Neuropsychological Tests Of Memory Research Articles

Increasing hexokinase 1 expression improves mitochondrial and glycolytic functional deficits seen in sporadic Alzheimer's disease astrocytes.

Abnormalities in cellular metabolism are seen early in Alzheimer's disease (AD). Astrocyte support for neuronal function has a high metabolic demand, and astrocyte glucose metabolism plays a key role in encoding memory. This indicates that astrocyte metabolic dysfunction might be an early event in the development of AD. In this paper we interrogate glycolytic and mitochondrial functional changes and mitochondrial structural alterations in patients' astrocytes derived with a highly efficient direct conversion protocol. In astrocytes derived from patients with sporadic (sAD) and familial AD (fAD) we identified reductions in extracellular lactate, total cellular ATP and an increase in mitochondrial reactive oxygen species. sAD and fAD astrocytes displayed significant reductions in mitochondrial spare respiratory capacity, have altered mitochondrial membrane potential and a stressed mitochondrial network. A reduction in glycolytic reserve and glycolytic capacity is seen. Interestingly, glycolytic reserve, mitochondrial spare respiratory capacity and extracellular lactate levels correlated positively with neuropsychological tests of episodic memory affected early in AD. We identified a deficit in the glycolytic enzyme hexokinase 1 (HK1), and correcting this deficit improved the metabolic phenotype in sAD not fAD astrocytes. Importantly, the amount of HK1 at the mitochondria was shown to be reduced in sAD astrocytes, and not in fAD astrocytes. Overexpression of HK1 in sAD astrocytes increases mitochondrial HK1 levels. In fAD astrocytes HK1 levels were unaltered at the mitochondria after overexpression. This study highlights a clear metabolic deficit in AD patient-derived astrocytes and indicates how HK1, with its roles in both oxidative phosphorylation and glycolysis, contributes to this.

Cognitive Performance Between Latino and White Non-Latino Individuals With Parkinson's Disease.

Cognitive impairment is a common nonmotor symptom in Parkinson's disease (PD). Individuals of Latino background are traditionally underrepresented in research on PD. Despite the fact that Latinos comprise 18% of the U.S. population, they commonly make up less than 5% of samples in studies of PD. Emerging evidence suggests that Latino individuals with PD may experience disparities relative to White non-Latinos in terms of having more severe motor symptoms, more severe depressive symptoms, and worse health-related quality of life. The purpose of the present study was to investigate differences in cognitive performance between Latino and White non-Latino individuals with PD and examine correlates of cognitive performance. Data were obtained from the Parkinson's Progression Markers Initiative. Participants included 60 Latino individuals with PD and 1,009 White non-Latino individuals with PD, all of whom were followed annually for up to 5 years. Participants completed neuropsychological tests of attention and working memory, processing speed, visuospatial functioning, verbal fluency, and immediate and delayed memory and recall. Relative to White non-Latino individuals with PD, Latino individuals with PD had significantly lower scores on the global measure of cognitive functioning, a test of processing speed, and tests of working memory and attention. Years of education was the strongest correlate of performance in these three cognitive domains among individuals in the Latino group. These findings provide initial evidence of disparities in cognitive functioning among Latino individuals with PD. Educational disadvantages may be one potential driver of these disparities.

The processing of verbal memories after traumatic brain injury

Objective: Memory dysfunction is a persistent cognitive symptom following traumatic brain injury (TBI), negatively impacting capacity for independent living and productivity. Traditional scoring of neuropsychological memory tests does not allow for differentiation of specific impairments of encoding, consolidation and/or retrieval, or the potential impact of strategy deficits. Method: The current study examined performance of 142 moderate-to-severe TBI participants and 68 demographically matched healthy controls on the Rey Auditory Verbal Learning Test (RAVLT) using Item Specific Data Analysis (ISDA) and strategy use analyses. Results: Results revealed significantly greater impairments in encoding, consolidation, and retrieval in TBI participants, compared to controls. Encoding deficits significantly explained the most variance in the long-delayed recall of TBI participants, followed by consolidation, and then retrieval. Participants with TBI showed a reduced ability to spontaneously apply strategies during learning, evident in decreased subjective clusters and increased word omissions, compared to controls. No difference was found between groups in passive learning strategy application, shown through serial clustering. Spontaneous strategy measures both uniquely accounted for variance in the encoding ability of TBI participants. Conclusions: These findings highlight the potential value in using ISDA and strategy use measures to assess RAVLT results to better characterize individual memory profiles and inform rehabilitative interventions.

Apathy and Depression Among People Aging With Traumatic Brain Injury: Relationships to Cognitive Performance and Psychosocial Functioning.

