Episodic memory deficit in HIV infection: common phenotype with Parkinson's disease, different neural substrates

Abstract

Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson's disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may also contribute. Here, the California Verbal Learning Test-II, administered to 42 PLWH, 41 PD participants, and 37 controls, assessed learning and retrieval using measures of free recall, cued recall, and recognition. Executive function was assessed with a composite score comprising Stroop Color-Word Reading and Backward Digit Spans. Neurostructural correlates were examined with MRI of frontal (precentral, superior, orbital, middle, inferior, supplemental motor, medial) and limbic (hippocampus, thalamus) volumes. HIV and PD groups were impaired relative to controls on learning and free and cued recall trials but did not differ on recognition or retention of learned material. In no case did executive functioning solely account for the observed mnemonic deficits or brain-performance relations. Critically, the shared learning and retrieval deficits in HIV and PD were related to different substrates of frontolimbic mnemonic neurocircuitry. Specifically, diminished learning and poorer free and cued recall were related to smaller orbitofrontal volume in PLWH but not PD, whereas diminished learning in PD but not PLWH was related to smaller frontal superior volume. In PD, poorer recognition correlated with smaller thalamic volume and poorer retention to hippocampal volume. Although memory deficits were similar, the neural correlates in HIV and PD suggest different pathogenic mechanisms.

Keywords: Episodic memory processes; HIV infection; Parkinson’s disease; Regional brain volume.

Fig. 1

Color-coded atlas identifying the regional volumes of the frontal cortices, hippocampus, and thalamus

Fig. 2

Graph depicting Z-scores over learning trials 1–5 in the HIV, PD, and CTRL groups

Fig. 3

Scatterplots depicting the double dissociation observed between frontal volumes and number of words recalled over learning trials 1–5: frontal orbital volume was related to learning over trials in the HIV group, whereas frontal superior volume was related to learning over trials in the PD group

Fig. 4

Scatterplots depicting the relationship between orbitofrontal volume and free and cued recall in the HIV and PD groups

Fig. 5

Scatterplots depicting the relationship between thalamic volume and recognition memory score in the HIV and PD groups. Note: there were 2 HIV participants who had outlying scores and were excluded from the scatterplot. Analyses with and without these HIV individuals resulted in similar Spearman’s rho and p values: HIV (n = 42) rho = − 0.226, p = 0.150; HIV (n = 40) rho = − 0.240, p = 0.135

Fig. 6

Scatterplots depicting the relationship between hippocampal volume and retention—free recall score in the HIV and PD groups