The prevalence of mild to moderate cognitive impairment, including episodic memory deficits, in people living with HIV (PLWH) remains high despite the life-extending success of antiretroviral pharmacotherapy. With PLWH now reaching near-normal life expectancy, questions concerning a potential synergy between age- and HIV disease-related effects, including degradation in fronto-limbic circuits, neural systems also compromised in Parkinson’s disease (PD), have emerged.

This cross-sectional study examined the similarities and differences in component processes of verbal episodic memory and their neural correlates in 42 PLWH, 41 individuals with PD, and 37 controls (CTRL) (all participants aged 45-79 years). Learning over five trials, short-delay (SD) and long-delay, (LD), free-recall (FR) and cued-recall (CR) indices were assessed using the California Verbal Learning Test-2. Retention scores for FR and CR were derived adjusting for Trial 5 performance. All memory scores were age- and education-corrected based on the control group and reported as Z-scores. Regional brain volumes were calculated using 3T MRI data and the SRI24 atlas to delineate frontal (precentral, superior, orbital, middle, inferior, supplemental motor, and medial) and limbic (hippocampus, thalamus) regions. Brain volumes were age- and head-sized corrected based on 238 controls (19-86 years old).

Compared with the CTRL group, the HIV and PD groups were impaired on learning across trials and on SD and LD free- and cued-recall, with no group difference between the HIV and PD groups on any score. All three groups benefited similarly from cues compared with free-recall. The HIV and PD groups did not differ from CTRL on retention scores. Regarding brain volumes, the HIV group had smaller middle frontal volumes than the PD or CTRL groups and smaller thalamic volumes than the PD group. Correlational analyses (Bonferroni correction for 8 comparisons, p<.01) indicated that fewer total number of words recalled on Trial 5, learning over Trials 1-5, total words recalled on SD-CR, LD-FR, and LD-CR were associated with smaller orbitofrontal volume in the HIV but not the PD group; the correlations between orbitofrontal volume and memory scores were significantly different between the HIV and PD groups. In PD, but not HIV, lower retention scores on SD-FR and LD-CR correlated to smaller hippocampal volume.

Impairment in learning and cued recall performance indicate that both encoding and retrieval processes are affected in PLWH and PD. Neural correlates of verbal memory differed between groups, with orbitofrontal volume associated with learning and recall in PLWH, whereas hippocampal volume was associated with retention scores in PD. Together, these results suggest that different nodes within the fronto-limbic mnemonic circuitry underlie the mutual verbal episodic memory deficits observed in older PLWH and PD. Support: AA023165, AA005965, AA107347, AA010723, NS07097, MH113406, and the Michael J. Fox Foundation for Parkinson’s Research

Preclinical Alzheimer disease (AD) has been associated with subtle deficits in memory, attention, and spatial navigation (Allison et al., 2019; Aschenbrenner et al., 2015; Hedden et al., 2013). There is a need for a widely distributable screening measure for detecting preclinical AD. The goal of this study was to examine whether self- and informant-reported change in the relevant cognitive domains, measured by the Everyday Cognition Scale (ECog; Farias et al., 2008), could represent robust clinical tools sensitive to preclinical AD.

Clinically normal adults aged 56-93 (n=371) and their informants (n=366) completed memory, divided attention, and visuospatial abilities (which assesses spatial navigation) subsections of the ECog. Reliability and validity of these subsections were examined using Cronbach’s alpha and confirmatory factor analyses (CFA). The hypothesized CFA assumed a three-factor structure with each subsection representing a separate latent construct. Receiver operating characteristics (ROC) and area under the curve (AUC) analyses were used to determine the diagnostic accuracy of the ECog subsections in detecting preclinical AD, either defined by cerebrospinal fluid (CSF) ptau181/Aß42 ratio >0.0198 or hippocampal volume in the bottom tertial of the sample. Hierarchical linear regression was used to examine whether ECog subsections predicted continuous AD biomarker burden when controlling for depressive symptomatology, which has been previously associated with subjective cognition (Zlatar et al., 2018). Lastly, we compared the diagnostic accuracy of ECog subsections and neuropsychological composites assessing the same or similar cognitive domains (memory, executive function, and visuospatial ability) in identifying preclinical AD.

