms and legs (estimated with a small electrical current through the body), and the Timed Up and Go test, which times how fast a person stands up from a chair, walks a short distance, turns and sits back down.

A subgroup of 140 people also did a cycling test to exhaustion that measures VO₂max, the largest amount of oxygen the body can use per minute. It is the standard measure of aerobic fitness, the kind of fitness that running or cycling builds. Only people who could safely do such a test took part, so this subgroup was even healthier than the rest.

The team then gave memory and thinking tests and looked at:

• MRI brain scans (about 240–260 people): the volume of gray matter, the brain tissue that holds most nerve cell bodies; the thickness of the medial temporal lobe, an area important for memory that shrinks early with age; small spots of damage in the white matter; and perivascular spaces, tiny fluid-filled channels around blood vessels that tend to widen with age and with vessel disease.
• PET scans (143 people) showing tau, a protein that forms tangles inside nerve cells in Alzheimer's disease.
• Blood markers of Alzheimer's-type changes and of brain "plasticity", the brain's ability to adapt.

All results were adjusted for age, sex and years of education.

What they found

• No link with test scores. Neither muscular nor aerobic fitness was linked to better memory or overall thinking scores. The team's first hypothesis was not supported.
• Muscle function and fluid channels. Higher muscular fitness was linked to a smaller volume of widened perivascular spaces in the basal ganglia, a group of structures deep in the brain. Within the muscle score, this came from the chair-and-walk test. Aerobic fitness showed a similar but weaker trend that did not hold up once the team corrected for the many comparisons.
• Aerobic fitness and brain size. People with higher VO₂max had more total gray matter and a thicker medial temporal lobe.
• No link with Alzheimer's markers. Fitness was not linked to the tau scans or to the Alzheimer's blood markers, nor to the plasticity markers.
• A weak hint of reserve. More tau in the medial temporal lobe was linked to poorer recall of a word list. Fitness did not soften that link. But when tau was taken into account, higher VO₂max was linked to better word recall and explained an extra 7.6% of the differences between people. The authors call this only "weak evidence" for cognitive reserve.
• A surprise. Higher muscle mass was linked to smaller brain volumes. The authors suspect muscle mass partly reflects body size here, since it tracked with body mass index and did not go together with grip strength or the walking test.

What to keep in mind

• A single snapshot. The authors stress that the design "precludes causal inference". The links could run the other way: early, unnoticed brain or blood-vessel changes might make people slower and weaker. Shared risk factors could also affect both.
• A very healthy, uniform group. Participants were highly educated, white German adults without major disease, and the VO₂max group was healthier still. The narrow range of fitness and test scores may have hidden small effects, and the results may not apply to other people.
• Smaller subgroups. Tau scans and plasticity markers (under 90 people) were available only for some participants, which weakens those analyses. The authors ask readers to treat the "no effect" findings with caution.
• Some results are borderline. The gray matter and thickness results were not corrected for multiple comparisons, and the surprising muscle-mass results were isolated and need repeating.
• Fitness was measured once; balance and flexibility were not tested.

Why it matters

Using measured rather than self-reported fitness, this study found no sign that fitter older adults did better on memory tests, but it did find that fitness was linked to some features of a healthier-looking brain. The authors see this as broadly fitting the idea of brain maintenance, with little support for cognitive reserve. Whether improving fitness actually changes the brain can only be answered by studies that follow people over time or test exercise programmes, which the authors say are now needed.