Evidence for reduced anti-inflammatory microglial phagocytic response in late-life major depression.

Major depressive disorder (MDD) is associated with Alzheimer's disease (AD) but the precise mechanisms underlying this relationship are not understood. While it is well established that cerebrospinal fluid (CSF) soluble levels of triggering receptor expressed on myeloid cells 2 (sTREM2) increase during early stages of AD, how sTREM2 levels behave in subjects with MDD is not known. In a longitudinal study, we measured CSF sTREM2 levels in 27 elderly cognitively intact individuals with late-life major depression (LLMD) and in 19 healthy controls. We tested the hypothesis that, similarly to what happens in early stages of AD, CSF sTREM2 would be elevated in MDD. In addition, we compared the associations of CSF sTREM2, pro- and anti- inflammatory, and AD biomarkers in LLMD and control subjects. Surprisingly, we found that mean CSF sTREM2 levels were significantly reduced in LLMD compared to controls. This reduction was no longer significant at the 3-year follow-up visit when depression severity improved. In addition, we found that CSF sTREM2 was associated with AD biomarkers and proinflammatory cytokines in controls but not in LLMD. These findings suggest that impaired microglia phagocytic response to AD pathology may be a novel link between MDD and AD.

CSF α-synuclein correlates with CSF neurogranin in late-life depression.

Purpose/aim of the study: Major depressive disorder (MDD) in late life is linked to increased risk of subsequent dementia, but it is still unclear exactly what pathophysiological mechanisms underpin this link. A potential mechanism related to elevated risk of dementia in MDD is increased levels of α-synuclein (α-Syn), a protein found in presynaptic neuronal terminals.Materials and methods: In this study, we examined cerebrospinal fluid (CSF) levels of α-Syn in conjunction with biomarkers of neurodegeneration (amyloid-ß 42, total and phospho tau) and synaptic dysfunction (neurogranin), and measures of memory ability, in 27 cognitively intact older individuals with MDD and 19 controls.Results: Our results show that CSF α-Syn levels did not significantly differ across depressed and control participants, but α-Syn was directly associated with neurogranin levels, and indirectly linked to poorer memory ability.Conclusions: All in all, we found that α-Syn may be implicated in the association between late life MDD and synaptic dysfunction, although further research is needed to confirm these results.

Age-related prefrontal cortex activation in associative memory: An fNIRS pilot study.

Older adults typically perform more poorly than younger adults in free recall memory tests. This age-related deficit has been linked to decline of brain activation and brain prefrontal lateralization, which may be the result of compensatory mechanisms. In the present pilot study, we investigated the effect of age on prefrontal cortex (PFC) activation during performance of a task that requires memory associations (temporal vs. spatial clustering), using functional Near-Infrared Spectroscopy (fNIRS). Ten younger adults, ten cognitively high-performing older individuals, and ten low-performing older individuals completed a free recall task, where either a temporal or spatial strategy (but not both simultaneously) could be employed to retrieve groups of same-category stimuli, whilst changes in PFC hemodynamics were recorded by means of a 12-channel fNIRS system. The results suggest PFC activation, and right lateralization specific to younger adults. Moreover, age did not affect use of memory organization, given that temporal clustering was preferred over spatial clustering in all groups. These findings are in line with previous literature on the aging brain and on temporal organization of memory. Our results also suggest that the PFC may be specifically involved in memory for temporal associations. Future research may consider whether age-related deficits in temporal organization may be an early sign of PFC pathology and possible neurodegeneration.

The recency ratio is related to CSF amyloid beta 1-42 levels in MCI-AD.

