Global Cognitive Measures Research Articles

Association of cognitive and structural correlates of brain aging and incident epilepsy. The Framingham Heart Study.

Late-onset epilepsy has the highest incidence among all age groups affected by epilepsy and often occurs in the absence of known clinical risk factors such as stroke and dementia. There is increasing evidence that brain changes contributing to epileptogenesis likely start years before disease onset, and we aim to relate cognitive and imaging correlates of subclinical brain injury to incident late-onset epilepsy in a large, community-based cohort. We studied Offspring Cohort of the Framingham Heart Study participants 45 years or older, who were free of prevalent stroke, dementia, or epilepsy, and had neuropsychological (NP) evaluation and brain magnetic resonance imaging (MRI). Cognitive measures included Visual Reproduction Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making Test B minus A (TrTB-TrTA; attention and executive function), and a global measure of cognition derived from principal component analysis. MRI measures included total cerebral brain volume, cortical gray matter volume (CGMV), white matter hyperintensity volume (WMHV), and hippocampal volume. Incident epilepsy was identified through a review of administrative data and medical records. Cox proportional hazards regression models were used for the analyses. All analyses were adjusted for age, sex, and educational level (cognition only). Among participants who underwent NP testing (n = 2349, 45.81% male), 31 incident epilepsy cases were identified during follow-up. Better performance on the TrTB-TrTA was associated with a lower risk of developing epilepsy (hazard ratio [HR] .25, 95% confidence interval [CI] .08-.73; p = .011). In the subgroup of participants with MRI (n = 2056, 46.01% male), 27 developed epilepsy. Higher WMHV was associated with higher epilepsy risk (HR 1.5, 95%CI 1.01-2.20; p = .042), but higher CGMV (HR .73, 95% CI .57-.93; p = .001) was associated with lower incidence of epilepsy. Better performance on the (TrTB-TrTA), a measure of executive function and attention, and higher cortical volumes are associated with lower risk of developing epilepsy. Conversely, higher WMHV, a measure of occult vascular injury, increases the risk. Our study shows that non-invasive tests performed in mid-life may help identify people at risk for developing epilepsy later in life.

Cortico-limbic volume abnormalities in late life depression are distinct from β amyloid and white matter pathologies.

This study was conducted to clarify patterns of cortico-limbic volume abnormalities in late life depression (LLD) relative to non-depressed (ND) adults matched for amyloid β (Aβ) deposition and to evaluate the relationship of volume abnormalities with cognitive performance. Participants included 116 LLD and 226 ND. Classification accuracy of LLD status was estimated using area under the receiver operator characteristic curve. Twenty-one percent of LLD and ND participants were Aβ positive and the groups did not differ on white matter hyperintensity volume (WMH (logscale); β = 0.12, p = 0.28). Compared to ND, the LLD group exhibited significantly lower bilateral volume in the lateral orbitofrontal cortex, hippocampus, accumbens area, superior temporal lobe, temporal pole, and amygdala after multiple comparison correction (p < 0.009 for all). Cortico-limbic volumes significantly improved classification of LLD beyond demographic characteristics, Aβ status, and WMH (AUCVol = 0.71, AUCWMH, Aβ = 0.62, AUC difference, 0.09 [0.03 to 0.15]). LLD exhibited poorer performance on measures of global cognition, set shifting, and verbal learning and memory relative to ND. Cognitive function was positively associated with cortico-limbic volumes and these relationships did not differ by group. Secondary analyses with an ND sample additionally matched for Mild Cognitive Impairment (MCI) diagnosis showed a similar but attenuated pattern of volume abnormalities. Overall, our results support LLD as being associated with cortico-limbic volume abnormalities that are distinct from Aβ and white matter pathologies and that these volume abnormalities are important factors associated with cognitive dysfunction in LLD.

Association between social networks and cognition among middle-aged and older adults in rural India.

