Spinal Arteriolosclerosis Is Common in Older Adults and Associated With Parkinsonism

Abstract

Background and purpose: There are few studies of spinal microvascular pathologies in older adults. We characterized spinal cord microvascular pathologies and examined their associations with other spinal and brain postmortem indices and parkinsonism in older adults.

Methods: We documented 3 features of microvascular pathologies in spinal cord and brain specimens from 165 deceased older participants. We also measured spinal white matter pallor. Parkinsonian signs were assessed with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. We examined the associations of spinal arteriolosclerosis with other spinal and brain postmortem indices and parkinsonism proximate to death using regression models which controlled for age and sex.

Results: Microinfarcts and cerebral amyloid angiopathy were not observed within the spinal cord parenchyma. Spinal arteriolosclerosis was observed at all spinal levels (C7, T7, L4, S4) examined and was more severe posteriorly than anteriorly (posterior: 4.3, SD=0.72 versus anterior: 3.9, SD=0.74; t=14.58; P<0.001). Arteriolosclerosis was more severe in the spinal cord than in the brain (cord: 4.10, SD=0.70; brain: 3.5, SD=0.98; t=10.39; P<0.001). The severity of spinal arteriolosclerosis was associated with spinal white matter pallor (r=0.47; P<0.001). Spinal arteriolosclerosis accounted for ≈3% of the variation in parkinsonism in models controlling for age, sex, brain arteriolosclerosis, and cerebrovascular disease pathologies. Further models showed that the association of spinal arteriolosclerosis and parkinsonism was not mediated via spinal white matter pallor.

Conclusions: Although the regional distribution of microvascular pathologies varies within the central nervous system, spinal arteriolosclerosis is common and may contribute to the severity of spinal white matter pallor and parkinsonism in older adults.

Keywords: aging; arteriolosclerosis; cerebrovascular disease; parkinsonism; spinal cord.

Figure 1. Spinal Arteriolosclerosis

The spectrum of arteriolosclerosis observed in the cervical spinal cord is illustrated: no arteriolosclerosis, grade 0 (A), mild, grade 2 (B), moderate, grade 4 (C) and severe arteriolosclerosis, grade 6 (D). Original magnification × 200.

Figure 2. Spinal and Brain Arteriolosclerosis

Photomicrographs depict the similarity of the arteriolosclerosis grades in the cervical spinal cord and anterior watershed region of the brain. Spinal cord photomicrographs from Figure 1 show no arteriolosclerosis, grade 0 (A) and severe arteriolosclerosis, grade 6 (B). Similar caliber vessels in the brain show no arteriolosclerosis, grade 0 (C) and severe arteriolosclerosis, grade 6 (D). Original magnification × 200.

Figure 3. Spinal White Matter Pallor

The locations of the spinal regions (PC, LCR and LCL) in which we measured white matter pallor in the cervical spinal cord (A) are shown in relation to spinal grey matter. The spectrum of white matter pallor observed in the cervical spinal cord is illustrated: mild, grade 2, (B) moderate, grade 4 (C) and severe, grade 6 (D) white matter pallor in both gracile fasiculi of the posterior columns (PC) in the Luxol Fast blue-hematoxylin and eosin stained sections. The pallor extends into the cuneate fasiculi in the cross section (D) of the cervical cord. LCR= right lateral column and LCL= left lateral column, AH= anterior horn, PH=posterior horn. Original magnification B–D × 25.

Figure 4. Spinal Arteriolosclerosis is Associated with White Matter Pallor and Parkinsonism in Older Adults

On the left (A), a scatter plot illustrates that more severe spinal arteriolosclerosis is associated with more severe spinal white matter pallor. On the right (B) a scatter plot shows that more severe spinal arteriolosclerosis is related to more severe parkinsonism proximate to death.