Risk factors and predictors for Lewy body dementia: a systematic review

Area of Science:

• Neurology
• Neuroscience
• Geriatrics

Background:

• Lewy body dementia (LBD), encompassing Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), represents a significant and challenging neurodegenerative condition.
• Understanding the factors that predispose individuals to LBD is essential for elucidating its underlying mechanisms and developing targeted therapeutic strategies.

Purpose of the Study:

• To systematically review and synthesize findings from longitudinal studies that identify risk factors and prodromal markers for Lewy body dementia.
• To consolidate evidence on factors preceding the onset of LBD in individuals without dementia at baseline.

Main Methods:

• A comprehensive systematic review was conducted, searching major databases (PubMed, Embase, Web of Science).
• Included studies were longitudinal, assessed risk/prodromal factors for LBD, enrolled participants without baseline dementia, and were of good/high methodological quality (Newcastle-Ottawa Scale).

Main Results:

• 167 studies were included, identifying numerous consistently reported risk factors.
• Key predictors include older age, male sex, APOEε4 genotype, GBA mutations, and a range of clinical manifestations such as cognitive changes, mood disturbances, sleep disorders, gait abnormalities, parkinsonism, and olfactory loss.
• Biomarkers like white matter disease on MRI, reduced CSF amyloid β42, and elevated CSF/blood neurofilament light chain were also noted.

Conclusions:

• Older age, male sex, genetic predispositions, and specific clinical and biomarker changes are associated with an increased risk of developing LBD.
• The current evidence base predominantly features cohorts from North America and Europe, with a focus on PDD, necessitating broader, more diverse research populations to enhance generalizability and improve risk prediction for all forms of LBD.