OBJECTIVE: As anti-amyloid therapeutic interventions shift from enrolling patients with Alzheimer's disease (AD) dementia to individuals with pre-clinical disease, the need for sensitive measures that allow for non-invasive, fast, disseminable, and cost-effective identification of preclinical status increases in importance. The recency ratio (Rr) is a memory measure that relies on analysis of serial position performance, which has been found to predict cognitive decline and conversion to early mild cognitive impairment (MCI). The aim of this study was to test Rr's sensitivity to cerebrospinal fluid (CSF) levels of the core AD biomarkers in individuals with MCI-AD and controls. METHODS: Baseline data from 126 (110 controls and 16 MCI-AD) participants from the Wisconsin Alzheimer's Disease Research Center were analysed. Partial correlations adjusting for demographics were carried out between CSF measure of amyloid beta (Aß40, Aß42, and the 40/42 ratio) and tau (total and phosphorylated), and memory measures (Rr, delayed recall, and total recall) derived from the Rey's Auditory Verbal Learning Test. RESULTS: Results indicated that Rr was the most sensitive memory score to Aß42 levels in MCI-AD, while no memory score correlated significantly with any biomarker in controls. CONCLUSIONS: This study shows that Rr is a sensitive cognitive index of underlying amyloid ß pathology in MCI-AD.

The recency ratio as predictor of early MCI.

ABSTRACTObjectives:Individuals with Alzheimer's disease (AD) present poor immediate primacy recall accompanied by intact or exaggerated recency, which then tends to decline after a delay. Bruno et al. (Journal of Clinical and Experimental Neuropsychology, Vol. 38, 2016, pp. 967-973) have shown that higher ratio scores between immediate and delayed recency (i.e. the recency ratio; Rr) are associated with cognitive decline in high-functioning older individuals. We tested whether Rr predicted conversion to early mild cognitive impairment (early MCI) from a cognitively healthy baseline. DESIGN: Data were analyzed longitudinally with binomial regression. Baseline scores were used to predict conversion to early MCI after approximately nine years. SETTING: Data were collected at the Wisconsin Registry of Alzheimer's Prevention, in Madison, Wisconsin. PARTICIPANTS: For the study, 427 individuals were included in the analysis; all participants were 50 years of age or older and cognitively intact at baseline, and were native English speakers. MEASUREMENTS: Memory data were collected using the Rey's Auditory Verbal Learning Test, and the early MCI diagnosis was obtained via consensus conference. RESULTS: Our results showed that higher Rr scores are correlated with greater risk of later early MCI diagnosis, and this association is independent of total recall performance. CONCLUSIONS: Rr is an emerging cognitive marker of cognitive decline.

The recency ratio is associated with reduced CSF glutamate in late-life depression.

Glutamate is the principal excitatory neurotransmitter in the central nervous system, and is thought to be involved in the process of memory encoding and storage. Glutamate disturbances have also been reported in psychiatric disorders, such as schizophrenia and major depressive disorder (MDD), and in Alzheimer's disease. In this paper, we set out to study the relationship between cerebrospinal fluid (CSF) glutamate levels and memory performance, which we believe has not been reported previously. In particular, we focused on recall performance broken down by serial position. Our prediction was that the recency ratio (Rr), a novel cognitive marker of intellectual impairment, would be linked with CSF glutamate levels. We studied data from a group of cognitively intact elderly individuals, 28 of whom had MDD, while 19 were controls. Study results indicated that Rr levels, but no other memory score, were inversely correlated with CSF glutamate levels, although this was found only in individuals with late-life MDD. For comparison, glutamine or GABA were not correlated with any memory performance measure.

Bilingualism, Language Disorders and Intercultural Families in Contemporary Italy: Family Relations, Transmission of Language and Representations of Otherness.

This study aims to show how language disorders in children affect language transmission and the mixedness experience in intercultural families. To this end, it adopts a qualitative method of study based on the administration of ad hoc interviews to intercultural couples who consulted our Child Neuropsychiatry Service because of language disorders in their children. One of the main consequences, when the child of an intercultural couple presents a language disorder and a diagnostic process has to be initiated, may be interruption of the transmission of the second language, especially if it is the mother's language. The decision to do this, which may be taken on the advice of teachers and health professionals, but also because the parents themselves often attribute their child's language disorder to his bilingual condition, affects not only the relationship between the mother and her child, but also processes in the construction of parenthood and in the structuring of the child's personality and the plurality of his affiliations. A clear understanding of how the dialectic between the categories of "alien" and "familiar" is managed in these contemporary families, which have to reckon with the condition of otherness, is crucial for psychiatrists and psychotherapists working in settings in which cultural difference is an issue to consider.

