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Alzheimer's disease neuropathology may not predict functional impairment in HIV: a report of two individuals.

ABSTRACT: With aging of HIV populations, there is concern that Alzheimer's disease (AD) may become prevalent and difficult to distinguish from HIV-associated neurocognitive disorders. To date, there are no reports documenting histologically verified Alzheimer's neuropathology in individuals with HIV and dementia. Herein, we report two antiretroviral-treated, virally suppressed, HIV-infected individuals autopsied by the Manhattan HIV Brain Bank. Subject A presented to study at 52 years, already dependent in instrumental activities of daily living (ADLs), with severe cognitive impairment inclusive of learning and memory dysfunction. Her history was significant for educational disability and head trauma. She had rapid cognitive decline and, by death at age 59 years, was bed-bound, incontinent, and non-communicative. At autopsy, she exhibited severe AD neuropathologic change (NIA-AA score A3B3C3) and age-related tau astrogliopathy (ARTAG). She was homozygous for APOE ?3/?3. No HIV DNA was detected in frontal lobe by nested polymerase chain reaction. Subject B was a community dwelling 81-year-old woman who experienced sudden death by pulmonary embolus. Prior to death, she was fully functional, living independently, and managing all ADLs. At autopsy, she displayed moderate amyloid and severe tau AD neuropathologic changes (A2B3C2), ARTAG, and cerebral congophilic angiopathy. She was an APOE ?3/?4 heterozygote, and HIV DNA, but not RNA, was detected in frontal lobe, despite 20 years of therapy-induced viral suppression. We conclude that in the setting of HIV, AD neuropathology may occur with or without symptomatic cognitive dysfunction; as with seronegative individuals, there are likely to be complex factors in the generation of clinically relevant impairments.

SUBMITTER: Morgello S

PROVIDER: S-EPMC6202220 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Alzheimer's disease neuropathology may not predict functional impairment in HIV: a report of two individuals.

Morgello Susan S Jacobs Michelle M Murray Jacinta J Byrd Desiree D Neibart Eric E Mintz Letty L Meloni Gregory G Chon Christina C Crary John J

Journal of neurovirology 20180809 5

With aging of HIV populations, there is concern that Alzheimer's disease (AD) may become prevalent and difficult to distinguish from HIV-associated neurocognitive disorders. To date, there are no reports documenting histologically verified Alzheimer's neuropathology in individuals with HIV and dementia. Herein, we report two antiretroviral-treated, virally suppressed, HIV-infected individuals autopsied by the Manhattan HIV Brain Bank. Subject A presented to study at 52 years, already dependent i ...[more]

PMID: 30094630

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Project description:BackgroundApolipoprotein E epsilon 4 (APOE-ε4) carrier status is an established risk factor for Alzheimer's disease (AD) dementia. It has also been linked with sleep disturbance in healthy older adults and increased insomnia risk. This association may be driven by the effect of APOE-ε4 on AD pathological change, itself associated with sleep abnormalities. To assess this relationship, we have evaluated post-mortem neuropathological findings in patients with and without cognitive impairment and AD pathology, who had extensive clinical assessment within 12 months of death.MethodsThis retrospective cohort study used UK Brain Banks Network data. Eligible subjects were aged over 50, with pre-mortem neuropsychiatry inventory scores of sleep disturbance (NPI-K), neurocognitive testing and functional cognitive status assessment (Clinical Dementia Rating scale). Neuropathological data included Thal phase, Braak stage and CERAD scores (measures of Aβ plaque distribution, tangle distribution and neuritic plaque density, respectively) combined to form the National Institute on Aging Alzheimer's Association (NIA-AA) ABC score reflecting AD neuropathology. Participants with other significant intracerebral pathology or pathological features of non-AD dementia were excluded. Multivariate linear regression was performed with NPIK Global Score (NPIK frequency score multiplied by severity score) as the dependent variable and APOE-ε4 heterozygosity or homozygosity as independent variables. Covariates included age, gender, APOE-ε2 status and ABC NPI measures reflecting depression and anxiety. Further models stratified by ABC score and functional cognitive status were also produced.ResultsSeven hundred twenty-eight records were identified. Two hundred two participants were included in the final analysis: mean (SD) age 84.0 (9.2) and MMSE 14.0 (11.8). Mean sleep disturbance scores were highest in ε4 homozygosity (n=11), 4.55 (5.4); intermediate in ε4 heterozygosity (n=95), 2.03 (4.0); and lowest in non-ε4 carriers (n=96), 1.36 (3.3). Within the full sample, controlling for pathological status, age, gender, depression, anxiety and CDR-SOB status, APOE-ε4 homozygosity was associated with sleep disturbance (β 2.53, p=0.034). APOE-ε4 heterozygosity was similarly associated in individuals without dementia (β 1.21, p=0.048).ConclusionThese findings lend weight to the hypothesis that APOE-ε4 affects sleep by mechanisms independent of AD pathological change. Evaluation of those mechanisms would enhance understanding of sleep disturbance pathways and potentially provide treatment targets.

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Alzheimer's disease neuropathology may not predict functional impairment in HIV: a report of two individuals.

Publications

Alzheimer's disease neuropathology may not predict functional impairment in HIV: a report of two individuals.

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