Clinical correlates of pathology in the claustrum in Parkinson's disease and dementia with Lewy bodies

Dementia and visual hallucinations are common complications of Parkinson's disease (PD), yet their patho-anatomical bases are poorly defined. We studied α-synuclein (αSyn), tau and amyloid-β (Aβ) pathology in the claustrum of 20 PD cases without dementia, 12 PD cases with dementia (PDD) and 7 cases with dementia with Lewy bodies (DLB). αSyn positivity was observed in 75% of PD cases without dementia and in 100% of PDD and DLB cases. Aβ was observed in the claustrum in 25% of PD, 58% of PDD and 100% of DLB cases. Tau was negligible in all cases restricting further analysis. Compared to PD cases without dementia, PDD cases demonstrated a significantly greater αSyn burden in the claustrum (p = 0.0003). In addition, DLB cases showed a significantly increased αSyn deposition when compared to PDD (p = 0.02) and PD without dementia (p = 0.0002). A similar hierarchy, PD < PDD < DLB was seen in terms of Aβ burden in the claustrum. Comparison of αSyn and Aβ burden in those cases with and without visual hallucinations did not reveal any significant associations (p = 0.13 and 0.1, respectively). We demonstrate that pathology in the claustrum, a region of largely obscure physiological function, strongly relates to the presence of dementia in Parkinson's disease and DLB.