All self- and informant-reported subsections demonstrated appropriate reliability (a range=.71-.89). The three-factor CFA models were an adequate fit to the data and were significantly better than one-factor models (self-report x2(3)=129.511, p<.001; informant-report X2(3)=145.347, p<.001), suggesting that the subsections measured distinct constructs. Self-reported memory (AUC=.582, p=.007) and attention (AUC=.564, p=.036) were significant predictors of preclinical AD defined by CSF ptau181/Aß42 ratio. Self-reported spatial navigation (AUC=.592, p=.022) was a significant predictor of preclinical AD defined by hippocampal volume. Additionally, self-reported attention was a significant predictor of the CSF ptau181/Aß42 ratio (p<.001) and self-reported memory was a significant predictor of hippocampal volume (p=.024) when controlling for depressive symptoms. Informant-reports were not significant predictors of preclinical AD (all ps>.074).

There was a nonsignificant trend for the objectively measured executive function AUC to be higher than for self-reported attention in detecting preclinical AD defined by CSF ptau181/Aß42 ratio and was significantly higher than self-reported attention in detecting preclinical AD defined by hippocampal volume (p=.084 and p<.001, respectively). For memory and spatial navigation/visuospatial domains, the AUCs for self-reported and objective measures did not differ in detecting preclinical AD defined by either CSF ptau181/Aß42 ratio or hippocampal volume (ps>.129).

Although the self-reported subsections produced significant AUCs, these were not high enough to indicate clinical utility based on existing recommendations (all AUCs<.60; Mandrekar, 2010). Nonetheless, there was evidence that self-reported cognitive change has promise as a screening tool for preclinical AD but there is a need to develop questionnaires with greater sensitivity to subtle cognitive change associated with preclinical AD.

Subtle changes in memory, attention, and spatial navigation abilities have been associated with preclinical Alzheimer disease (AD). The current study examined whether baseline AD biomarkers are associated with self- and informant-reported decline in memory, attention, and spatial navigation.

Clinically normal (Clinical Dementia Rating Scale (CDR®) = 0) adults aged 56–93 (N = 320) and their informants completed the memory, divided attention, and visuospatial abilities (which assesses spatial navigation) subsections of the Everyday Cognition Scale (ECog) annually for an average of 4 years. Biomarker data was collected within (±) 2 years of baseline (i.e., cerebrospinal fluid (CSF) p-tau181/Aβ42 ratio and hippocampal volume). Clinical progression was defined as CDR > 0 at time of final available ECog.

Self- and informant-reported memory, attention, and spatial navigation significantly declined over time (ps < .001). Baseline AD biomarkers were significantly associated with self- and informant-reported decline in cognitive ability (ps < .030), with the exception of p-tau181/Aβ42 ratio and self-reported attention (p = .364). Clinical progression did not significantly moderate the relationship between AD biomarkers and decline in self- or informant-reported cognitive ability (ps > .062). Post-hoc analyses indicated that biomarker burden was also associated with self- and informant-reported decline in total ECog (ps < .002), and again clinical progression did not significantly moderate these relationships (ps > .299).

AD biomarkers at baseline may indicate risk of decline in self- and informant-reported change in memory, attention, and spatial navigation ability. As such, subjectively reported decline in these domains may have clinical utility in tracking the subtle cognitive changes associated with the earliest stages of AD.

Preclinical Alzheimer disease (AD) has been associated with subtle changes in memory, attention, and spatial navigation abilities. The current study examined whether self- and informant-reported domain-specific cognitive changes are sensitive to AD-associated biomarkers.

Clinically normal adults aged 56–93 and their informants completed the memory, divided attention, and visuospatial abilities (which assesses spatial navigation) subsections of the Everyday Cognition Scale (ECog). Reliability and validity of these subsections were examined using Cronbach’s alpha and confirmatory factor analysis. Logistic regression was used to examine the ability of ECog subsections to predict AD-related biomarkers (cerebrospinal fluid (CSF) ptau181/Aβ42 ratio (N = 371) or hippocampal volume (N = 313)). Hierarchical logistic regression was used to examine whether the self-reported subsections continued to predict biomarkers when controlling for depressive symptomatology if available (N = 197). Additionally, logistic regression was used to examine the ability of neuropsychological composites assessing the same or similar cognitive domains as the subsections (memory, executive function, and visuospatial abilities) to predict biomarkers to allow for comparison of the predictive ability of subjective and objective measures.

All subsections demonstrated appropriate reliability and validity. Self-reported memory (with outliers removed) was the only significant predictor of AD biomarker positivity (i.e., CSF ptau181/Aβ42 ratio; p = .018) but was not significant when examined in the subsample with depressive symptomatology available (p = .517). Self-reported memory (with outliers removed) was a significant predictor of CSF ptau181/Aβ42 ratio biomarker positivity when the objective memory composite was included in the model.

ECog subsections were not robust predictors of AD biomarker positivity.