Prior studies using global cognitive measures have shown that social connectedness is linked with cognitive performance. We investigate the role of different social network dimensions on performance across distinct cognitive domains among dementia-free middle-aged and older rural Indians. We utilized baseline assessment data of 2,525 participants (≥45 years) of an ongoing, prospective, aging cohort in rural India (Srinivaspura Aging, Neuro Senescence, and COGnition) for this study. We evaluated social networks using Cohen's Social Network Index on three dimensions: network diversity, network size, and network embeddedness. We measured cognitive performance on memory (narrative recall), visuospatial ability (geometric figure spatial recognition, visuospatial span), language (verbal fluency, semantic association, word comprehension, reading comprehension), and attention domains of a culturally adapted, computerized, neurocognitive test battery. Linear regression models, adjusted for age and sex, were used for statistical analysis. In the linear regression model adjusted for age and sex, we found that greater network diversity was significantly associated with better performance in narrative recall, geometric figure spatial recognition, reading comprehension, semantic association, and attention tests. Participants with a larger network size had significantly better performance in verbal fluency and semantic association tests. Further, participants with greater network embeddedness had better visuospatial span and verbal fluency. Individuals having a greater network diversity, larger network size, and greater network embeddedness had better cognitive performance in multiple distinct cognitive domains. Following up these participants with serial cognitive monitoring can help understand if social networks play a role in delaying cognitive decline and protecting against dementia. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Physical Activity in Mild Vascular Cognitive Impairment: Results of the AFIVASC Randomized Controlled Trial at 6 Months.

Vascular cognitive impairment is frequent, in mild (mVCI) or severe forms (vascular dementia). To do a randomized controlled-trial to evaluate the impact of physical activity on cognition (primary outcome), neurocognitive measures, quality of life, functional status, and physical function (secondary outcomes), in patients with mVCI. A hundred and four patients with mVCI (mean age 71.2 years; 53 women) were randomized for a six-month intervention of moderate physical activity (60-minute sessions, 3 times/week) (n = 53) or best-practice "usual care" (n = 51). Comprehensive evaluations of primary and secondary outcomes included an objective measure of physical activity through accelerometry at baseline and after intervention. Mean session attendance was 58%. Adverse events were negligible. After 6 months, no significant primary outcome change was observed, either in the intervention or 'usual care' group. The intervention group improved significantly in some secondary outcomes in physical function - aerobic capacity (U = 403; p = 0.000) and agility (U = 453; p = 0.005) after 6 months. Regardless of randomization arm, a post-hoc analysis based on fulfilling at least 21.5 minutes/day of moderate or 10.7 minutes/day of vigorous physical activity (World Health Organization-WHO standards) revealed improvements. These were not only in motor capacity but also on the global measure of cognition, executive functions and memory. Physical activity was safe and beneficial regarding domains of physical function. No significant cognitive decline was registered over 6-months, regardless of intervention allocation. Larger samples, longer follow-ups and focus on intervention adherence are needed to fully analyze the impact of WHO recommendations for physical activity in mVCI populations.

Neuroprotective Dietary Patterns and Longitudinal Changes in Cognitive Function in Older Adults

