Parkinson’s disease with dementia falls into two pathologic subgroups

By Andrew Czyzewski, MedWire Reporter

Patients with Parkinson's disease (PD) who also have dementia fall into two main pathologic categories, characterized by neocortical synucleinopathy in isolation and neocortical synucleinopathy with amyloid beta (Aβ) deposition.

Importantly, the latter group of patients with Aβ deposition showed a shorter survival than their peers with only synucleinopathy.

"Defining such pathologic subtypes is particularly important for designing interventions that target specific pathologic protein species, such as anti-Aβ therapies," Paul Kotzbauer (Washington University School of Medicine, St Louis, Missouri, USA) and colleagues comment in the Archives of Neurology.

For the study, they collected autopsy information from 32 PD patients with dementia who died between February 2005 and July 2010. Histologic and immunohistochemical analysis were used to determine the distribution and severity of individual pathologic protein deposits of α-synuclein, Aβ, and tau.

Meanwhile, clinical data were extracted from an electronic medical record system used for all patients with PD.

Kotzbaur et al report that all 32 patients with PD and dementia had cortical synucleinopathy (Braak Lewy body stage 5‑6).

In addition 19 of those patients had cortical synucleinopathy as well as substantial cortical Aβ but no or minimal neocortical tau deposition (synuclein plus Aβ). Twelve patients had only cortical synucleinopathy without substantial Aβ or tau (synuclein only).

Only one patient had neocortical synucleinopathy, Aβ, and tau deposition, and who, as a consequence, met established criteria for "definite" or "high likelihood" Alzheimer's disease (AD) contributing to dementia.

No significant differences were found between synuclein plus Aβ versus synuclein only for any clinical features, including hallucinations, lethargy, last Unified PD Rating Scale score, lowest Mini-Mental State Examination score, and Ascertain Dementia 8 score.

However, the synuclein-only subtype group lived significantly longer after PD onset and after dementia onset than their peers with synuclein plus Aβ (hazard ratio=0.51 and 0.52, respectively).

Discussing the findings, Kotzbaur et al note that tauopathy is a hallmark of AD pathology but based on the present data "is not a major contributor to dementia associated with PD."

They conclude: "Further support for the role of Aβ would provide rationale for testing therapeutic approaches for reducing Aβ accumulation that, so far, have focused on AD."

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