Detection of sexual orientation ("gaydar") by homosexual and heterosexual women.

Although there has been considerable research investigating the ability to identify sexual orientation from static images, or "gaydar," few studies have considered the role of female sexual orientation or sexual interest (for example, sociosexual orientation) in judgment accuracy. In two studies, we investigated the sexuality detection ability, and masculinity and femininity as cues used in judgment. In Study 1, we recruited heterosexual (N = 55) and homosexual (N = 71) women to rate the sexual orientation of homosexual and heterosexual male and female targets (N = 80: 20 heterosexual men, 20 homosexual men, 20 heterosexual women, and 20 homosexual women). We found that detection accuracy was better than chance levels for both male and female targets and that male targets were more likely to be falsely labeled as homosexual than female targets were. Overall, female faces were more accurately identified as heterosexual or homosexual than male faces and homosexual female raters were biased towards labeling targets as homosexual. Sociosexuality did not influence the accuracy with which targets were identified as heterosexual or homosexual. In Study 2, 100 heterosexual and 20 homosexual women rated the stimulus for masculinity and femininity. Heterosexual women were rated as more feminine and less masculine than homosexual women and homosexual men were rated as more feminine and less masculine than heterosexual men. Sexual orientation of the judges did not affect the ratings. The results were discussed with a reference to evolutionary and cultural influences affecting sexual orientation judgment accuracy.

Memory bias for negative emotional words in recognition memory is driven by effects of category membership.

Recognition memory studies often find that emotional items are more likely than neutral items to be labelled as studied. Previous work suggests this bias is driven by increased memory strength/familiarity for emotional items. We explored strength and bias interpretations of this effect with the conjecture that emotional stimuli might seem more familiar because they share features with studied items from the same category. Categorical effects were manipulated in a recognition task by presenting lists with a small, medium or large proportion of emotional words. The liberal memory bias for emotional words was only observed when a medium or large proportion of categorised words were presented in the lists. Similar, though weaker, effects were observed with categorised words that were not emotional (animal names). These results suggest that liberal memory bias for emotional items may be largely driven by effects of category membership.

Cognitive reserve and emotional stimuli in older individuals: level of education moderates the age-related positivity effect.

UNLABELLED: BACKGROUND/STUDY CONTEXT: A frequently observed age-related effect is a preference in older individuals for positive stimuli. The cognitive control model proposes that this positivity effect may be mediated by executive functions. We propose that cognitive reserve, operationally defined as years of education, which tempers cognitive decline and has been linked to executive functions, should also influence the age-related positivity effect, especially as age advances. METHODS: An emotional free recall test was administered to a group of 84 cognitively intact individuals aged 60 to 88, who varied in years of education. As part of a larger test battery, data were obtained on measures of executive functioning and depression. RESULTS: Multiple regression and moderation analyses were performed, controlling for general cognitive function, severity of depressive symptoms, and executive function. In our data, years of education appeared to moderate the effect of age on the positivity effect; age was negatively associated with recall of positive words in participants with fewer years of education, whereas a nonsignificant positive correlation was observed between age and positivity in participants with more education. CONCLUSION: Cognitive reserve appears to play a role in explaining individual differences in the positivity effect in healthy older individuals. Future studies should investigate whether cognitive reserve is also implicated in the ability to process a wide range of emotional stimuli and whether greater reserve is reflected in improved emotional regulation.

Delayed primacy recall performance predicts post mortem Alzheimer's disease pathology from unimpaired ante mortem cognitive baseline.

We propose a novel method to assess delayed primacy in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) memory test. We then examine whether this measure predicts post mortem Alzheimer's disease (AD) neuropathology in individuals who were clinically unimpaired at baseline. A total of 1096 individuals were selected from the Rush Alzheimer's Disease Center database registry. All participants were clinically unimpaired at baseline, and had subsequently undergone brain autopsy. Average age at baseline was 78.8 (6.92). A Bayesian regression analysis was carried out with global pathology as an outcome; demographic, clinical, and apolipoprotein E (APOE) data as covariates; and cognitive predictors, including delayed primacy. Global AD pathology was best predicted by delayed primacy. Secondary analyses showed that delayed primacy was mostly associated with neuritic plaques, whereas total delayed recall was associated with neurofibrillary tangles. Sex differential associations were observed. We conclude that CERAD-derived delayed primacy is a useful metric for early detection and diagnosis of AD in unimpaired individuals. Highlights: We propose a novel method to analyse serial position in the CERAD memory test.We analyse data from 1096 individuals who were cognitively unimpaired at baseline.Delayed primacy predicts post mortem pathology better than traditional metrics.

