Background: Both family history of dementia (FHD) and lower levels of
Aβ-42 are indepentently associated with worse neurocognitive functioning in HIVinfected
Objective: To examine the relationships between cerebrospinal fluid (CSF) Aβ-42 and FHD with HIV-associated
neurocognitive disorders (HAND).
Methods: One hundred eighty-three HIV+ adults underwent neuropsychological and neuromedical assessments, and
determination of CSF Aβ-42 concentration and FHD (defined as a self-reported first or second-degree relative with a
dementia diagnosis). Univariate analyses and multivariable logistic regressions were used.
Results: FHD was not associated with HAND (p = 0.24); however, CSF Aβ-42 levels were lower (p = 0.03) in the HAND
group, but were not associated with FHD (p = 0.89). Multivariable models showed a main effect of CSF Aβ-42 (p = 0.03)
and a trend-level (p = 0.06) interaction between FHD and CSF Aβ-42, such that lower CSF Aβ-42 was associated with
HAND in those with FHD (p < 0.01) compared to those without FHD (p = 0.83). An analysis in those with follow-up data
showed that higher baseline CSF Aβ-42 was associated with lower risk of neurocognitive decline (p = 0.02). While we did
not find an FHD X CSF Aβ-42 interaction (p = 0.83), when analyses were stratified by FHD, lower CSF Aβ-42 was associated at
the trend-level with neurocognitive decline in the FHD group (p = 0.08) compared to the no FHD group (p = 0.15).
Conclusion: FHD moderates the relationship between of CSF Aβ-42 and HAND. The findings highlight the complexities
in interpreting the relationships between biomarkers of age-related neurodegeneration and HAND.