Comparisons of cardiovascular dysautonomia and cognitive impairment between de novo Parkinson’s disease and de novo dementia with Lewy bodies

Abstract

Background Cognitive impairment may be correlated with cardiovascular dysautonomia, including blood pressure (BP) dysregulation, in Parkinson’s disease (PD), but the association between these factors in dementia with Lewy bodies (DLB) is uncertain. This study aimed to clarify whether cardiovascular dysautonomia had an influence on cognitive function in Lewy body disease or not. Methods 99 patients with de novo PD (n=75) and DLB (n=24) were evaluated using the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). Cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, orthostatic hypotension (OH), supine hypertension (SH), postprandial hypotension (PPH), nocturnal BP fall in 24-hour ambulatory blood pressure monitoring (ABPM) and constipation were estimated. Associations of these factors with cognitive and executive dysfunction were examined. Results In DLB, MIBG uptake was reduced and OH, PPH and SH were severely disturbed, compared to PD. The nocturnal BP fall in ABPM was lower in DLB, and the failure of nocturnal BP fall in PD was associated with MMSE, after adjustment for other clinical features. FAB was significantly associated nocturnal BP fall, age and SH in PD, but no significant correlations among factors were found for DLB. Conclusion The significant association between nocturnal BP dysregulation and cognitive or executive decline in PD might be due to impaired microvascular circulation or invasion of α-synuclein in the CNS. The lack of a correlation of BP insufficiency with cognitive impairment in DLB suggests initial involvement of Lewy body pathology in the neocortex, regardless of Lewy body invasion of the autonomic nervous system.

A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease

“…Furthermore, bilateral PNS-to-CNS invasion of pathology, due to overlapping bilateral vagal and sympathetic innervation of the gastro-intestinal (GI) tract, causes a more bilateral disease progression in the brain of these patients. This wider disseminated pathology, including more bilateral involvement of cerebral structures, could explain the well-documented faster symptomatic progression and accelerated dementia in clinical body-first Lewy body disease [27][28][29][30][31][32][33][34] . Note that the majority of patients with Dementia with Lewy bodies are probably bodyfirst, whereas only approximately 1/3 of PD patients show the body-first clinical phenotype 23,[35][36][37] .…”

“…Alzheimer co-pathology Table 3 summarizes the degree of neuritic plaque AD copathology in all (i.e., early to advanced) amygdala-predominant and in all brainstem/PNS-predominant cases from the two datasets. The cases are subdivided into four categories of global Lewy pathology burden scores (GBS): mild (1-10), moderate (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), severe (21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and very severe (31+).…”

“…In the brainstem/PNS-predominant groups, the mild (1-10) and moderate (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) GBS subgroups contained 50% and 38% CERAD stage B-C cases, respectively. The severe (21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and very severe (31+) subgroups contained 65% and 75% CERAD stage B-C cases, respectively.…”

“…Global Burden Scores (GBS) signify the summed burden of Lewy pathology. The amygdala-and brainstem/PNS-predominant cases in both datasets are divided into GBS categories of global mild (1-10), moderate(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), severe(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and very severe (31+) Lewy pathology. In each subgroup, the number of cases (n) with CERAD stage 0-A (none, mild) and B-C (moderate, severe) is listed.…”