A comparison of story-recall metrics to predict hippocampal volume in older adults with and without cognitive impairment.

Objective: Process-based scores of episodic memory tests, such as the recency ratio (Rr), have been found to compare favourably to, or to be better than, most conventional or "traditional" scores employed to estimate memory ability in older individuals (Bock et al., 2021; Bruno et al., 2019). We explored the relationship between process-based scores and hippocampal volume in older adults, while comparing process-based to traditional story recall-derived scores, to examine potential differences in their predictive abilities. Methods: We analysed data from 355 participants extracted from the WRAP and WADRC databases, who were classified as cognitively unimpaired, or exhibited mild cognitive impairment (MCI) or dementia. Story Recall was measured with the Logical Memory Test (LMT) from the Weschler Memory Scale Revised, collected within twelve months of the magnetic resonance imaging scan. Linear regression analyses were conducted with left or right hippocampal volume (HV) as outcomes separately, and with Rr, Total ratio, Immediate LMT, or Delayed LMT scores as predictors, along with covariates. Results: Higher Rr and Tr scores significantly predicted lower left and right HV, while Tr showed the best model fit of all, as indicated by AIC. Traditional scores, Immediate LMT and Delayed LMT, were significantly associated with left and right HV, but were outperformed by both process-based scores for left HV, and by Tr for right HV. Conclusions: Current findings show the direct relationship between hippocampal volume and all the LMT scores examined here, and that process-based scores outperform traditional scores as markers of hippocampal volume.

Associations between recall of proper names in story recall and CSF amyloid and tau in adults without cognitive impairment.

Neuropsychological measures sensitive to decline in the preclinical phase of Alzheimer's disease are needed. We previously demonstrated that higher amyloid-beta (Aß) assessed by positron emission tomography in adults without cognitive impairment was associated with recall of fewer proper names in Logical Memory story recall. The current study investigated the association between proper names and cerebrospinal fluid biomarkers (Aß42/40, phosphorylated tau181 [pTau181], neurofilament light) in 223 participants from the Wisconsin Registry for Alzheimer's Prevention. We assessed associations between biomarkers and delayed Logical Memory total score and proper names using binary logistic regressions. Sensitivity analyses used multinomial logistic regression and stratified biomarker groups. Lower Logical Memory total score and proper names scores from the most recent visit were associated with biomarker positivity. Relatedly, there was a 27% decreased risk of being classified Aß42/40+/pTau181+ for each additional proper name recalled. A linear mixed effects model found that longitudinal change in proper names recall was predicted by biomarker status. These results demonstrate a novel relationship between proper names and Alzheimer's disease-cerebrospinal fluid pathology.

Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline.

INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid. RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline. DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.

[Care outside the hospital walls]. / Un soin hors les murs.

Physical activity can benefit people suffering from mental disorders, on the condition however that it is closely supervised by caregivers. It enables patients and caregivers to leave the hospital, physically, as well as figuratively speaking, by offering another space in which the nurse-patient relationship can bear fruit.

Delayed primacy recall performance predicts post mortem Alzheimer's disease pathology from unimpaired ante mortem cognitive baseline.

