BRAINSTEM NEURONAL LOSS OCCURRING INDEPENDENTLY FROM NEOCORTICAL ALZHEIMER, LEWY BODY, OR FOCAL ISCHEMIC LESIONS IS COMMON AND SIGNIFICANTLY ASSOCIATED WITH BOTH MOTOR AND COGNITIVE IMPAIRMENT IN AUTOPSIED HONOLULU-ASIA AGING STUDY DECEDENTS

Abstract

The neuropathologic abnormalities to which aging-related cognitive impairment is commonly attributed include neocortical neurofibrillary tangles, neuritic amyloid plaques, cortical Lewy bodies, hippocampal sclerosis, and vascular brain injury with microinfarcts and/or lacunar infarcts. Motor impairments are very common with aging and occur often but not invariably with dementia. The brain abnormalities generally recognized as common and relevant to motor impairments are infarcts, hemorrhage, and Lewy bodies in the substantia nigra, Repeated cognitive and motor function assessments were carried out over two decades on Japanese-American male Honolulu-Asia Aging Study participants. This analysis was carried out on 774 HAAS decedents who received comprehensive, highly standardized brain autopsies at death. Cognitive assessments utilized the Cognitive Assessment and Screening Instrument. Grip strength, walking speed, stride length, turn around steps, turn around time, chair stands, and standing balance were assessed on 6 occasions. Analyses utilized graphic and tabular visual representation plus linear and logistic regression statistical modeling. Decedents with cognitive impairment but little or no motor impairment were found at autopsy to have neocortical neurofibrillary tangles and amyloid plaques, microinfarcts and/or lacunar infarcts, and hippocampal sclerosis, but negligible striatal, cerebellar, or brainstem abnormalities. Those who had both cognitive and motor impairments had these same lesions plus neocortical Lewy bodies, generalized brain atrophy, and striatal and brainstem neuronal loss and gliosis. In a subset of autopsied cases without neocortical Alzheimer lesions, Lewy bodies (brainstem or neocortex), microinfarcts, or hippocampal sclerosis, neuronal loss and gliosis observed in the brainstem was nonetheless significantly associated with both cognitive and motor impairments. These findings suggest that linked cognitive and motor impairments may be associated with brainstem neuronal injury due in part to currently undefined disease processes distinct from other neuropathologic processes represented by neocortical Alzheimer lesions, Lewy bodies, vascular brain injury, and/or hippocampal sclerosis.