Date Published:
2023 Jul 01

Publication Type:
Journal Article

Authors:

J. Gonzalez
A. Wilson
D. Byrd
E.P. Cortes
J.F. Crary
S. Morgello

Secondary:
AIDS

Volume:
37

Pagination:
1247-1256

Issue:
8

PMID:
36988209

URL:
https://pubmed.ncbi.nlm.nih.gov/36988209

DOI:
10.1097/QAD.0000000000003556

Keywords:
Alzheimer Disease;Amyloid beta-Peptides;Cognitive Dysfunction;HIV Infections;Humans;Memory Disorders;Memory, Short-Term;Middle Aged;Positron-Emission Tomography;tau Proteins

Abstract:
<p>OBJECTIVES: As lifespans increase in people with HIV (PWH), there is concern that age-related neurodegenerative disorders may contribute to cognitive decline. We asked whether brain accumulation of Alzheimer's disease (AD)-associated proteins amyloid-beta (Aβ) and hyperphosphorylated tau (p-tau) predicted cognitive performance in middle-aged PWH.METHODS: In a prospectively followed, cognitively-characterized autopsy sample of 135 PWH, we used immunohistochemistry to assess Aβ plaques and neuronal p-tau in medial temporal and lateral frontal lobes. These pathologies were tested for associations with cognitive performance in seven domains: motor, speed of information processing, working memory, memory encoding, memory retrieval, verbal fluency, and abstraction/executive function. Univariate and multivariate analyses accounting for HIV-associated variables, reading level, and comorbidities were conducted. Longitudinal trajectories of memory functions were evaluated in 60 individuals with a median follow-up of 6.0 years.RESULTS: In this population with mean age 51.4 ± 0.9 years, 58% displayed neuronal p-tau and 29% Aβ plaques. Neuronal p-tau, but not Aβ, predicted worse memory encoding and retrieval, but not other cognitive functions. With an ordinal hierarchy of neuronal p-tau locations (entorhinal, hippocampal, neocortical), decreased memory performance correlated with neocortical distribution. Memory function trajectories could not be distinguished between individuals with and without neuronal p-tau, and over 80% of the sample showed no change over time.CONCLUSION: In this middle-aged sample, neuronal p-tau accumulation contributes to memory deficits, but is not associated with accelerated decline in function over time. In the absence of AD-like deterioration, other etiologies for neuronal p-tau in cognitively impaired PWH must be considered.</p>