Healthy lifestyle may blunt dementia risk even for genetically vulnerable
A major study of 437,000 people found that those carrying genetic risk factors for type 2 diabetes faced sharply higher dementia risk—but only if they neglected basic health habits. People maintaining good diet, exercise, sleep, and other lifestyle markers stayed protected across all genetic risk levels, suggesting interventions could help even the most at-risk populations.
Originaltitel: Life's Essential 8, Polygenic Risk for Type 2 Diabetes, and Dementia: Evidence from the UK Biobank.
Genetisk risk för typ 2-diabetes kopplas till demensrisk, men det går att motverka genom hälsosam livsstil. Svenska forskare från Karolinska Institutet och GIH analyserade 437 732 personer från UK Biobank under i genomsnitt 13,3 år och fann 9 425 demensfall. En tydlig dos-responsrelation visades mellan polygent riskscore för diabetes och vaskulär demens, med kraftigt ökad risk över 95:e percentilen. Deltagare med låga livsstilspoäng (Life's Essential 8) hade genomgående högre demensrisk än de med moderate till höga poäng, oberoende av genetisk predisposition. Resultaten tyder på att beteendeförändringar—träning, kost, sömn, rökning—kan reducera demensrisken även hos genetiskt högriskindivider. För farmakologiska och preventiva interventioner betyder detta en marknad för lifestyle-baserad riskstratifiering och personaliserad demensförebyggande vård.
BACKGROUND/OBJECTIVES: It is unclear if adherence to healthy guidelines can modify the association between polygenic risk score (PRS) for type 2 diabetes and dementia. This study aimed to investigate interrelationships between PRS for type 2 diabetes, Life's Essential 8 (LE8) metrics, and dementia. METHODS: We included 437,732 UK Biobank participants aged ≥40 years between 2006 and 2010. PRS for type 2 diabetes was calculated by summing weighted genetic variant effects. Incident all-cause and cause-specific dementias were identified using registry records up to December 2022. LE8 scores were classified as low vs. moderate-to-high levels. Cox regression and restricted cubic splines were applied. RESULTS: Over an average follow-up of 13.27 years (SD = 2.27), 9425 participants developed dementia. A dose-response relationship was observed between PRS and vascular dementia, with risk rising sharply beyond the 95th percentile. Individuals with low LE8 constantly showed a higher risk of all-cause dementia than those with moderate-to-high LE8 across all values of PRS for type 2 diabetes. CONCLUSIONS: A dose-response relationship exists between PRS for type 2 diabetes and dementia, particularly vascular dementia. Adherence to optimal LE8 metrics, particularly behavioral components, may contribute to dementia prevention across genetic strata. These findings highlight the importance of multidomain lifestyle interventions in dementia prevention.