No abstract

Clinicopathologic data from 285 autopsies were analyzed. The decedents were long-standing participants in the Honolulu-Asia Aging Study, a prospective epidemiologic investigation of stroke, neurodegenerative diseases, and aging. We assessed the prevalence at death of four primary neuropathologic processes using specific microscopic lesions as indicators. An algorithm was developed to assign each decedent to one of six subsets, corresponding to pathologic dominance by microvascular lesions (14% of decedents), Alzheimer lesions (12%), hippocampal sclerosis (5%), cortical Lewy bodies (5%), codominance by two or more primary processes (9%), or without a dominant pathologic process recognized (55%). Definite or probable dementia had been identified in 118 of the decedents. The proportions of men in each subset identified as demented were (in the same order) 57%, 53%, 79%, 57%, 76%, and 25%. In this autopsied panel of older Japanese-American men, the importance of microvascular lesions as a likely explanation for dementia was nearly equal to that of Alzheimer lesions. The cerebrovascular lesion type most essentially and inclusively related to dementia was multiple microinfarction.

Two women (26 and 40 years old) developed an unusual microangiopathy that affected the brain and retina. Psychiatric symptoms initially overshadowed the subacute features of the progressive neurologic disorder. Ophthalmoscopic findings of multifocal branch retinal artery occlusions provided clinical evidence of vasculopathy. Laboratory data did not reveal evidence of the known vasculitides, including systemic lupus erythematosus (SLE) and syphilis. Cerebral angiography suggested vasculitis in the younger patient. Brain biopsy in the older patient (after 3 months of steroid therapy) revealed a sclerosis of the small pial and cortical vessels that was consistent with a "healed" angitis. Both patients seemed to respond to steroid therapy.

Substantia nigra (SN) neurons were counted on single, transverse caudal midbrain sections from 217 male participants in the Honolulu-Asia Aging Study, aged 74-97 years at death. Quadrants areas within the SN were determined with a planimeter and neuronal density was expressed as neurons/mm(2) for 10 Parkinson's disease (PD) cases, 29 incidental Lewy body cases, and 178 controls with neither condition. Mean densities in all quadrants were significantly lower in the PD group compared with the other groups (p = 0.006). This relationship was strongest in the ventrolateral quadrant. In a subgroup of 50 controls who were examined with the Unified Parkinson's Disease Rating Scale an average of 2.1 years prior to death, there was an association of stooped posture (p = 0.009), postural instability (p = 0.013), body bradykinesia (p = 0.048), and gait disturbance (p = 0.05) with neuron density in the dorsolateral quadrant; and impaired speech (p = 0.014), abnormal facial expression (p = 0.022), and difficulty rising from a chair (p = 0.032) with neuron density in the dorsomedial quadrant. There was a significant association of increasing number of signs present with decreasing neuron density in both quadrants (p = 0.001 for trend). Low SN neuron density may be the basis for parkinsonian signs in the elderly without PD.

Concomitant cerebrovascular (CV) lesions increase risk 1 and severity 2 of clinical dementia in patients meeting neuropathological criteria for Alzheimer's disease (AD).1,2 Japanese-American men participating in the Honolulu-Asia Aging Study (HAAS) had less frequent and lower densities of neuritic plaques (NPs) than similarly aged white men.3 Even among decedents in this cohort with moderate to severe dementia, NP densities were less than reported for white male dementia subjects. Whether coexistent CV lesions increase the likelihood of clinical dementia in individuals with sparse NP and neurofibrillary tangles (NFTs) is unknown.The postmortem series of the HAAS offers an ideal opportunity to study the possibility that decedents with negligible densities of NP and NFT could be at increased risk for crossing the threshold to clinical dementia if they have coexistent CV lesions. This report evaluates the presence (alone and in various combinations) of NP, NFT, and CV lesions in brains of cognitively normal, marginal, and demented decedent Japanese-American men.