Apathy and depression are both common after moderate to severe traumatic brain injury (TBI) and may be especially important to distinguish in older adults with TBI. The authors examined apathy and depression in relation to cognitive performance domains and their potentially unique contribution to psychosocial functioning in this patient population. A total of 106 participants (mean±SD age=64±8 years) with chronic moderate to severe TBI (≥1 year) completed questionnaires assessing severity of apathy (Frontal Systems Behavior Scale-apathy subscale) and depression (Geriatric Depression Scale-15) symptoms, health-related quality of life (HRQoL), and societal participation. Participants also completed neuropsychological tests of episodic memory, processing speed, and executive functioning. Apathy symptom severity was significantly associated with all cognitive performances in correlations adjusted for the familywise error rate; a relationship with executive functioning remained after controlling for demographic and injury variables. Depression symptom severity was not significantly associated with cognition after statistical correction. Both symptomatologies uniquely contributed to HRQoL. Only depression symptoms contributed to societal participation. On the basis of clinical cutoffs, half the sample had neither depression nor apathy, approximately 25% met criteria for only apathy, and 25% had both apathy and depression. The combined presence of clinical depression and apathy was associated with worse HRQoL and societal participation. This is the first study to examine apathy and depression in relation to cognition and psychosocial functioning in an older sample with a history of TBI. Findings suggest that the two syndromes can be dissociated in clinically meaningful ways, which may help to refine psychiatric and behavioral interventions in this vulnerable population.

24 Functional Distinctions in Metabolic Network Patterns in Parkinson's Disease

Objective:Cognitive decline is a common non-motor feature of Parkinson's disease (PD). However, the underlying mechanisms of cognitive impairment in PD require further elucidation. FDG PET imaging data analyses have revealed distinct brain metabolic patterns associated with the cognitive features of PD. The PD cognition-related pattern (PDCP) and default mode network (DMN) are two overlapping, but topographically distinct, networks that may serve as biomarkers of cognitive decline in PD. Decreased activity of the resting-state DMN and increased expression of the PDCP are associated with cognitive impairment in PD. Studies have consistently demonstrated the association between neuropsychological memory test performance and PDCP expression. Thus, we examined whether memory performance could offer additional value in predicting PDCP expression in PD patients. We hypothesized that DMN and memory performance would predict greater variance in PDCP expression than the DMN alone.Participants and Methods:Participants included 48 PD patients ages 46-80 (mean (SD) Age: 61.9 (8.1), Education: 15.0 (2.8), IQ: 112.5 (14.9), DRS total: 136.7 (5.8)). All participants completed the FDG PET and neuropsychological evaluation 8-12 hours after their last dose of Levodopa. Neuropsychological memory testing included the California Verbal Learning Test (CVLT) z score of sum of learning trials. PDCP and DMN values were z scores generated from normal controls in previous studies. Data were analyzed using linear regression analyses.Results:A hierarchical regression was performed to predict PDCP as a function of DMN and CVLT learning performance. Variables were entered in two separate blocks. The first block included DMN as a predictor, and the overall regression was significant (R2 = 0.55, F(1, 39)= 47.0, p < 0.001). As hypothesized, DMN significantly predicted PCDP expression (β= -0.74, p < 0.001). The second block of the regression included CVLT learning memory performance. Both DMN and CVLT performance explained a significant amount of variance in PDCP (R2 change = 0.05, F(2, 39)= 27.6, p < 0.001). CVLT performance significantly predicted PDCP (β= -0.22, p =0.048). The final model accounted for 60.0% of the variance in PDCP.Conclusions:Disruptions in functional connectivity within brain networks have become increasingly recognized as mechanisms responsible for cognitive impairment in patients. As demonstrated in previous studies, our results indicated that DMN loss is a strong predictor of PDCP expression, likely due to the networks' overlapping spatial regions. However, we found that the addition of memory performance to the model could explain a small amount of variance (5%) over and above DMN expression. Overall, the current findings demonstrate a functional (i.e., learning) distinction between population-specific (PDCP) and more general brain networks (DMN).

5 The Association of Neighborhood Socioeconomic Deprivation with Neurocognition in a Diverse Cohort of Middle- and Older-Aged Persons Living with and Without HIV

