Arteriolosclerosis in CNS Tissues Outside the Cerebrum and Late-Life Motor Impairment

The pathological basis underlying motor impairment in older adults is partially accounted for by Alzheimer disease and related dementias pathologies. We tested the hypothesis that arteriolosclerosis, a pathological correlate of small vessel disease, outside the cerebrum is related to motor impairment in older adults above and beyond Alzheimer disease and related dementias pathologies.

The data were from decedents of a community-based clinical-autopsy study. Arteriolosclerosis was assessed in the cerebrum (as 1 of 10 Alzheimer disease and related dementias pathologies), midbrain, cerebellum, pons, and 4 levels of the spinal cord. Parkinsonism was assessed using the Unified Parkinson Disease Rating Scale. Other motor performances included timed-peg placement and finger tapping, grip and pinch strength, walking 8 ft and turning 360° twice, and sensor-derived metrics assessing tandem walk. Multivariate linear regression models were used to examine the association of arteriolosclerosis across varied motor performances.

The participants (n=403) were on average 91.4 (6.1) years old at death, and 73.2% (n=295) were women. The frequency of moderate/severe arteriolosclerosis varied outside the cerebrum, ranging from 15.5% (40/258) in the pons to 49.6% (200/403) in the spinal cord. The correlation of the severity of arteriolosclerosis between these regions ranged from unrelated to modestly related. Spinal arteriolosclerosis was associated with impaired motor function (P=0.006), in particular more severe parkinsonism (estimate, 0.170; SE, 0.071; P=0.018) and less hand dexterity (estimate, -0.022; SE, 0.009; P=0.014). Arteriolosclerosis of the cerebellum was associated with impaired tandem walk (P=0.012), in particular more variability in the acceleration signal in the mediolateral direction (estimate, 0.023; SE, 0.011; P=0.040). Arteriolosclerosis in the pons or midbrain was not associated with motor performances.

Arteriolosclerosis severity varies in the central nervous system tissues outside of the cerebrum and is differentially associated with varied motor performances, suggesting that the adverse motor consequences of small vessel disease in older adults may be underestimated by studies focusing only on the brain.