Alzheimer's Disease Plasma Biomarkers Distinguish Clinical Diagnostic Groups in Memory Clinic Patients

INTRODUCTION: Several recent research studies show high performance of blood biomarkers to identify Alzheimer's disease also in the pre-dementia mild cognitive impairment (MCI) stage, but data from the routine clinical care memory clinic setting are needed. METHODS: We examined plasma samples of 144 memory clinic patients, including dementia of Alzheimer type (DAT, n = 54), MCI (n = 57), and subjective cognitive decline (SCD, n = 33), who either presented as self-referrals or were referred by general practitioners or neurologists or psychiatrists. The plasma biomarkers, amyloid-beta42 (Aß42), amyloid-beta40 (Aß40), phospho-Tau181 (pTau181), total-tau (tTau), and neurofilament light (NFL), as well as different ratios, were measured using the ultrasensitive single molecule array (Simoa) immunoassay technology. Statistical analysis including Kruskal-Wallis test, linear regression, and receiver operating characteristics analyses was performed. RESULTS: Of the single markers, we observed statistically significant group effects of pTau181 (H(2) = 34.43, p < 0.001) and NFL (H(2) = 27.66, p < 0.001). All individual group comparisons of pTau181 were significant, while the contrast of SCD versus MCI for NFL was not significant. In addition, the ratios of Aß42/Aß40 (H(2) = 7.50, p = 0.02) and pTau181/Aß42 (H(2) = 25.26, p < 0.001) showed significant group effects with significant difference between all groups for pTau181/Aß42 and an SCD versus MCI difference for Aß42/Aß40. PTau181 showed the highest area under the curve of 0.85 for the discrimination of SCD and DAT with a sensitivity of 80% and a specificity of 79% at a cut-off of 12.2 pg/mL. Age influenced Aß42, Aß40, and NFL concentrations. CONCLUSION: Plasma pTau181 and NFL, as well as the ratios Aß42/Aß40 and pTau181/Aß42, are biomarkers, which can differentiate diagnostic groups in a memory clinic setting outside of research studies

Effects of Meditation Training and Non-Native Language Training on Cognition in Older Adults: A Secondary Analysis of a Randomized Clinical Trial

IMPORTANCE: Nonpharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults. OBJECTIVE: To investigate the effects of 18 months' meditation training and 18 months' non-native language training on cognition in older adults. DESIGN, SETTING, AND PARTICIPANTS: This study was a secondary analysis of the Age-Well trial, an 18-month, observer-masked, randomized clinical trial with 3 parallel arms. Eligible participants were community-dwelling adults aged 65 years and older residing in Caen, France. Participants were enrolled from November 24, 2016, to March 5, 2018, and randomly assigned (1:1:1) to meditation training, non-native language (English) training, or no intervention arms. Final follow-up was completed on February 6, 2020. Data were analyzed between December 2021 and November 2022. INTERVENTIONS: The 18-month meditation and non-native language training interventions were structurally equivalent and included 2-hour weekly group sessions, daily home practice of 20 minutes or longer, and 1 day of more intensive home practice. The no intervention group was instructed not to change their habits and to continue living as usual. MAIN OUTCOMES AND MEASURES: Cognition (a prespecified secondary outcome of the Age-Well trial) was assessed preintervention and postintervention via the Preclinical Alzheimer Cognitive Composite 5 (PACC5), and composites assessing episodic memory, executive function, and attention. RESULTS: Among 137 randomized participants, 2 were excluded for not meeting eligibility criteria, leaving 135 (mean [SD] age, 69.3 [3.8] years; 83 female [61%]) eligible for analysis. One participant among the remaining 135 did not complete the trial. In adjusted mixed effects models, no interaction effects were observed between visit and group for PACC5 (F2,131.39 = 2.58; P = .08), episodic memory (F2,131.60 = 2.34; P = .10), executive function (F2,131.26 = 0.89; P = .41), or attention (F2,131.20 = 0.34; P = .79). Results remained substantively unchanged across sensitivity and exploratory analyses. CONCLUSIONS AND RELEVANCE: In this secondary analysis of an 18-month randomized trial, meditation and non-native language training did not confer salutary cognitive effects. Although further analyses are needed to explore the effects of these interventions on other relevant outcomes related to aging and well-being, these findings did not support the use of these interventions for enhancing cognition in cognitively healthy older adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02977819

Effects of a mindfulness-based versus a health self-management intervention on objective cognitive performance in older adults with subjective cognitive decline (SCD): a secondary analysis of the SCD-Well randomized controlled trial.