Objective:Due to decades of structural and institutional racism, minoritized individuals in the US are more likely to live in low socioeconomic neighborhoods, which may underlie the observed greater risk for neurocognitive impairment as they age. However, these relationships have not been examined among people aging with HIV. To investigate neurocognitive disparities among middle- and older-aged Latino and non-Latino White people living with HIV (PWH), and whether neighborhood socioeconomic deprivation may partially mediate these relationships.Participants and Methods:Participants were 372 adults ages 40-85 living in southern California, including 186 Latinos (94 PWH, 92 without HIV) and 186 non-Latino (NL) Whites (94 PWH, 92 without HIV) age-matched to the Latino group (for the overall cohort: Age M=57.0, SD=9.1, Education: M=12.7, SD=3.9, 38% female; for the group of PWH: 66% AIDS, 88% on antiretroviral therapy [ART]; 98% undetectable plasma RNA [among those on ART]). Participants completed psychiatric and neuromedical evaluations and neuropsychological tests of verbal fluency, learning and memory in person or remotely. Neuropsychological results were converted to demographically-unadjusted global scaled scores for our primary outcome. A neighborhood socioeconomic deprivation variable (SESDep) was generated for census tracts in San Diego County using American Community Survey 2013-2017 data. Principal components analysis was used to create one measure using nine variables comprising educational (% with high school diploma), occupational (% unemployed), economic (rent to income ratio, % in poverty, (% female-headed households with dependent children, % with no car, % on public assistance), and housing (% rented housing, % crowded rooms) factors. Census tract SESDep values were averaged for a 1km radius buffer around participants’ home addresses.Results:Univariable analyses (independent samples t-tests and Chi-square tests) indicated Latinos were more likely to be female and had fewer years of formal education than NL-Whites (ps<.05). Latino PWH had higher nadir CD4 than White PWH (p=.02). Separate multivariable regression models in the overall sample, controlling for demographics and HIV status, showed Latinos had significantly lower global scaled scores than Whites (b=-0.59; 95%CI-1.13, -0.06; p=.03) and lived in more deprived neighborhoods (b=0.62; 95%CI=0.36, 0.88; p<.001). More SES deprivation was significant associated with worse global neurocognition in an unadjusted linear regression (b=-0.55; 95%CI=-0.82, -0.28; p<.001), but similar analyses controlling for demographics and HIV status, showed SESDep was not significantly related to global scaled scores (b=-0.11; 95%CI= -0.36, 0.14; p=.40). Exploratory analyses examined primary language (i.e., English vs Spanish) as a marker of Hispanic heterogeneity and its association with neurocognition and SESDep. Controlling for demographics and HIV status, both English-speaking (b=0.33; 95%CI=0.01. 0.64; p=.04) and Spanish-speaking Latinos (b=0.88; 95%CI=0.58, 1.18; p<.001) lived in significantly greater SESDep neighborhoods than Whites, with SESDep greater for Spanish-speakers than English-speakers (p<.001). However, only English-speaking Latinos had significantly lower neurocognition than Whites (b=-0.91; 95%CI=0-1.57, -0.26; p<.01; Spanish-speakers: b=-0.27; 95%CI=-0.93, 0.38; p=.41).Conclusions:Among our sample of diverse older adults living with and without HIV, English-speaking Latinos showed worse neurocognition than Whites. Though SES neighborhood deprivation was worse among Latinos (particularly Spanish-speakers) it was not associated with neurocognitive scores after adjusting for demographics. Further studies investigating other neighborhood characteristics and more nuanced markers of Hispanic heterogeneity (e.g., acculturation) are warranted to understand factors underlying aging and HIV-related neurocognitive disparities among diverse older adults.

1 Network Efficiency as Structural Reserve: Pre- And Post-Operative Associations Between Network Organization and Memory in Temporal Lobe Epilepsy