BackgroundNumerous studies have examined the association between neuroprotective diets and cognitive function during aging; however, these studies have produced divergent findings. Some studies find that greater adherence to these dietary patterns is associated with preserved cognition, whereas others find no effect. ObjectiveThe aim of this study was to examine the association of the Mediterranean, the Dietary Approach to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegeneration Delay (MIND) dietary patterns with global cognition over 4 waves of data from the Health and Retirement Study, a longitudinal panel study conducted at the University of Michigan. DesignThis is a longitudinal secondary data analysis using Health and Retirement Study data drawn from the Food Frequency Questionnaire completed as part of the Health Care and Nutrition Survey administered in 2013 to 2014, neuropsychological assessment data obtained from the Core questionnaire in 2014, 2016, 2018, and 2020, and demographic data from the Core questionnaire in 2014. Participants/settingParticipants with total daily energy intake below 600 or 800 kcal and above 6000 and 8000 kcal for women and men, respectively, were excluded based on criteria from a similar study using the same dataset. In addition, participants with a diagnosis of dementia, Alzheimer disease, or stroke as of 2014 were excluded. There were 6154 participants in the Mediterranean diet and DASH diet analyses and 5143 participants in the MIND diet analyses. Main outcome measureA global cognitive measure incorporating immediate and delayed recall, serial 7s, and backward counting scores was calculated for each participant at each wave. Statistical analysisThe primary analyses examined the association between each diet type and cognition over 4 waves using separate multilevel models that controlled for age, gender, self-rated health, years of education, total energy intake, weekly exercise, and body mass index. ResultsMediterranean and DASH diet adherence were positively and significantly associated with baseline cognition and were associated with slower cognitive decline over a 6-year period. MIND diet adherence was positively and significantly correlated with baseline cognition but was not significantly associated with slower cognitive decline over a 6-year period. Cross-level interactions for adherence to each dietary pattern and cognitive change over time, computed with standardized diet scores, were as follows: Mediterranean diet (β = .03; P = .002), DASH diet (β = .04; P = .004), and MIND diet (β = .02; P = .094). ConclusionsThe Mediterranean, DASH, and MIND dietary patterns are associated with better cognitive performance at baseline and the Mediterranean and DASH diets were associated with slower cognitive decline over time. Adherence to the DASH diet had the greatest magnitude of association with baseline cognition and rate of cognitive change.

Negative global metacognitive biases are associated with depressive and posttraumatic stress disorder symptoms and improve with targeted or game-based cognitive training.

Metacognition is disrupted in several clinical populations. One aspect of metacognition, global metacognitive bias (difference between objective and self-reported abilities), has shown to be particularly relevant to clinical functioning. However, previous studies of global metacognitive biases in populations with elevated depressive/posttraumatic stress disorder (PTSD) symptoms have not measured objective and self-reported abilities relative to normative samples, limiting the quantification of biases. Additionally, few studies have examined whether cognitive interventions can improve metacognitive biases or how this relates to depressive/PTSD symptom severity. A total of 84 participants with mild traumatic brain injury (77% veterans) performed PTSD and depression assessments along with self-reported and objective measures of global cognition. Age-adjusted norm-based z scores were used for self-reported and objective cognition, and bias was calculated by subtracting objective minus self-report scores. Participants then received 13 weeks of targeted cognitive training or entertainment games training (both providing performance feedback). Participants were assessed at baseline, immediately posttraining, and 3 months posttraining. We found large negative metacognitive biases in those with clinically significant severity of depressive symptoms (z score difference = -1.77), PTSD symptoms (-1.47), and depressive + PTSD symptoms (-2.29). Metacognitive biases improved after both targeted and entertainment training and was associated with reductions in depressive/PTSD symptom severity (r = -.41/-.42, respectively), led by the entertainment training group (r = -.54/-.46, respectively). These findings show that clinically significant severity of depressive/PTSD symptoms is associated with substantial negative global metacognitive biases and preliminarily suggests that cognitive training may improve these biases and depressive/PTSD symptom severity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Congruency and Emotional Valence Effects on Speech Production in Individuals with Parkinson's Disease.

