Modifiable dementia risk associated with smaller white matter volume and altered 1/f aperiodic brain activity: cross-sectional insights from the LEISURE study.

Background: The rising prevalence of dementia necessitates identifying early neurobiological markers of dementia risk. Reduced cerebral white matter volume and flattening of the slope of the electrophysiological 1/f spectral power distribution provide neurobiological markers of brain ageing alongside cognitive decline. However, their association with modifiable dementia risk remains to be understood.

Methods: A cross-sectional sample of 98 healthy older adults (79 females, mean age = 65.44) underwent structural magnetic resonance imaging (sMRI), resting-state electroencephalography (EEG), cognitive assessments and dementia risk scoring using the CogDrisk framework. Univariate and multivariate linear regression models were conducted to investigate the relationships between modifiable dementia risk and sMRI brain volumes, the exponent of EEG 1/f spectral power, and cognition, whilst controlling for non-modifiable factors.

Results: Smaller global white matter volume (F(1,87) = 6.884, R2 = 0.073, P = .010), and not grey (F(1,87) = 0.540, R2 = 0.006, P = .468) or ventricle volume (F(1,87) = 0.087, R2 = 0.001, P = .769), was associated with higher modifiable dementia risk. A lower exponent, reflecting a flatter 1/f spectral power distribution, was associated with higher dementia risk at frontal (F(1,92) = 4.096, R2 = 0.043, P = .046) but not temporal regions. No significant associations were found between cognitive performance and dementia risk. In multivariate analyses, both white matter volume and the exponent of the 1/f spectral power distribution independently associated with dementia risk.

Conclusions: Structural and functional neurobiological markers of early brain ageing, but not cognitive function, are independently associated with modifiable dementia risk in healthy older adults.