Objective:Memory impairment is a common comorbidity in individuals with temporal lobe epilepsy (TLE). Further, in medication-resistant epilepsy the frontline option, neurosurgical epileptogenic zone destruction, places memory at significant risk. Research has highlighted that TLE causes whole-brain network efficiency disruption, but it is not established how this may explain pre- and post-surgical cognition. Here we examine whether white matter structural network organization predicts pre-operative memory function and/or risk for post-operative memory decline.Participants and Methods:Patients with drug-resistant TLE were recruited from two epilepsy centers in a prospective longitudinal study. The pre-operative sample included 51 individuals with left TLE (L-TLE), 52 with right TLE (R-TLE), and 57 healthy controls who underwent T1- and diffusion-weighted MRI (dMRI), and neuropsychological tests of verbal and visual memory. Forty-four patients (n=21 L-TLE) subsequently underwent temporal lobe surgery (36 anterior temporal lobectomy; 7 stereotactic laser amygdalohippocampectomy; 1 amygdalohippocampectomy) and completed post-operative memory testing. Whole-brain connectomes were generated via diffusion tractography and analyzed using graph theory, focusing on network integration (path length) and specialization (transitivity). In the preoperative dataset, first we compared TLE versus controls with analysis of covariance (ANCOVAs) controlling for age. Next, linear regressions examined the association between memory scores and network efficiency between L-TLE, R-TLE and controls. In the post-operative sample, bivariate correlations examined the association between pre- to post-operative memory change and 1) global network efficiency and 2) asymmetry of mesial temporal efficiency (i.e., local efficiency of the hippocampal, parahippocampal, and entorhinal nodes). Finally, efficiency metrics were entered into stepwise regressions along with established predictors of memory decline.Results:Compared to controls, TLE showed longer path length (p < .05; ηp2 = .03) and lower transitivity (p = .01; ηp2 = .04). Pre-operatively, better verbal learning and memory were associated with both shorter path length (β = -0.23 to -0.32; psadjusted < .05) and increased transitivity (β = 0.20 to 0.31; psadjusted < .05). These associations were greater in L-TLE than R-TLE (i.e., a significant interaction; β = -0.29 to 0.25; psadjusted <.05). Post-operatively, global metrics predicted decline on list learning for LTLEs (rs = -.57 to .58; ps < .01), and were marginal on list recall (rs = -.42 to .40; ps < .10). Leftward asymmetry of mesial temporal local efficiency predicted greater decline across most verbal memory measures for L-TLE (rs -.47 to -59; psadjusted <.05), but not R-TLE. Asymmetry of mesial network efficiency uniquely explained at least 20 to 43% of the variance in list learning, recall, and story learning for L-TLE, outperforming hippocampal asymmetry and preoperative score (psadjusted <.05).Conclusions:Our findings suggest that global white matter network abnormalities contribute to verbal memory impairment pre-operatively and vulnerability to decline post-operatively in L-TLE. Asymmetry of a predefined mesial temporal sub-network may help predict post-operative memory function following left temporal lobe surgery, such that greater efficiency in the to-beresected mesial temporal network may be an important risk factor for decline. Our findings extend the importance of network approaches in TLE to include the relationships between neurobiological networks and memory function.

52 Open Access, Normative Morphometric Software Indicate Neurodegeneration Associated with Episodic Memory Dysfunction in Amnestic MCI

Objective:Neurodegeneration in Alzheimer’s disease (AD) is typically assessed through brain MRI, and proprietary software can provide normative quantification of regional atrophy. However, proprietary software can be cost-prohibitive for research settings. Thus, we used the freely available software NOrmative Morphometry Image Statistics (NOMIS) which generates normative z-scores of segmented T1-weighted images from FreeSurfer to determine if these scores replicate established patterns of neurodegeneration in the context of amnestic mild cognitive impairment (aMCI), and whether these measures correlate with episodic memory test performance.Participants and Methods:Patients with aMCI (n = 25) and cognitively normal controls (CN; n = 74) completed brain MRI and two neuropsychological tests of episodic memory (the Rey Auditory Verbal Learning Test and the Wechsler Logical Memory Tests I & II), from which a single composite of normed scores was computed. A subset returned for follow-up (aMCI n = 11, CN n = 52) after ∼15 months and completed the same procedures. T1-weighted images were segmented using FreeSurfer v6.0 and the outputs were submitted to NOMIS to generate normative morphometric estimates for AD-relevant regions (i.e., hippocampus, parahippocampus, entorhinal cortex, amygdala) and control regions (i.e., cuneus, lingual gyrus, pericalcarine gyrus), controlling for age, sex, head size, scanner manufacturer, and field strength. Baseline data were used to test for differences in ROI volumes and memory between groups and to assess the within-group associations between ROI volumes and memory performance. We also evaluated changes in ROI volumes and memory over the follow-up interval by testing the main effects of time, group, and the group X time interactions. Lastly, we tested whether change in volume was associated with declines in memory.Results:At baseline, the aMCI group performed 2 SD below the CN group on episodic memory and exhibited smaller volumes in all AD-relevant regions (volumes 0.4 - 1.2 SD below CN group, ps < .041). There were no group differences in control region volumes. Memory performance was associated with volumes of the AD-relevant regions in the aMCI group (average rho = .51) but not with control regions. ROI volumes were not associated with memory in the CN group. At follow-up, the aMCI group continued to perform 2 SD below the CN group on episodic memory tests; however, change of performance over time did not differ between groups. The aMCI group continued to exhibit smaller volumes in all AD-relevant regions than the CN group, with greater declines in hippocampal volume (17% annual decline vs. 8% annual decline) and entorhinal volume (54% annual decline vs. 5% annual decline). There was a trending Group X Time interaction such that decrease in hippocampal volume was marginally associated with decline in memory for the aMCI group but not the CN group.Conclusions:Normative morphometric values generated from freely available software demonstrated expected patterns of group differences in AD-related volumes and associations with memory. Significant effects were localized to AD-relevant brain regions and only occurred in the aMCI group. These findings support the validity of these free tools as reliable and cost-effective alternatives to proprietary software.

