Long-term atherogenic index of plasma (AIP) exposure and transition patterns in relation to dementia risk: A 23-year...

While dyslipidemia is implicated in dementia pathogenesis, the longitudinal relationship of the atherogenic index of plasma (AIP) and its transition patterns with dementia risk remains unclear.

9898 participants (aged 45-64) from the ARIC study (1987-2020) were included. Time-weighted cumulative AIP was calculated from serial measurements (Visits 1-3, 1987-1995). Cox models assessed associations between AIP metrics (quintiles, duration, and transition patterns) and incident dementia, adjusted for demographics, lifestyle, and clinical factors.

Over a median follow-up of 23.1 years, 2329 incident dementia cases were identified. Participants in the highest AIP quintile (≥0.27) had a 28 % increased dementia risk compared to those in lower quintiles (adjusted HR = 1.28, 95 % CI: 1.15-1.42). Age-stratified analyses revealed a stronger association in participants aged <55 years (P-interaction = 0.020). A duration-dependent effect was observed, where 6-year of high-AIP exposure was associated with increased dementia risk (adjusted HR = 1.19, 95 %CI: 1.03-1.37), and 9-year exposure conferred even greater risk (adjusted HR = 1.39, 95 %CI: 1.21-1.60). Transition pattern analyses showed that, compared to participants with consistently low AIP levels, those transitioning from low to high AIP had a 21 % increased risk (adjusted HR = 1.21, 95 %CI: 1.06-1.39), while those with persistently high AIP had a 35 % increased risk (adjusted HR = 1.35, 95 %CI: 1.19-1.54). Notably, individuals whose AIP decreased from high to low showed no significant increase in dementia risk.

Cumulative AIP exposure demonstrates dose-dependent associations with dementia risk, particularly in midlife. Sustained AIP elevation significantly increases dementia risk, whereas AIP reduction may mitigate this effect, highlighting its potential as a modifiable target for dementia prevention.