Individuals with Parkinson's disease (PD) exhibit a variety of impairments in nonmotor symptoms including emotional processing and cognitive control that have implications for speech production. The present study sought to investigate whether impairments in cognitive processing in individuals with PD impact emotional sentence production as indicated by changes in speech rate. Thirty-six individuals (20 individuals with PD, 16 healthy controls) completed subtests 8A and 8B of the Florida Emotional Expressive Battery (FEEB) to elicit speech samples in five different emotional tones (happy, sad, angry, fear, and neutral). Sentences contained either semantically emotional or neutral information, resulting in conditions of congruency (same semantics-tone) and incongruency (different semantics-tone). Speech rate was impacted by the emotional tone of all participants. Individuals with PD demonstrated faster speech rates under conditions of conflicting semantic information than healthy older adults. Changes in speech rate under emotional conditions were not influenced by global measures of cognition or depression. The results of this study indicate that individuals with PD struggle to manage irrelevant information present during emotional speech production. Speech rate is a simple, easy-to-measure metric that may reflect cognitive processing impairments in PD.

Subjective cognitive decline and objective cognitive performance in older adults: A systematic review of longitudinal and cross-sectional studies.

Older adults with subjective cognitive decline (SCD) have a higher risk of developing future cognitive decline than those without SCD. However, the association between SCD and objective cognitive performance remains unclear. This PRISMA 2020-compliant systematic review aims to provide a qualitative assessment of the longitudinal and cross-sectional relationship between SCD and objective cognitive performance in different cognitive domains, in neuropsychologically healthy, community-dwelling older adults (average age of 55 or older). To identify pertinent studies, a comprehensive search was conducted from seven databases. The National Heart, Lung and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the quality of included studies. Inclusion criteria were met by 167 studies, which were full-text and published between 1 January 1982 and 16 May 2023 (inclusive) in the languages of English, French, or Spanish and presenting data on objective cognitive performance in older adults with SCD. Overall, we found that SCD was associated with poorer objective cognitive performance on measures of global cognition and memory longitudinally compared to non-SCD status, but this association was inconsistent in cross-sectional studies. This association became stronger with the use of continuous measures of SCD as opposed to dichotomous measures. Additionally, results highlight the known lack of consistency in SCD assessment among studies and comparatively small number of longitudinal studies in SCD research.

Linking the neural signature of response time variability to Alzheimer's disease pathology and cognitive functioning.

Promising evidence has suggested potential links between mind-wandering and Alzheimer's disease (AD). Yet, older adults with diagnosable neurocognitive disorders show reduced meta-awareness, thus questioning the validity of probe-assessed mind-wandering in older adults. In prior work, we employed response time variability as an objective, albeit indirect, marker of mind-wandering to identify patterns of functional connectivity that predicted mind-wandering. In the current study, we evaluated the association of this connectome-based, mind-wandering model with cerebral spinal fluid (CSF) p-tau/Aβ 42 ratio in 289 older adults from the Alzheimer's Disease NeuroImaging Initiative (ADNI). Moreover, we examined if this model was similarly associated with individual differences in composite measures of global cognition, episodic memory, and executive functioning. Edges from the high response time variability model were significantly associated with CSF p-tau/Aβ ratio. Furthermore, connectivity strength within edges associated with high response time variability was negatively associated with global cognition and episodic memory functioning. This study provides the first empirical support for a link between an objective neuromarker of mind-wandering and AD pathophysiology. Given the observed association between mind-wandering and cognitive functioning in older adults, interventions targeted at reducing mind-wandering, particularly before the onset of AD pathogenesis, may make a significant contribution to the prevention of AD-related cognitive decline.

Individual- and community-level social determinants of health are associated with cognition in older adults with focal epilepsy

