Summary
A six-month pilot in 138 cognitively normal adults used family history, genetics and plasma pTau217 to identify people at higher Alzheimer’s risk. Participants who received personalised lifestyle coaching reported less worry, while cognitive scores and lifestyle-risk measures remained unchanged and pTau217 showed only a slower rise.
A six-month pilot study in north Alabama tested whether Alzheimer’s disease risk screening using family history, genetics and a blood biomarker could be combined with personalised lifestyle coaching for older adults who had no measurable cognitive impairment. The medRxiv preprint found that participants reported less worry and lower perceived dementia risk after disclosure and coaching, while cognitive scores and lifestyle-risk indices were unchanged over the study period.
The study was designed as an early feasibility assessment, not as a test of whether the programme prevents Alzheimer’s disease. Its findings provide short-term information about risk disclosure, participant attitudes and selected measurements in a high-risk group.
Contents
How participants were screened
The researchers recruited cognitively normal adults aged 65 to 75 in north Alabama who had a first-degree relative with Alzheimer’s disease or dementia. A total of 138 people were screened using the Montreal Cognitive Assessment, family history, APOE genotyping, a non-APOE Alzheimer’s disease polygenic risk score and plasma pTau217.
APOE genotyping and a polygenic risk score provide genetic information related to inherited susceptibility. Plasma pTau217 is a blood-based biomarker used in Alzheimer’s research to help assess disease-related risk. In this pilot, the researchers combined these measures into a composite risk rubric.
Participants were classified as high risk when their composite score was above 5 and/or their plasma pTau217 level exceeded 0.18 pg/mL. Fifty-two of the 138 screened participants, or 37.7%, met that definition. Most of those classified as high risk—69.2%—were identified through pTau217 alone.
High-risk participants received disclosure of their results and entered a personalised six-month intervention involving dietitian-led coaching, cognitive training and activity tracking. The researchers assessed attitudes toward dementia risk before and after disclosure, measured distress using the REVEAL IGT-AD scale, and collected cognitive, lifestyle and biomarker measurements.
What changed during six months
Before risk disclosure, participants’ subjective perceptions of dementia risk were correlated with their objective risk scores. After disclosure and during the intervention, self-reported worry and perceived dementia risk decreased significantly.
The results also showed that risk information could produce distress for some participants. Scores consistent with clinically significant distress appeared in 28% of survey respondents at at least one timepoint. The authors report that 50% of these distress observations occurred in people with pre-existing anxiety or depression.
The biological and cognitive measurements changed less. Montreal Cognitive Assessment scores and lifestyle-risk indices were unchanged over six months. Plasma pTau217 continued to rise, but the researchers reported that its rate of increase was slower than during the interval between initial screening and the start of the lifestyle intervention.
That pattern is an early biomarker observation rather than a clinical outcome. The study did not measure whether participants developed dementia or whether the intervention reduced future Alzheimer’s disease incidence.
Why the findings are preliminary
The report is a pilot preprint based on a selected group of cognitively normal older adults from one region of Alabama, all of whom had a close family history of dementia. The intervention period lasted six months, and the reported outcomes mainly concern attitudes, cognitive screening, lifestyle measures and pTau217 trajectories.
The study is therefore best understood as evidence that a genomics- and biomarker-informed screening and coaching model can be implemented in this high-risk setting, with generally manageable distress and improved attitudes after disclosure. Whether the slower pTau217 rise would persist, whether lifestyle measures would change with longer follow-up, and whether the approach could lower clinical Alzheimer’s risk require larger, longer and more diverse studies.
The authors describe the findings as support for further trials validating this model for Alzheimer’s screening. The preprint reports ethical approval from the WCG Institutional Review Board and lists the prospective study under ClinicalTrials.gov identifier NCT07146412.