Regional differences in the link between water exchange rate across the blood–brain barrier and cognitive performance in normal aging

The blood–brain barrier (BBB) undergoes functional changes with aging which may contribute to cognitive decline. A novel, diffusion prepared arterial spin labeling-based MRI technique can measure the rate of water exchange across the BBB (kw) and may thus be sensitive to age-related alterations in water exchange at the BBB. However, studies investigating relationships between kw and cognition have reported different directions of association. Here, we begin to investigate the direction of associations between kw and cognition in different brain regions, and their possible underpinnings, by evaluating links between kw, cognitive performance, and MRI markers of cerebrovascular dysfunction and/or damage. Forty-seven healthy older adults (age range 61–84) underwent neuroimaging to obtain whole-brain measures of kw, cerebrovascular reactivity (CVR), and white matter hyperintensity (WMH) volumes. Additionally, participants completed uniform data set (Version 3) neuropsychological tests of executive function (EF) and episodic memory (MEM). Voxel-wise linear regressions were conducted to test associations between kw and cognitive performance, CVR, and WMH volumes. We found that kw in the frontoparietal brain regions was positively associated with cognitive performance but not with CVR or WMH volumes. Conversely, kw in the basal ganglia was negatively associated with cognitive performance and CVR and positively associated with regional, periventricular WMH volume. These regionally dependent associations may relate to different physiological underpinnings in the relationships between kw and cognition in neocortical versus subcortical brain regions in older adults.

Neuropsychological function in psychosis of epilepsy

ObjectiveThe neuropsychological profile of patients with psychosis of epilepsy (POE) has received limited research attention. Recent neuroimaging work in POE has identified structural network pathology in the default mode network and the cognitive control network. This study examined the neuropsychological profile of POE focusing on cognitive domains subserved by these networks. MethodsTwelve consecutive patients with a diagnosis of POE were prospectively recruited from the Comprehensive Epilepsy Programmes at The Royal Melbourne, Austin and St Vincent's Hospitals, Melbourne, Australia between January 2015 and February 2017. They were compared to 12 matched patients with epilepsy but no psychosis and 42 healthy controls on standardised neuropsychological tests of memory and executive functioning in a case-control design. ResultsMean scores across all cognitive tasks showed a graded pattern of impairment, with the POE group showing the poorest performance, followed by the epilepsy without psychosis and the healthy control groups. This was associated with significant group-level differences on measures of working memory (p = < 0.01); immediate (p = < 0.01) and delayed verbal recall (p = < 0.01); visual memory (p < 0.001); and verbal fluency (p = 0.02). In particular, patients with POE performed significantly worse than the healthy control group on measures of both cognitive control (p = .005) and memory (p < .001), whereas the epilepsy without psychosis group showed only memory difficulties (delayed verbal recall) compared to healthy controls (p = .001). ConclusionPeople with POE show reduced performance in neuropsychological functions supported by the default mode and cognitive control networks, when compared to both healthy participants and people with epilepsy without psychosis.

Reduced concentration performance and heartbeat-evoked potential in individuals with a history of a SARS-CoV-2 infection

The goal of characterizing long-term psychological and neural consequences of a SARS-CoV-2 infection has recently gained importance. Here, we examined the effect of a prior SARS-CoV-2 infection on neural markers of exteroceptive (P300) and interoceptive (heartbeat-evoked potential; HEP) signal processing, as well as on neuropsychological tests of attention, inhibition and episodic memory, in 23 adults with a self-reported history of SARS-CoV-2 infection versus 23 healthy controls. We found that the group with a prior infection showed decreased HEP (but not P300) amplitudes, as well as reduced attention/concentration performance. These results suggest that SARS-CoV-2 may damage neural structures of cardiac interoception, thereby potentially contributing to cognitive and psychological long-term deficits. Modulations of interoceptive processing after a SARS-CoV-2 infection are thus a promising target for future research.

Memory-guided navigation in amyotrophic lateral sclerosis

BackgroundPrevious studies have yielded inconsistent results about hippocampal involvement in non-demented patients with amyotrophic lateral sclerosis (ALS). We hypothesized that testing of memory-guided spatial navigation i.e., a highly hippocampus-dependent behaviour, might reveal behavioural correlates of hippocampal dysfunction in non-demented ALS patients.MethodsWe conducted a prospective study of spatial cognition in 43 non-demented ALS outpatients (11f, 32 m, mean age 60.0 years, mean disease duration 27.0 months, mean ALSFRS-R score 40.0) and 43 healthy controls (14f, 29 m, mean age 57.0 years). Participants were tested with a virtual memory-guided navigation task derived from animal research (“starmaze”) that has previously been used in studies of hippocampal function. Participants were further tested with neuropsychological tests of visuospatial memory (SPART, 10/36 Spatial Recall Test), fluency (5PT, five-point test) and orientation (PTSOT, Perspective Taking/Spatial Orientation Test).ResultsPatients successfully learned and navigated the starmaze from memory, both in conditions that forced memory of landmarks (success: patients 50.7%, controls 47.7%, p = 0.786) and memory of path sequences (success: patients 96.5%, controls 94.0%, p = 0.937). Measures of navigational efficacy (latency, path error and navigational uncertainty) did not differ between groups (p ≥ 0.546). Likewise, SPART, 5PT and PTSOT scores did not differ between groups (p ≥ 0.238).ConclusionsThis study found no behavioural correlate for hippocampal dysfunction in non-demented ALS patients. These findings support the view that the individual cognitive phenotype of ALS may relate to distinct disease subtypes rather than being a variable expression of the same underlying condition.

