Neuropathology in Parkinson’s disease with mild cognitive impairment

Abstract

In a recent paper, Adler et al. [1] reported the neuropathologic findings in eight cases of Parkinson disease with mild cognitive impairment (PD-MC) (6 males, 2 females, mean age 82.8 years, mean PD duration 11.4 years). Four patients each had amnestic MCI memory only, three non-amnestic MCI with frontal executive and one with frontal executive and visuospatial dysfunctions. Using the Unified Lewy Body Staging System (ULBSS [2]), three cases each were brainstem-predominant (stage IIa), and brainstem–limbic predominant (stage III), and two neocortical LB stage (stage IV), while two PD cases with non-amnestic and one with amnestic MCI showed additional multiple brain infarcts. These data suggested a heterogenous neuropathology of PD-MCI, as found in Parkinson disease dementia (PDD). Unfortunately, no assessment of diffuse (amyloid) plaques and cerebral amyloid angiopathy (CAA) was performed, the impact of which on cognitive dysfunction in Lewy body diseases (LBDs) has been shown [7, 8]. Among 233 autopsy-confirmed cases of LBDs in the years 1989–2007 (54.6% cognitively unimpaired, 42% PDD), we found eight cases (3.4%) with PD-MCI (4 females and males each, mean age 76.6 years, mean duration of PD 13.4 years; mini-mental examination scores/ MMSE, 6–4 months prior to death 26–29). Demographic and morphologic findings are summarized in Table 1. Using current definitions of MCI in PD [5], four patients had been diagnosed with amnestic MCI memory only, three with non-amnestic MCI with frontal dysexecution, and one MCI involving multiple domains. Neuropathology revealed two cases in brainstem-predominant stage (Braak et al. [3, 4], ULBSS 2a [2]), five cases in brainstem–limbic predominant stage (Braak et al. [4], ULBSS 3), and one in neocortical LB stage (Braak et al. [5], ULBSS 4). Neuritic Braak stages ranged from I to III (mean 1.3); a few neuritic plaques in cerebral cortex (neocortex and limbic areas) were observed in only two cases (amnestic–memory predominant MCI and MCI multidomains). The severity of amyloid plaques in cerebral cortex, using a five-grading system [6, 7] ranged from 0 to 3? (mean 1.1), involving three cases. No diffuse amyloid plaques were observed in the basal ganglia. Mild to moderate generalized CAA in the meninges was observed in two brains (amnestic and multiple domain MCI, one each). In the case of MCI involving multiple domains, there was a correlation between the intensity of amyloid and neuritic plaques and meningeal CAA, while the other case showed some relations between amyloid plaque load and CAA confirming the suggestion that both amyloid plaque load and CAA may contribute to cognitive impairment in Lewy body disease or PD [7]. Mild lacunar state in striatum or thalamus was detected in three cases (one each with amnestic, non-amnestic, and multiple domains MCI), both without correlation to Lewy body or Alzheimer pathology stages, confirming the absence of correlations between cerebrovascular lesions and the other pathologic or clinical findings in PD [6]. The presently available scarce data in PD-MCI suggest a heterogenous neuropathology simular to those found in MCI cases without PD [9, 11–14], except the scarcity of cerebrovascular pathology and white matter lesions (data not shown) in the present series. MCI stages and their neuropathologic correlations in dementia with Lewy bodies (MCI-DLB [10]), to the best of our knowledge, have not been defined so far. The findings of these two small clinicopathologic cohorts of PD-MCI implicate the necessity for further prospective studies in well documented PD cases with MCI. K. A. Jellinger (&) Institute of Clinical Neurobiology, Kenyongasse 18, 1070 Vienna, Austria e-mail: kurt.jellinger@univie.ac.at