INTRODUCTION: We propose a novel method to assess delayed primacy in the CERAD memory test. We then examine whether this measure predicts post mortem Alzheimer's disease (AD) neuropathology in individuals who were clinically unimpaired at baseline. METHODS: A total of 1096 individuals were selected from the Rush Alzheimer's Disease Center database registry. All participants were clinically unimpaired at baseline, and had subsequently undergone brain autopsy. Average age at baseline was 78.8 (6.92). A Bayesian regression analysis was carried out with global pathology as outcome; demographic, clinical and APOE data as covariates; and cognitive predictors, including delayed primacy. RESULTS: Global AD pathology was best predicted by delayed primacy. Secondary analyses showed that delayed primacy was mostly associated with neuritic plaques, whereas total delayed recall was associated with neurofibrillary tangles. DISCUSSION: We conclude that CERAD-derived delayed primacy is a useful metric for early detection and diagnosis of AD in unimpaired individuals.

Comparison of the 10-, 14- and 20-Item CES-D Scores as Predictors of Cognitive Decline.

The association between depressive symptomatology and cognitive decline has been examined using the Centre for Epidemiologic Studies-Depression Scale (CES-D); however, concerns have been raised about this self-report measure. Here, we examined how the CES-D total score from the 14- and 10-item versions compared to the 20-item version in predicting progression to cognitive decline from a cognitively unimpaired baseline. Data from 1054 participants were analysed using ordinal logistic regression, alongside moderator and receiver-operating characteristics curve analyses. All baseline total scores significantly predicted progression to cognitive decline. The 14-item version was better than the 20-item version in predicting consensus diagnosis, as shown by their AICs, while also showing the highest accuracy when discriminating between participants by diagnosis at last visit. We did not find sex to moderate the relationship between CES-D score and cognitive decline. Current findings suggest the 10- and 14-item versions of the CES-D are comparable to the 20-item version, and that the 14-item version may be better at predicting longitudinal consensus diagnosis compared to the 20-item version.

Health-related quality of life among people living with HIV in the era of universal test and treat: results from a cross-sectional study in KwaZulu-Natal, South Africa.

BACKGROUND: The World Health Organisation's (WHO) key population-based strategy for ending the human immunodeficiency virus (HIV) epidemic is universal HIV test and treat (UTT) along with pre-exposure prophylaxis (PrEP), and post-exposure prophylaxis (PEP). Despite the successful scale-up of the UTT strategy in sub-Saharan Africa (SSA), the quality of life (QoL) of people living with HIV (PLHIV) remains sub-optimal. Poor QoL in PLHIV may threaten the UNAIDS 95-95-95 programme targets. Monitoring QoL of PLHIV has become a key focus of HIV research among other outcomes so as to understand health-related QoL (HRQoL) profiles and identify interventions to improve programme performance. This study aimed to describe HRQoL profiles and identify their predictors in PLHIV in KwaZulu Natal, South Africa. METHODS: We conducted a secondary data analysis of a cross-sectional survey conducted between May and June 2022 among PLHIV (n = 105) accessing HIV services at an outpatient clinic in KwaZulu-Natal, South Africa. Socio-demographic, HRQoL (EQ-5D-5L index scores), clinical data, depressive symptoms (CES-D-10), and viral load data were collected from all participants. We examined predictors of HRQoL using generalised linear models controlling for age and sex. RESULTS: The mean age of the participants was 45 years (SD = 13). The proportion of participants with disabilities and comorbidities were 3% and 18%, respectively. Depressive symptoms were present in 49% of the participants. Participant's mean EQ-5D-5L index score was 0.87 (SD = 0.21) and ranged from 0.11 to 1.0. The mean general health state (EQ-VAS) was 74.7 (SD = 18.8) and ranged from 6 to 100. Factors that reduced HRQoL were disability (ß = -0.607, p ≤ 0.001), comorbidities (ß = - 0.23, p ≤ 0.05), presence of depressive symptoms (ß = -0.10, p ≤ 0.05), and old age (ß = -0.04, p ≤ 0.05). Factors that increased HRQoL were a good perceived health state (ß = 0.147, p ≤ 0.001) and availability of social support (ß = 0.098, p ≤ 0.05). CONCLUSION: A combination of old age (60 years and above), any disability and comorbidities had a considerable effect on HRQoL among PLHIV. Our findings support the recommendation for an additional fourth UNAIDS target that should focus on ensuring that 95% of PLHIV have the highest possible HRQoL. Psycho-social support interventions are recommended to improve the HRQoL of PLHIV.