First Signs of Memory Problems Linked to Tau Changes in the Brain

People who report early memory problems and whose partners also suspect they have memory problems have higher levels of tau tangles in the brain, a biomarker associated with Alzheimer’s disease, according to a study published online in Neurology.

Subjective cognitive decline is when a person reports memory and thinking problems before any decline is large enough to show up on standard tests.

“Understanding the earliest signs of Alzheimer’s disease is even more important now that new disease-modifying drugs are becoming available,” said study author Rebecca E.  Amariglio, PhD, of Harvard Medical School in Boston. “Our study found early suspicions of memory problems by both participants and the people who knew them well were linked to higher levels of tau tangles in the brain.”

The study involved 675 adults with an average age of 72 who did not have cognitive impairment on formal testing. All had brain scans for amyloid plaques. Of this group, 60% had elevated levels of amyloid, meaning they were at risk for developing cognitive impairment due to Alzheimer’s disease even though, at the time of the scan, they were cognitively normal. Participants did not know if they had elevated levels of amyloid.

Each participant had a study partner—a spouse, child or friend—who could answer questions about the participant’s thinking and memory skills and ability to perform daily tasks. In 65% of cases, partners lived with participants.

Each participant and their partner completed a questionnaire to assess the participant’s subjective cognitive decline. Questions included, “Compared to one year ago, do you feel that your memory has declined substantially?” and “Compared to one year ago, do you have more difficulty managing money?” Participants’ and partners’ scores were recorded with higher scores indicating greater complaints about memory.

Researchers also reviewed brain scans for levels of tau tangles. Greater tau is also a risk factor for Alzheimer’s disease and is at higher levels in people with elevated amyloid.

Researchers found participants with higher levels of tau tangles in the brain had higher scores of complaints on the memory questionnaire. Their partners also scored them higher. This association was stronger in participants who had elevated levels of amyloid plaques.

“Our study included a high percentage of people with elevated amyloid, and for this reason we were able to also see that memory complaints were associated with higher tau tangles," said Amariglio. “Our findings suggest that asking older people who have elevated Alzheimer’s disease biomarkers about subjective cognitive decline may be valuable for early detection. This is particularly important since it is predicted that treatments given at the earliest diagnosable form of the disease will be the most effective in slowing the disease.”

Limitations of the study include that most participants were white and highly educated. Amariglio noted future studies should follow people for longer periods of time and include more participants from other racial and ethnic groups, as well as people with different levels of education.