peer reviewedBACKGROUND: Older individuals with subjective cognitive decline (SCD) perceive that their cognition has declined but do not show objective impairment on neuropsychological tests. Individuals with SCD are at elevated risk of objective cognitive decline and incident dementia. Non-pharmacological interventions (including mindfulness-based and health self-management approaches) are a potential strategy to maintain or improve cognition in SCD, which may ultimately reduce dementia risk. METHODS: This study utilized data from the SCD-Well randomized controlled trial. One hundred forty-seven older adults with SCD (MAge = 72.7 years; 64% female) were recruited from memory clinics in four European countries and randomized to one of two group-based, 8-week interventions: a Caring Mindfulness-based Approach for Seniors (CMBAS) or a health self-management program (HSMP). Participants were assessed at baseline, post-intervention (week 8), and at 6-month follow-up (week 24) using a range of cognitive tests. From these tests, three composites were derived-an "abridged" Preclinical Alzheimer's Cognitive Composite 5 (PACC5Abridged), an attention composite, and an executive function composite. Both per-protocol and intention-to-treat analyses were performed. Linear mixed models evaluated the change in outcomes between and within arms and adjusted for covariates and cognitive retest effects. Sensitivity models repeated the per-protocol analyses for participants who attended ≥ 4 intervention sessions. RESULTS: Across all cognitive composites, there were no significant time-by-trial arm interactions and no measurable cognitive retest effects; sensitivity analyses supported these results. Improvements, however, were observed within both trial arms on the PACC5Abridged from baseline to follow-up (Δ [95% confidence interval]: CMBAS = 0.34 [0.19, 0.48]; HSMP = 0.30 [0.15, 0.44]). There was weaker evidence of an improvement in attention but no effects on executive function. CONCLUSIONS: Two non-pharmacological interventions conferred small, non-differing improvements to a global cognitive composite sensitive to amyloid-beta-related decline. There was weaker evidence of an effect on attention, and no evidence of an effect on executive function. Importantly, observed improvements were maintained beyond the end of the interventions. Improving cognition is an important step toward dementia prevention, and future research is needed to delineate the mechanisms of action of these interventions and to utilize clinical endpoints (i.e., progression to mild cognitive impairment or dementia). TRIAL REGISTRATION: ClinicalTrials.gov, NCT03005652

The Effect of Mindfulness-based Programs on Cognitive Function in Adults: A Systematic Review and Meta-analysis.

peer reviewedMindfulness-based programs (MBPs) are increasingly utilized to improve mental health. Interest in the putative effects of MBPs on cognitive function is also growing. This is the first meta-analysis of objective cognitive outcomes across multiple domains from randomized MBP studies of adults. Seven databases were systematically searched to January 2020. Fifty-six unique studies (n = 2,931) were included, of which 45 (n = 2,238) were synthesized using robust variance estimation meta-analysis. Meta-regression and subgroup analyses evaluated moderators. Pooling data across cognitive domains, the summary effect size for all studies favored MBPs over comparators and was small in magnitude (g = 0.15; [0.05, 0.24]). Across subgroup analyses of individual cognitive domains/subdomains, MBPs outperformed comparators for executive function (g = 0.15; [0.02, 0.27]) and working memory outcomes (g = 0.23; [0.11, 0.36]) only. Subgroup analyses identified significant effects for studies of non-clinical samples, as well as for adults aged over 60. Across all studies, MBPs outperformed inactive, but not active comparators. Limitations include the primarily unclear within-study risk of bias (only a minority of studies were considered low risk), and that statistical constraints rendered some p-values unreliable. Together, results partially corroborate the hypothesized link between mindfulness practices and cognitive performance. This review was registered with PROSPERO [CRD42018100904]

A Network Perspective on Neuropsychiatric and Cognitive Symptoms of the Post-COVID Syndrome

Many patients that were infected with SARS-CoV-2 experience cognitive and affective symptoms weeks and months after their acute COVID-19 disease, even when acute symptoms were mild to moderate. For these patients, purely neurological explanations are struggling to explain the development and maintenance of the great variety of neuropsychiatric and cognitive symptoms occurring after COVID-19. We provide a psychological perspective based on the network theory of mental disorders as an added explanation that does not displace neurological mechanism but rather complements them. We suggest viewing the SARS-CoV-2 infection as a trigger that first activates nodes in a causally connected network of neuropsychiatric and cognitive symptoms. In the following, activation will spread throughout the network that will get in a self-sustaining stable and dysfunctional state manifesting in ongoing symptoms known as post-COVID-19 syndrome. The network perspective allows to generalize explanations for persistent neuropsychiatric and cognitive symptoms to patients that experienced mild or moderate acute courses of COVID-19, but also to similar phenomena following other viral infections. In addition, it could explain why some symptoms did not occur during acute COVID-19, but develop weeks or months after it. This network perspective shifts the focus from viewing persistent symptoms as a continuation of COVID-19 to acknowledging it as a complex syndrome that indeed originates from the disease but fully unfolds after it (post-COVID). To test the presented network perspective, we will need extensive cross-sectional as well as longitudinal data on cognitive and neuropsychiatric symptoms in post-COVID patients

Social Cognition in Patients with Amnestic Mild Cognitive Impairment and Mild Dementia of the Alzheimer Type