Functional Network Alterations Associated with Cognition in Pre-Clinical Alzheimer's Disease.

Objective: Accumulation of cerebral amyloid-β (Aβ) is a risk factor for cognitive decline and defining feature of Alzheimer's disease (AD). Aβ is implicated in brain network disruption, but the extent to which these changes correspond with observable cognitive deficits in pre-clinical AD has not been tested. This study utilized individual-specific functional parcellations to sensitively evaluate the relationship between network connectivity and cognition in adults with and without Aβ deposition. Participants and Methods: Cognitively unimpaired adults ages 45-85 completed amyloid positron emission tomography, resting-state-functional magnetic resonance imaging (fMRI), and neuropsychological tests of episodic memory and executive function (EF). Participants in the upper tertile of mean standard uptake value ratio were considered Aβ+ (n = 50) while others were Aβ- (n = 99). Individualized functional network parcellations were generated from resting-state fMRI data. We examined the effects of group, network, and group-by-network interactions on memory and EF. Results: We observed several interactions such that within the Aβ+ group, preserved network integrity (i.e., greater connectivity within specific networks) was associated with better cognition, whereas network desegregation (i.e., greater connectivity between relative to within networks) was associated with worse cognition. This dissociation was most apparent for cognitive networks (frontoparietal, dorsal and ventral attention, limbic, and default mode), with connectivity relating to EF in the Aβ+ group specifically. Conclusions: Using an innovative approach to constructing individual-specified resting-state functional connectomes, we were able to detect differences in brain-cognition associations in pre-clinical AD. Our findings provide novel insight into specific functional network alterations occurring in the presence of Aβ that relate to cognitive function in asymptomatic individuals. Impact statement Elevated cerebral amyloid-β is a biomarker of pre-clinical Alzheimer's disease (AD). Associations between amyloidosis, functional network disruption, and cognitive impairment are evident in the later stages of AD, but these effects have not been substantiated in pre-clinical AD. Using individual-specific parcellations that maximally localize functional networks, we identify network alterations that relate to cognition in pre-clinical AD that have not been previously reported. We demonstrate that these effects localize to networks implicated in cognition. Our findings suggest that there may be subtle, amyloid-related alterations in the functional connectome that are detectable in pre-clinical AD, with potential implications for cognition in asymptomatic individuals.

Memory functioning after hippocampal removal: Does side matter?

To address the memory functioning after medial temporal lobe (MTL) surgery for refractory epilepsy and relationships with the side of the hippocampal removal, 22 patients with pharmaco-resistant epilepsy who had undergone MTL resection (10 right/12 left) at the Salpêtrière Hospital were compared with 21 matched healthy controls. We designed a specific neuropsychological binding memory test that specifically addressed hippocampal cortex functioning, and left-right material-specific lateralization. Our results showed that both left and right mesial temporal lobe removal cause a severe memory impairment, for both verbal and visual material. The removal of left medial temporal lobe causes worse memory impairment than the right removal regardless of the stimuli type (verbal or visual) questioning the theory of the hippocampal material-specific lateralization. The present study provided new evidence for the role of both hippocampus and surrounding cortices in memory-binding whatever the material type and also suggested that a left MTL removal is more deleterious for both verbal and visual episodic memory in comparison with right MTL removal.

Photobiomodulation improves frontal lobe cognitive functions and mental health of older adults with non-amnestic mild cognitive impairment: Case studies.

