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. 2025 Aug;29(8):2509-2518.
doi: 10.1007/s10461-025-04711-0. Epub 2025 Apr 28.

Diagnosis of Learning Disabilities but not Academic Difficulties Alone is Associated with Neurocognitive Impairment in People Living with HIV: Evidence from Clinical Research to Support and Refine the Current HAND Diagnostic Guidelines

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Diagnosis of Learning Disabilities but not Academic Difficulties Alone is Associated with Neurocognitive Impairment in People Living with HIV: Evidence from Clinical Research to Support and Refine the Current HAND Diagnostic Guidelines

Aneeka Ratnayake et al. AIDS Behav. 2025 Aug.

Abstract

Diagnosing HIV-associated neurocognitive disorder (HAND) is a complex process aimed at determining the role of HIV versus other causes of neurocognitive impairment. In treated people with living long-term HIV infection, this process is further complicated by the presence of multiple medical and psychiatric comorbidities and varied educational history. Evidence-based research is therefore needed to refine the 2007 HAND diagnostic criteria on how to consider multimorbidity in making differential diagnoses. This is the case for presence of academic difficulties versus diagnosis of learning disabilities (LD), which have not been systematically studied in relation to HAND, and especially in relation to the presence of cognitive and depressive symptoms. The current study included 903 people with HIV referred for a comprehensive neuropsychological assessment of HAND at the Neurobehavioural Clinical-Research Unit (St. Michael's Hospital in Toronto, ON, Canada). Pre-morbid ability was assessed prior to standard testing and participants were classified into LD groups: No learning disabilities (n = 474), academic difficulties (n = 352) or diagnosed learning disability (LD, n = 77). The neuropsychological test battery assessed domains of complex attention, learning and memory, psychomotor efficiency, and executive functioning, and performance was adjusted with demographic corrections. Neurocognitive impairment (NCI) status was determined using the global deficit score method (GDS ≥ 0.5 detecting at least mild global NCI). Depressive symptoms were assessed with the Beck Depression Inventory (BDI), and cognitive symptoms with the Patient's Assessment of Own Functioning (PAOFI). Logistic regression models were used to assess odds of NCI in the three groups while considering main and interactive effects of clinically relevant depression (BDI > 10) or elevated cognitive symptoms (PAOFI > 3). Only LD diagnosis was significantly associated with increased odds of NCI, OR = 1.90, 95% CI (1.15, 3.14). In the same model, both cognitive symptoms, OR = 1.97, 95% CI (1.50, 2.58), and depression symptoms OR = 1.39, 95% CI (1.06, 1.82) were also significantly associated with increased odds of NCI, but not their interaction. Diagnosis of LD, but not academic difficulties alone, is associated with increased odds of NCI among treated persons living with HIV who are clinically referred. While this was in part independent of depression and cognitive symptoms, adults with HIV and LD diagnosis who had high depression and cognitive symptoms had greatest odds of NCI. These findings assist in the refinement of the current HAND diagnostic guidelines.

Keywords: Cognitive symptoms; Depression; HIV-associated neurocognitive disorder; Learning disabilities.

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Conflict of interest statement

Declarations. Competing Interests: The authors have no competing interests to declare. Ethical Approval: This study was reviewed and approved by Unity Health Toronto.

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