ObjectiveEpilepsy is associated with significant health disparities, including access to specialized care and adverse outcomes that have been associated with several social determinants of health (SDOH). We sought to examine the relationship between individual- and community-level SDOH and cognitive outcomes in older adults with epilepsy. Materials and methodsWe collected clinical, SDOH, and neuropsychological data in 57 older adults with epilepsy. Individual-level SDOH included patient factors (quality of education, income, insurance, marital status) and early-life environmental factors (parental education and occupation, childhood employment). Neighborhood deprivation was measured with the Area Deprivation Index (ADI). Stepwise regressions were conducted to examine the independent contribution of individual-level SDOH to cognitive performance, and Spearman rho correlations were conducted to examine the relationship between ADI and cognitive performance. The SDOH profiles of patients who met the criteria for cognitive impairment were examined. ResultsAfter controlling for clinical variables, patient factors (public health insurance, poorer quality of education) and early-life environmental factors (lower mother’s education, lower father’s and mother’s occupational complexity, history of childhood employment) were significant predictors of lower performance on measures of global cognition, verbal learning and memory, processing speed, and executive function. Higher ADI values (greater disadvantage) were associated with lower scores on global cognitive measures, verbal learning and memory, and executive function. Patients who met criteria for cognitive impairment had, on average, a greater number of adverse SDOH, including lower household incomes and father’s education, and higher ADI values compared to those who were cognitively intact. ConclusionWe provide new evidence of the role of individual- and community-level SDOH on cognitive outcomes in older adults with epilepsy. This emerging literature highlights the need to examine SDOH beyond epilepsy-related clinical factors. These data could inform the development of interventions focused on increasing access to epilepsy care, education, and resources and promoting brain and cognitive health within the most at-risk communities.

Vietnamese Insights into Cognitive Aging Program (VIP): Objectives, study design, and cohort description.

There is a dearth of research on cognitive aging and dementia in Asian Americans, particularly in Vietnamese Americans, the fourth largest Asian subgroup in the United States. The Vietnamese Insights into Cognitive Aging Program (VIP) investigates early life adversity and war-related trauma and their associations with cognitive health in a community-based sample of older Vietnamese Americans in Northern California (i.e., Sacramento and Santa Clara counties). Baseline measurements include a comprehensive neuropsychological battery, including measures of global cognition along with executive function, semantic memory, and episodic memory. Data also include measures of functioning, early life adversity and trauma exposure, and psychosocial and traditional cardiovascular disease risk factors. Cognitive assessments will be repeated twice over the course of the data collection period, approximately 12- and 24- months post-baseline. Blood samples collected during Wave 2 will be assayed for biochemical risk factors. Baseline assessments were conducted from January 2022 to November 2023, with N=548 Vietnamese Americans; mean age ± SD was 73 ± 5.31 years and 55% of participants were women. There were significant differences in social factors by site, with Santa Clara participants having higher education (some college or higher: Sacramento, ≈25%; Santa Clara: ≈48%) and marginally higher incomes compared to Sacramento participants. A higher percentage of Santa Clara participants reported speaking English well or very well (24%) compared to Sacramento participants (13%), although the majority of the entire sample (81%) reported speaking some to no English (response options: not at all; some/a little bit; well/very well). This longitudinal study providea a unique opportunity to more fully delineate psychosocial factors that contribute to dementia disparities in diverse and under-engaged populations. Future work will examine cognition, the prevalence of mild cognitive impairment and dementia, and other health outcomes, while controlling for site differences in all analyses. Vietnamese Insights into Cognitive Aging Program (VIP) is a new study.VIP has detailed early life and health data on 548 older Vietnamese Americans.History of war and trauma may contribute to Alzheimer's disease and related dementias (ADRD)-related burden.VIP may provide insight into ADRD burden in other understudied groups.

Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease-related cognitive decline: Multi-site validation in the MarkVCID Consortium.

Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis. We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes. CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. The predefined hypothesis on the association between CVR and a global cognitive score was validated in three independent analysis sites, providing support for CVR as a biomarker in VCID. This study measured a novel functional index of small arteries referred to as cerebrovascular reactivity (CVR). CVR was positively associated with global cognition in older adults. This finding was observed in three independent cohorts at three sites. Our statistical analysis plan was predefined before beginning data collection.

Health and Financial Literacy and the Acquisition of COVID-19 Knowledge in Older Adults.