This study investigated the effects of transcranial photobiomodulation (tPBM) on improving the frontal lobe cognitive functions and mental health of older adults. Three older adults with mild cognitive impairment (MCI) of the non-amnestic type received 18-session tPBM stimulation for 9 weeks and were assessed with neuropsychological tests of memory and executive functions and standardized questionnaires on depressive and anxiety symptoms, global cognitive functions, and daily functioning abilities before and after tPBM stimulation. At baseline, their intrusion and/or perseveration errors in a verbal memory test and a fluency test, as measures of the frontal lobe cognitive functions, were in the borderline to severely impaired range at baseline. After tPBM stimulation, the three older adults showed various levels of improvement in their frontal lobe cognitive functions. One older adult's intrusion and perseveration errors improved from the <1st-2nd percentile (moderately to severely impaired range) to the 41st-69th percentile (average range), another older adult's intrusion errors improved from the 11th percentile to the 83rd percentile, and the third older adult's intrusion errors improved from the 5th percentile to the 56th percentile. Moreover, improvements in their anxiety and/or depressive symptoms were also observed. One older adult's depressive and anxiety symptoms improved from the severe range at baseline to the mild range after the intervention. The other two older adults' depressive symptoms improved from the mild range at baseline to the normal range after the intervention. These findings provide preliminary support for the potential of tPBM to improve the frontal lobe cognitive functions and mental health of older adults with MCI. Given the small sample size of only three older adults and the absence of a placebo control group, larger randomized controlled studies are needed to confirm its potential.

Preliminary Validity of a Telephone-Based Neuropsychological Battery in a Consecutive Series of Persons with HIV Disease Referred for Clinical Evaluation.

The COVID-19 pandemic necessitated use of remote assessments by clinical neuropsychologists. Telehealth was particularly important for vulnerable groups, including persons living with HIV (PLWH); however, limited internet access can be a serious barrier to care. This study examined the preliminary validity of a telephone-based neuropsychological assessment in a clinical sample of PLWH. A consecutive series of 59 PLWH were assessed via telephone at an HIV clinic in the southern U.S. between April 2020 and July 2022. The battery included auditory-verbal neuropsychological tests of memory, attention, and executive functions, and questionnaires assessing self-reported mood and activities of daily living (ADL). Study measures demonstrated acceptable internal consistency. PLWH demonstrated worse neuropsychological performance compared with expectations derived from the normal curve and an HIV-seronegative adult sample (N = 44). PLWH assessed via telephone demonstrated similar impairment rates to that of a consecutive series of PLWH (N = 41) assessed in-person immediately prior to the pandemic. Higher telephone-based global neuropsychological scores were related to younger age, more education, better fund of knowledge, White race/ethnicity, fewer medical conditions, and fewer depression symptoms. Global neuropsychological impairment was strongly and independently associated with greater dependence in ADL domains, particularly for instrumental activities. Although telephone-based approaches to neuropsychological assessment are not ideal, these data provide support for the feasibility, internal consistency, and preliminary validity of this method in a consecutive clinical series of PLWH. The direct comparability of telephone-based and in-person neuropsychological assessments remains to be determined by prospective, counterbalanced study designs examining both PLWH and seronegative individuals.

Empirically derived “discourse phenotypes” are associated with neuropsychological performance, cognitive status, and global atrophy: A latent profile analysis of connected speech measures

AbstractBackgroundEvidence suggests that “connected speech” (i.e., spoken language, as in discourse) is related to early cognitive decline and early Alzheimer’s disease and related dementias (ADRD), yet performance on speech tasks and cognitive performance in ADRD are notably heterogeneous. Here we examined whether unique spoken language phenotypes could be ascertained using latent profile analysis (LPA), and we examined the association of identified clusters to demographic, clinical and cognitive characteristics. In the subsets with amyloid PET and structural MR, we analyzed cluster associations with estimated amyloid DVR and/or global atrophy at or near the speech sample.Method1,039 participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) completed comprehensive neuropsychological testing and provided a spoken language digital recording describing the Cookie Theft picture from the Boston Diagnostic Aphasia Examination. Cognitive status was determined by consensus conference. Five speech‐language metrics based on previous literature (Table 1) were automatically extracted from transcriptions of recordings utilizing Computerized Language Analysis (CLAN), including: semantic content, sentence length, speaking rate, and fluency. Baseline speech metric Z‐scores were included in the LPA; model fits were evaluated using BIC criteria. T‐tests, chi‐square tests, and ANCOVAs were used to the compare demographic, clinical, cognitive and imaging characteristics of the resulting discourse phenotypes (alpha = .05).ResultFit indices suggested a 3‐profile model: normal content‐normal fluency (n = 558), low content‐normal fluency (n = 224), and low content‐low fluency (n = 257) (Figure 1). The three phenotypes differed on gender and cognitive status, with more men and a higher proportion of MCI in the low content‐low fluency phenotype than the other groups; the phenotypes also differed on concurrent neuropsychological tests of language, memory and executive function. In the subset with imaging, the low content‐low fluency phenotype showed the most global atrophy. There were no differences in concurrent estimated amyloid accumulation (Table 2, Figure 2).ConclusionThree phenotypes of narrative discourse were identified and were associated with multiple neuropsychological tests, overall cognitive status and global brain atrophy. While connected speech metrics are generally viewed as a promising ADRD digital biomarker, the underlying taxonomy identified here suggests a more precision‐based approach is possible.

