Mixed pathology is more likely in black than white decedents with Alzheimer dementia

Abstract

Objective: To compare the burden of neuropathology in black and white participants with clinical Alzheimer disease (AD). Methods: Participants included 122 persons enrolled in the Rush Alzheimer's Disease ClinicalCore, a prospective cohort study of AD. Forty-one black decedents were matched two-to-one to 81 white decedents according to age at death, sex, years of education, and cognition proximate to death. We examined common brain pathologies related to dementia (AD, Lewy body, and macroscopic and microinfarct pathology) and arteriolar sclerosis and atherosclerosis. We calculated the frequency of each dementia pathology both alone and in combination (mixed pathologies). Racial differences in the odds of a single pathology vs mixed pathologies, and in the odds of vessel disease and its severity, were examined using logistic regression analyses.Results: AD pathology was confirmed in .93% of both black and white decedents with AD dementia. However, black decedents were less likely to have Alzheimer pathology as a single dementia pathology than white decedents (19.5% vs 42.0%), and were more likely to have AD mixed with an additional pathology (70.7% vs 50.6%), particularly Alzheimer pathology and Lewy bodies, and Alzheimer pathology, Lewy bodies, and infarcts. Black decedents also had more severe arteriolar sclerosis and atherosclerosis. Alzheimer disease (AD) dementia, a devastating and common neurodegenerative disease, is a leading cause of disability in our aging society. It is increasingly recognized that the underlying pathologic basis of AD dementia is heterogeneous and frequently mixed. Many cases of AD dementia demonstrate an underlying AD pathology, yet other dementia-related pathologies including Lewy bodies and infarcts frequently coexist with AD pathology and add to the likelihood of clinically symptomatic AD. 1,2Knowledge about the neuropathologic basis of AD dementia has been based almost exclusively on autopsy studies of white persons. There is a dearth of neuropathologic information available in older black persons with AD dementia despite the fact that they may have a higher prevalence and incidence of AD dementia than white persons, 3,4 as well as a disproportionate burden of vascular disease. 5,6 In the current study, we tested the hypothesis that mixed pathologies, in particular AD pathology and infarcts, are more common in black than white participants with AD dementia.METHODS Participants. Participants included 122 deceased persons with AD dementia from the Rush Alzheimer's Disease Clinical Core 7 : 41 consecutive autopsied black decedents matched to 81 white decedents. All participants were evaluated for possible dementia at either the Rush Memory Clinic or a neighboring memory assessment clinic at a county hospital in the Illinois Medical

Cerebral Amyloid Angiopathy: Similarity in African-Americans and Caucasians with Alzheimer’s Disease

“…In our primary cohort of 37 subjects, the prevalence of comorbidities was slightly higher among African-Americans (30 comorbidities in 18 subjects) compared to Caucasians (25 comorbidities in 19 subjects). In particular, African-Americans tended to have more α-synucleinopathy than did Caucasians, consistent with previous investigations[7, 20]. Several systemic risk factors for age-associated cognitive decline also are more prevalent among African-Americans, such as cardiovascular and metabolic disorders[17, 18], including hypertension[19]; as expected, more African-American subjects in both the Emory and NACC cohorts had been diagnosed with hypertension than had Caucasians, although both groups had similar levels of CAA.…”

“…Older AD patients in general are more likely than younger patients to manifest comorbid brain disorders such as α-synucleinopathy and microinfarcts[7, 58], and such mixed brain pathologies have been reported to be more common in blacks than whites with clinical AD[20]. In our primary cohort of 37 subjects, the prevalence of comorbidities was slightly higher among African-Americans (30 comorbidities in 18 subjects) compared to Caucasians (25 comorbidities in 19 subjects).…”

“…Aging African-Americans are at a relatively high risk of developing cardiovascular and metabolic disorders[17–19] as well as mixed pathologies in the brain, particularly plaques and tangles along with α-synucleinopathy (Lewy body disease) and/or infarcts[7, 20]. The contribution of cardiovascular disease to dementia has received special attention because African-Americans are especially susceptible to hypertension[19], diabetes/metabolic disorder[1, 5, 21, 22], cerebrovascular disease[7] and stroke[23–25].…”

The ARIC-PET amyloid imaging study

“…7,8 Thus, a larger component of dementia in blacks may be due to vascular disease, supported by recent data showing that black decedents with clinical AD more frequently have mixed pathologies on autopsy, 9 or that some autopsy series select racial groups differentially. Further, typical AD risk factors may have different associations with clinical AD in blacks than in whites.…”

A clinicopathological approach to the diagnosis of dementia

“…Most patients with DLB show mixed pathology, with concomitant presence of vascular disease and/or AD pathology 184–186 . Similarly, the cortical pathology observed in patients with PDD is often mixed 187,188 , with coexisting AD pathology leading to more-advanced dementia 189 .…”