Although motor impairments in Parkinson disease are attributed to nigrostriatal dopaminergic denervation, postural instability and gait difficulty (PIGD) features are less responsive to dopaminergic medications. PIGD features are a risk factor also for development of dementia in Parkinson disease. These observations suggest that non-dopaminergic mechanisms may contribute to axial motor impairments. The objective was to perform a correlative positron emission tomography study to examine the relationship between neocortical β-amyloid deposition ([¹¹C]-Pittsburgh Compound-B), nigrostriatal dopaminergic denervation ([¹¹C]-dihydrotetrabenazine), and PIGD feature severity in Parkinson disease patients at risk for dementia.

Cross-sectional study of 44 Parkinson disease patients (11 Female / 33 Male; 69.5 ± 6.6 years; 7.0 ± 4.8 years motor disease duration; mean Hoehn and Yahr stage 2.7 ± 0.5) who underwent positron emission tomography, motor feature severity assessment using the Movement Disorder Society revised Unified Parkinson's Disease Rating Scale, and the Dementia Rating Scale.

Linear regression (R²_adj=0.147, F_4,39=2.85, p=0.036) showed that increased PIGD feature severity was associated with increased neocortical [¹¹C]-Pittsburgh Compound-B binding (β=0.346, t₃₉=2.13, p=0.039), while controlling for striatal [¹¹C]-dihydrotetrabenazine binding, age, and Dementia Rating Scale total score.

Increased neocortical β-amyloid deposition, even at low range levels, is associated with higher PIGD feature severity in Parkinson disease patients at risk for dementia. This finding may explain why the PIGD motor phenotype is a risk factor for development of dementia in Parkinson disease.