Validity of a remote supervised preclinical Alzheimer’s disease cognitive composite (PACC) score in preclinical and prodromal Alzheimer’s disease.

AbstractBackgroundNeuropsychological tests administered to individuals in locations different from the assessor (i.e., remote assessment) can provide substantial reductions in patient burden, study cost and barriers to access. However, such tests must be optimized and validated for use in remote settings. The preclinical cognitive composite score (PACC) is derived from neuropsychological tests of episodic memory, complex attention, and general mental status. This study determined whether a set of neuropsychological tests of these domains, which can provide a PACC score, can be given in a remote supervised setting and remain sensitive to AD related cognitive impairment.MethodOlder adults classified as cognitively unimpaired (CU, n = 30), preclinical AD (n = 30) or prodromal AD (n = 25), with conventional PACC scores known, completed three computerized tests; the International Shopping list Test (ISLT), Continuous Paired Associate Learning Test (CPAL) and the International Digit Symbol Substitution Test, while supervised by a neuropsychologist in in‐clinic and remote settings. All individuals then completed the remote assessments two more times 7days (+/‐4 days) apartResultMain performance measure from each test on each assessment was standardized using the mean and SD of the CU group, assessed under supervision, at baseline. Standardized scores for each assessment were then averaged to yield a PACC score. There was no difference in rates of missing data or group mean score on individual test scores or PACC score, between in‐clinic and remote settings. Compared to the CU group, impairment in performance on the digital PACC in the prodromal AD was substantial (z = ‐1.56) but equivalent between in clinic (9z = 1.57) and remote (z = ‐1.56) settings. Performance on the digital PACC was slightly worse in the preclinical AD group (z = –0.42) but did not differ for settings. The reliability of the digital PACC score was very high (r = 0.87).ConclusionThe digital PACC derived from neuropsychological tests given in remote supervised contexts is acceptable, valid, reliable and sensitive to AD related cognitive impairment when given in‐clinic or remotely.

Teleneuropsychology: normative data for the assessment of memory in online settings

IntroductionThe COVID-19 pandemic has forced significant changes in clinical practice. Psychologists and neuropsychologists had to modify their settings to assess patients’ abilities, switching from an in-person modality to a remote setting by using video calling platforms. Consequently, this change brought about the need for new normative data tailored to remote settings.Aim and methodsThe study aimed to develop normative data for the online assessment of neuropsychological memory tests and to compare it with the published norms obtained in standard settings. Two hundred and four healthy Italian volunteers performed three verbal memory tests through the Google Meet platform: the Digit Span (Backward and Forward), the Rey Auditory Verbal Learning, and the Verbal Paired Associated Learning Test.ResultsThis research provides specific norms that consider the influence of demographic characteristics. Their comparison with published norms shows a medium to high agreement between systems. The present study provides a reference for the clinical use of neuropsychological instruments to assess verbal memory in a remote setting and offers specific recommendations.

Why do mothers never stop grieving for their deceased children? Enduring alterations of brain connectivity and function.

A child’s death is a profound loss for mothers and affects hundreds of thousands of women. Mothers report inconsolable and progressive grief that is distinct from depression and impacts daily emotions and functions. The brain mechanisms responsible for this relatively common and profound mental health problem are unclear, hampering its clinical recognition and care. In an initial exploration of this condition, we used resting state functional MRI (fMRI) scans to examine functional connectivity in key circuits, and task-based fMRI to examine brain network activity in grieving mothers in response to pictures of their deceased child and as well as recognizable deceased celebrities and unfamiliar individuals. We compared nine mothers who had lost an adult child and aged-matched control mothers with a living child of a similar age. Additionally, we collected diffusion imaging scans to probe structural connectivity and complemented the imaging studies with neuropsychological assessments. Increased functional activation in Ventral Attention/Salience Networks accompanied by a reduced activation in the medial prefrontal cortex in response to the deceased child’s picture robustly distinguished the grieving mothers from controls. Heightened resting-state functional connectivity between the paraventricular thalamic nucleus (PVT) and the amygdala distinguished the grieving mothers from the controls and correlated with subjective grief severity. Structurally, maternal grief and its severity were associated with alterations in corticolimbic white matter tracts. Finally, grieving mothers performed worse than controls on neuropsychological tests of learning, memory, and executive function, linked with grief severity. Reduced activation in cortical regions inhibiting emotions and changes in the PVT circuitry—a region involved in long-term emotional memories and decision making under conflict—distinguish grieving mothers from controls. Notably, the magnitude of neurobiological changes correlates with the subjective severity of grief. Together, these new discoveries delineate a prevalent and under-recognized mental health syndrome and chart a path for its appreciation and care.