Knowledge about COVID-19 enters into many aspects of decision making, especially for older people who are at increased risk of severe disease or death. Yet little is known about the resources that supported older people's uptake of COVID-19 knowledge. Here, we hypothesized that higher pre-pandemic health and financial literacy was associated with higher COVID-19 knowledge. Participants were 434 community-based older people without dementia. COVID-19 knowledge was assessed via a 5-item measure, and health and financial literacy was assessed via a 32-item measure. In an ordinal regression model adjusted for age, gender, and education, higher literacy was associated with higher COVID-19 knowledge (p < .0001), and this association persisted after further adjusting for robust measures of global cognition or one of five specific cognitive domains (all p's ≤ .0001). These findings suggest that literacy plays a key role in supporting older people's acquisition of impactful knowledge in the real world.

A Longitudinal Study of the Effect of Memory on the Quality of life of European Adults and Older Adults

Among studies conceptualizing quality of life (QoL) as the subjective measure of one’s well-being, evidence suggests a link between cognitive impairment and diminished quality of life. However, the direction of the association is not clear, and most studies have employed a global measure of cognition, which can mask subtle domain-specific declines. In this study, we aim at examining the longitudinal associations between memory and QoL in a representative sample of adults and older adults in Europe and Israel, employing data from the Survey of Health, Ageing and Retirement in Europe (SHARE). The sample was composed by 56,616 respondents aged 50 or older at the beginning of the study period. A Parallel-Process Latent Growth Model (PP LGM) of memory and QoL conditioned on the effects of age, gender, educational level, physical inactivity, depressive symptomatology and social activity participation, was tested. Results displayed a trajectory of decline for both memory and QoL, with higher initial levels of memory associated with higher initial levels of QoL, and steeper decline in memory associated with steeper decline in QoL. Moreover, a positive effect of initial memory onto QoL trend over time was found, indicating that better memory is associated to better QoL in the future, but the opposite did not occur. Results also provide evidence of gender differences. All in all, this work found evidence supporting the longitudinal effect of memory on QoL, which may have consequences for intervention implementation, given that actions for alleviating age-related memory impairment could also have a positive impact onto older adults’ QoL.

Association between hippocampal microglia, AD and LATE-NC, and cognitive decline in older adults.

This study investigates the relationship between microglia inflammation in the hippocampus, brain pathologies, and cognitive decline. Participants underwent annual clinical evaluations and agreed to brain donation. Neuropathologic evaluations quantified microglial burden in the hippocampus, amyloid beta (Aβ), tau tangles, and limbic age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy neuropathologic changes (LATE-NC), and other common brain pathologies. Mixed-effect and linear regression models examined the association of microglia with a decline in global and domain-specific cognitive measures, and separately with brain pathologies. Path analyses estimated direct and indirect effects of microglia on global cognition. Hippocampal microglia were associated with a faster decline in global cognition, specifically in episodic memory, semantic memory, and perceptual speed. Tau tangles and LATE-NC were independently associated with microglia. Other pathologies, including Aβ, were not related. Regional hippocampal burden of tau tangles and TDP-43 accounted for half of the association of microglia with cognitive decline. Microglia inflammation in the hippocampus contributes to cognitive decline. Tau tangles and LATE-NC partially mediate this association.

Efficacy and safety of transcranial magnetic stimulation on cognition in mild cognitive impairment, Alzheimer's disease, Alzheimer's disease-related dementias, and other cognitive disorders: a systematic review and meta-analysis.

We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer's disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment. Systematic review, Meta-Analysis. We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023. RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included. Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423). The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer's Disease Assessment Scale-Cognitive Subscale (SMD = -0.96 [-1.32, -0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity. The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.

