Spinal Lewy body pathology in older adults without an antemortem diagnosis of Parkinson's disease

Abstract

To test the hypothesis that Lewy body pathology (LBs) is present in the spinal cord of older community-dwelling adults without a clinical diagnosis of Parkinson's disease (PD). We studied 162 prospective autopsies from older adults with PD (N = 6) and without PD (N = 156). We documented the presence of LBs in cerebrum and brainstem structures from each of the six regions used for Braak PD staging and four spinal cord levels (C5/6, T7, L4/5 and S4/5). Parkinsonism proximate to death was based on a previously validated measure present if two or more of the four signs of parkinsonism were present based on a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS). Fifty-three of 156 individuals without PD (34%) had LBs in a least one site within the CNS. About half of cases with LBs in the cerebrum or brainstem, (25/53, 47%) also had spinal LBs. Almost 90% (22/25, 88%) of cases with spinal LBs had LBs in the cerebrum (Braak stages 4-6) and about 10% (3/25, 12%) had only brainstem LBs (Braak stages 1-3). Four of six cases with PD showed LBs in cerebrum, brainstem and spinal cord. Individuals with LBs in the spinal cord were more likely to have clinical parkinsonism proximate to death compared to individuals with LBs in brainstem and cerebrum alone (52% vs. 32%; Chi-Square x = 5.368, d.f. = 1, P = 0.0.021) and more severe nigral neuronal loss (48% vs. 11%; Chi-Square x = 9.049, d.f. = 1, P = 0.003). These findings were unchanged when we included cases with a history of PD. Older community-dwelling adults without a clinical diagnosis of PD have evidence of LBs throughout the CNS including the spinal cord which is associated with parkinsonism and more severe nigral neuronal loss.

Brain pathology is related to total daily physical activity in older adults

“…[31][32][33] Thus, to determine the full extent to which age-related CNS pathologies underlie total daily physical activity, it is likely to be necessary to examine postmortem indexes in motor regions outside the brain. [34][35][36] It is also possible that the construct of total daily physical activity may not be related to indexes of brain pathologies, as we have reported for other constructs of volitional late-life activities such as the frequency of cognitive activities. 37,38 Prior studies suggest that the improved brain health manifested by individuals with higher levels of physical activity may derive from better structural brain integrity, neuroplasticity, and angiogenesis, but the mechanisms underlying these changes are unknown.…”

Spinal motor neurons and motor function in older adults

“…[6, 9] Together these studies provide evidence that not only brain pathologies but also the accumulation of neuropathologies in the spinal cord as well as degeneration of spinal cellular elements may make independent contributions to loss of motor function in older adults without overt neurologic diseases. To translate these findings into the clinical setting, further work is needed to determine the molecular pathways underlying these spinal cord changes and to what degree these mechanisms are region specific.…”

“…[14] These data suggested that postmortem indices from outside the cerebrum might account for some of this unexplained variance. [7, 9, 10]…”

“…Recent work in this cohort suggests arteriolosclerosis and Lewy body pathology accumulate in the spinal cord and are related to poorer motor function in older adults. [7, 9] Thus, loss of SMNs in older adults may be due in part to the presence of unrecognized spinal neuropathologies. Accumulating evidence suggests that activated microglia may contribute to ALS, a degenerative disorders characterized by the loss of SMN.…”

Neocortical Lewy bodies are associated with impaired odor identification in community-dwelling elders without clinical PD

“…Pathological studies of the olfactory bulb and tract in PD demonstrate phosphorylated αsynuclein immunoreactive neuronal intracytoplasmic Lewy bodies (LBs) and dystrophic Lewy neurites [16][17][18][19]. Localization of LB pathology in the olfactory bulb is also reported in a majority of cases of DLB [20] and incidental LB disease, (ILBD) [16,[20][21][22][23][24] in which the clinical features of PD are not present and which may represent the preclinical form of PD [7,25,26]. Extension of LB pathology beyond the olfactory bulb, in primary olfactory cortices including the olfactory tubercle, the frontal and temporal piriform cortices has also been reported in PD and ILBD [27,27].…”