Gene variant linked to better thinking in Parkinson’s disease
An observational analysis of two Parkinson’s cohorts, with 354 and 83 people genotyped, linked a gene variant to better scores on specific thinking tests.
Cohort study, independent replication
Limit: Cognitive decline over time was not measured; thinking tests were taken only at baseline
Edited by Boris Djordjevic · AgingResearch.News
Researchers analyzed baseline thinking tests in two observational cohorts of people with early-stage Parkinson’s disease, with 354 and 83 participants genotyped. They compared people carrying one copy of a KLOTHO gene variant with noncarriers, excluding those with two copies. Participants were not taking drugs that act on dopamine, a brain signaling chemical.
The variant, linked to higher blood levels of the protein klotho, was associated with better executive function—thinking skills including working memory—in both cohorts. It was not associated with better movement function after adjustment for other factors. Separately, genetic engineering to raise klotho levels extended lifespan and improved memory-test performance in male mice expressing human alpha-synuclein, a protein. It did not improve their movement function.
Why it matters
Cognitive impairment is a major challenge in Parkinson’s disease, for which aging is the primary risk factor. The authors suggest klotho may point toward new therapeutic pathways.
Caveats
The human analysis used baseline observations, so it cannot show that the variant prevented cognitive decline or that raising klotho would help patients. The human findings concern early-stage Parkinson’s disease; the animal experiments used only male mice.
The paper
University of California, San Francisco
The Journal of Neuroscience, Apr 1, 2026, Open access