Vortioxetine Treatment for Depression in Patients with Prodromal vs Mild Alzheimer’s Disease: A Six-Month, Open-Label, Observational Study

BackgroundDepressive symptoms are common in Alzheimer disease (AD) from the prodromal stage. The benefits of antidepressants have been investigated in patients with AD dementia with mixed results.ObjectivesThis study aimed to compare the efficacy of vortioxetine in prodromal and mild-to-moderate AD patients with depression, and to assess the comparative effect on secondary measures, including behavioral disturbances, cognitive function, and activities of daily living.ParticipantsAll subjects with AD at a single-center dementia center underwent a standard evaluation with mini-mental state examination (MMSE), basic and instrumental activities of daily living (BADL and IADL), geriatric depression scale (CDS), neuropsychiatrie inventory (NPI), and clinical evaluation every six months.MeasurementsThe study specifically assessed patients on vortioxetine with available six-month follow-up data. The changes in CDS, NPI, MMSE, BADL/IADL at six months in the entire AD population and mild-to-moderate AD vs prodromal population were analyzed using repeated measure multivariate analyses. Linear regression analyses were implemented to evaluate baseline demographics and clinical characteristics associated with depressive and cognitive improvements at six months.ResultsOut of 680 AD patients, 115 were treated with vortioxetine, and 89 with six-month follow-up data were included in the analyses. A significant improvement at follow-up was observed for CDS, NPI total and sub score items (mood, anxiety, apathy, sleep disturbances, eating abnormalities). Both mild-to-moderate and prodromal AD showed a positive CDS response, whereas mild-to-moderate AD showed a better improvement on total NPI and apathy/nighttime behaviors subitems compared to prodromal AD. Higher baseline CDS score was the only variable associated with higher responses in linear regression analyses. MMSE showed a significant improvement at six months in the entire cohort, with a greater effect in prodromal vs mild-to-moderate AD. Cognitive improvement (i.e., MMSE changes) was associated with cognitive status at baseline but independent of the antidepressant/behavioral changes (i.e., GDS/NPI).ConclusionsOur results suggest that vortioxetine is highly tolerable and clinically effective in both prodromal and mild-to-moderate AD with depression. Patients with mild-to-moderate AD benefited more from a wide range of behavioral disturbances. The study also showed significant improvement in global cognitive measures, especially in prodromal AD subjects. Further studies are needed to investigate the independent beneficial effect of vortioxetine on depression and cognition in AD.

A multimodal group-based immersive virtual reality intervention for improving cognition and mental health in patients with post-covid-19 condition. A quasi-experimental design study.

Adults with Post-COVID-19 Condition (PCC) may show cognitive impairments in attention, processing speed, memory, and executive function. Multimodal programs that combine cognitive training, physical activity and emotional tasks, such as mindfulness-based interventions (MBIs), may offer a suitable alternative for improving PCC treatments. Immersive Virtual Reality (IVR) is a promising technology that can enhance traditional cognitive training, physical activity, and MBIs. The use of IVR technology may increase engagement with these interventions and potentially enhance the individual benefits of cognitive training, exercise and MBIs. The current study evaluated the impact of a multimodal IVR intervention, comparing this with a usual care intervention (control group), in order to assess changes in cognition and mental health in adults with PCC. We also aimed to assess user experience factors such as enjoyment, perceived improvement, and fatigue following each multimodal IVR session within the experimental group. Thirty-one participants with PCC symptoms were assigned to either the experimental group (IVR, n = 15) or the control group (usual care intervention, n = 16) in a quasi-experimental design study. The multimodal IVR intervention consisted of MBI, cognitive training and physical exercise and was delivered in a 60-min group session with 5 participants, twice a week, for 8 weeks (16 sessions in total). Measures of global cognition, attention, processing speed, verbal episodic memory and subjective memory complaints (primary measures), and depressive and anxiety symptoms and fatigue (secondary measures) were assessed at baseline and also after 8 weeks (post-intervention). Mixed between-group (group) and within-group (pre-post assessments) ANOVAs revealed significant group*time interactions in global cognition, simple attention, processing speed, memory and depressive symptoms, with large effect sizes (p < 0.05; partial η2 > 0.14). There was also a marginally significant group*time interaction for executive function (p = 0.05). Follow-up analyses comparing pre-and post-intervention outcomes for each group separately showed that the experimental group significantly improved in global cognition, processing speed, memory and depressive symptoms, while the control group showed no significant pre-post changes. Friedman tests showed a significant main effect of time (χ2(2) = 6.609, p = 0.04), with a gradual increase in enjoyment from the first, to the mid, and then to the final session. In addition, perceived improvement scores remained high throughout the intervention, and patient-reported fatigue levels did not fluctuate significantly throughout the intervention. To our knowledge, no previous research has combined cognitive training, physical exercise and MBI using an IVR paradigm in adults with PCC. Despite their inherent limitations, our findings mark a pioneering step toward improving cognition and mental health outcomes in PCC through the innovative use of new technology and multimodal approaches. This first study should be accompanied by more extensive, randomized clinical trials aimed at further exploring and refining these interventions.

