A lifestyle program helped thinking in older adults whatever their Alzheimer’s blood markers said

Alzheimer’s disease begins in the brain decades before anyone notices memory problems. Two proteins build up: amyloid, which forms sticky plaques between nerve cells, and tau, which forms tangles inside them. Until recently, seeing this meant a brain scan or a spinal tap. Now blood tests can pick up traces of it. The most promising measures a form of tau called p-tau217. Others track nerve damage (NfL, neurofilament light) or irritated support cells in the brain (GFAP).

This raises a practical question. Lifestyle programs that combine healthy eating, exercise, mental training and care of blood pressure and cholesterol have been shown to slow mental decline in older adults at risk. But do they still help people whose brains already show early Alzheimer’s changes? And does such a program change those changes?

What they did

The team went back to FINGER, a Finnish randomized trial and one of the first large studies to show that this kind of program improves thinking skills. Between 2009 and 2011 it enrolled 1,260 people aged 60 to 77 who scored high on a dementia risk score but had no dementia and no serious memory problems. Half were assigned at random to a two-year program delivered by a team of health professionals: diet counselling, strength and aerobic training, group sessions and computer-based brain training, and regular checks of blood pressure, blood fat, blood sugar and weight. The other half received regular health advice. A detailed battery of 14 tests measured thinking skills at the start, after one year and after two years.

Blood samples taken at the start and at two years had been frozen. In 2024 they were sent off to test for a panel of Alzheimer’s markers, including p-tau217 with a test already used in some clinics. The researchers asked three questions: do the markers predict how a person’s thinking changes; does the program work equally well at different marker levels; and does the program change the markers?

What they found

• Most participants had normal markers. About 85% had p-tau217 below the level considered abnormal; 8% were in a grey zone and 6.6% above it.
• Higher markers went with poorer thinking. Across both groups, people with higher levels of several markers did worse at the start, and higher levels of almost all of them went with less improvement over two years. Those with abnormal p-tau217 had roughly twice the odds of a decline in memory.
• But the markers were weak at spotting amyloid. In the 46 people who also had an amyloid brain scan, p-tau217 sorted those with and without plaques only moderately well (an accuracy score, AUC, of 0.72 to 0.75, where 1 is perfect and 0.5 is a coin toss).
• The program helped across marker levels. Statistically, the benefit of the program did not depend on any marker. The difference between the program and the control group pointed in favour of the program both in people with lower and with higher levels.
• The markers barely moved. Over two years they rose a little in both groups, as expected with age. The rise was the same with or without the program, and the same in people who attended more or fewer sessions. After two years, 82% were still in the normal range for p-tau217.

What to keep in mind

• Not yet peer-reviewed. This is a preprint.
• A follow-up analysis. FINGER was designed to test the program’s effect on thinking, which it showed years ago. Whether markers modify that effect is a secondary question. Some subgroup results hinted at a larger benefit in people with lower p-tau and GFAP, but the authors say these patterns were “not fully consistent” and should be read “with caution”.
• Two years may be too short. Since most people started with normal markers and few crossed into the abnormal range, the authors note that the time frame may be too brief to see the program change brain disease, if it does.
• One test platform is new. Most markers were measured with a newer method that gives relative, not absolute, amounts, which makes comparison with other studies harder.
• Small scan group, one country. Only 46 people had a brain scan, and all participants were Finnish. The authors call for studies in more diverse populations.

Why it matters

The finding has two sides. The encouraging one: a broad lifestyle program supported thinking skills even in people who already showed early Alzheimer’s signs in their blood, so these markers are not a reason to exclude anyone from such programs. The sobering one: the program did not change the markers, so whatever helps the brain probably works through other routes. The authors suggest blood vessels, metabolism, inflammation or “cognitive reserve”, the brain’s ability to cope with damage. A similar US trial, POINTER, also found no effect on amyloid or tau brain scans. And for healthy older people, the blood tests seem better at flagging who may decline than at diagnosing Alzheimer’s on their own.