Loneliness Predicts Progression of Frailty in Married and Widowed, but Not Unmarried Community Dwelling Older Adults.

Loneliness is highly prevalent among older adults and is associated with frailty. Most studies consider loneliness in isolation without consideration for structural and functional measures of social relationships - and longitudinal studies are scarce. This study examined longitudinal associations between loneliness and frailty and analyzed how structural and functional social measures influence these associations. Linear mixed effects models examined longitudinal associations between loneliness and frailty assessed with the frailty index (scale 0-100). Models were adjusted for baseline age, gender, education, depressive symptoms, global cognition, and structural (e.g., social network, marital status), and functional social measures (e.g., social, cognitive, and physical activity, and social support). Loneliness and frailty data from 1,931 older adults without dementia at baseline from the Rush Memory and Aging Project were examined (mean age 79.6 ± 7.7 years, 74.9% female). Baseline loneliness assessed by the de Jong Gierveld Loneliness Scale was the predictor of interest. Frailty increased significantly over a mean follow-up period of 4.6 years. Effects of loneliness on frailty were modified by marital status. Loneliness predicted an additional accumulation of 0.37 and 0.34 deficits on the frailty index per year in married and widowed individuals respectively, compared to those who were not lonely (married: p=0.009, CI 0.09, 0.64; widowed: p=0.005, CI 0.1, 0.58). Loneliness did not predict frailty progression in unmarried individuals. Loneliness predicts frailty progression, highlighting the importance of social determinants on physical health in aging.

IMMERSIVE VIRTUAL REALITY INTERVENTIONS FOR OLDER ADULTS: A SERIES OF META-ANALYSES

Abstract Many older adults desire to age in place, a term used to describe living independently versus transitioning to a residential care facility. Virtual reality (VR) has the potential to positively impact the functioning of older adults as an assessment or intervention to help compensate for lost or declining functions. VR captures a wide variety of technologies ranging from non-immersive to fully immersive, designed to give the user a feeling of presence. To date, VR interventions have been used with older adults including improving health outcomes, improving functional abilities, and for neuropsychological purposes. A handful of meta-analyses (M-As) attempt to summarize the overall effectiveness of VR interventions with older adults, but many contain methodological issues and cover the gamut of VR technology. The present M-A fills a gap in the literature by assessing the literature on immersive VR interventions for older adults. Sixteen articles met inclusion for meta-analysis, and 41 effect sizes (ES) were calculated. ES were grouped by category, neuropsychological, health/mental health, functional, and eight meta-analyses were performed with one exploratory analysis. Results revealed small, significant ES for VR interventions on measures of global cognition, simple attention tasks, executive functioning tasks, anxiety ratings, and pain ratings. Nonsignificant ES were found for stress ratings, gait speed, depression ratings, and TUG task (exploratory M-A). Continuing to develop affordable, safe interventions to assist with aging in place is important as the number of older adults continues to increase. Immersive VR is a promising avenue to continue exploring to better assist the aging population.