Background: Social cognition (SC) is a core criterion for neurocognitive disorders. However, findings in patients with amnestic mild cognitive impairment (aMCI) and dementia of the Alzheimer type (DAT) are inconsistent. Objective: We report assessments of emotion recognition (ER), affective and cognitive theory of mind (ToM) in young (YC) and older controls (OC) compared to aMCI and DAT. Methods: 28 aMCI, 30 DAT, 30 YC, and 29 OC received tests of SC and a comprehensive neuropsychological assessment. Analysis of covariance was used to determine group differences. Multiple regression models were applied to identify predictors for each SC task. Results: In controls, OC performed worse in ER and both ToM tasks compared to YC except for one subtest. No significant differences were found between OC and patients concerning ER and affective ToM. In cognitive ToM, differences between OC and patients depended on content and cognitive load with significant impairment in DAT compared to OC. A cognitive composite score predicted SC in OC, but not in patients. Associations of SC with single cognitive domains were found in all groups with language and complex attention as best predictors. Not all variance of SC performance was explained by variance in cognitive domains. Conclusion: Lower performance on SC tasks in OC versus YC was confirmed, although not all tasks were equally affected. With progressive cognitive impairment, cognitive ToM is more impaired than ER or affective ToM. SC seems to be at least partly independent of other cognitive domains, justifying its inclusion in batteries for dementia diagnostic

Multidomain cognitive impairment in non-hospitalized patients with the post-COVID-19 syndrome: results from a prospective monocentric cohort

Background A fraction of patients with asymptomatic to mild/moderate acute COVID-19 disease report cognitive deficits as part of the post-COVID-19 syndrome. This study aimed to assess the neuropsychological profile of these patients. Methods Assessment at baseline (three months or more following acute COVID-19) of a monocentric prospective cohort of patients with post-COVID-19 syndrome. Multidomain neuropsychological tests were performed, and questionnaires on depression, anxiety, fatigue, sleep, and general health status were administered. Results Of the 58 patients screened, six were excluded due to possible alternative causes of cognitive impairment (major depression, neurodegenerative disease). Of the remaining 52 individuals, only one had a below-threshold screening result on Mini-Mental State Examination, and 13 scored below the cut-off on Montreal Cognitive Assessment. Extended neuropsychological testing revealed a neurocognitive disorder (NCD) in 31 (59.6%) participants with minor NCD in the majority of cases (n = 26). In patients with NCD, the cognitive domains learning/memory and executive functions were impaired in 60.7%, complex attention in 51.6%, language in 35.5%, and perceptual-motor function in 29.0%. Cognitive profiles were associated with daytime sleepiness but not with depression, anxiety, sleep quality, total general health status, or fatigue. Conclusion Neurocognitive impairment can be confirmed in around 60% of individuals with self-reported deficits as part of post-COVID-19 syndrome following a mild acute COVID-19 disease course. Notably, screening tests cannot reliably detect this dysfunction. Standard psychiatric assessments showed no association with cognitive profiles. Longitudinal studies are needed to further evaluate the course of neurocognitive deficits and clarify pathophysiology

Effects of Meditation Training and Non-Native Language Training on Cognition in Older Adults: A Secondary Analysis of a Randomized Clinical Trial.

peer reviewedIMPORTANCE: Nonpharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults. OBJECTIVE: To investigate the effects of 18 months' meditation training and 18 months' non-native language training on cognition in older adults. DESIGN, SETTING, AND PARTICIPANTS: This study was a secondary analysis of the Age-Well trial, an 18-month, observer-masked, randomized clinical trial with 3 parallel arms. Eligible participants were community-dwelling adults aged 65 years and older residing in Caen, France. Participants were enrolled from November 24, 2016, to March 5, 2018, and randomly assigned (1:1:1) to meditation training, non-native language (English) training, or no intervention arms. Final follow-up was completed on February 6, 2020. Data were analyzed between December 2021 and November 2022. INTERVENTIONS: The 18-month meditation and non-native language training interventions were structurally equivalent and included 2-hour weekly group sessions, daily home practice of 20 minutes or longer, and 1 day of more intensive home practice. The no intervention group was instructed not to change their habits and to continue living as usual. MAIN OUTCOMES AND MEASURES: Cognition (a prespecified secondary outcome of the Age-Well trial) was assessed preintervention and postintervention via the Preclinical Alzheimer Cognitive Composite 5 (PACC5), and composites assessing episodic memory, executive function, and attention. RESULTS: Among 137 randomized participants, 2 were excluded for not meeting eligibility criteria, leaving 135 (mean [SD] age, 69.3 [3.8] years; 83 female [61%]) eligible for analysis. One participant among the remaining 135 did not complete the trial. In adjusted mixed effects models, no interaction effects were observed between visit and group for PACC5 (F2,131.39 = 2.58; P = .08), episodic memory (F2,131.60 = 2.34; P = .10), executive function (F2,131.26 = 0.89; P = .41), or attention (F2,131.20 = 0.34; P = .79). Results remained substantively unchanged across sensitivity and exploratory analyses. CONCLUSIONS AND RELEVANCE: In this secondary analysis of an 18-month randomized trial, meditation and non-native language training did not confer salutary cognitive effects. Although further analyses are needed to explore the effects of these interventions on other relevant outcomes related to aging and well-being, these findings did not support the use of these interventions for enhancing cognition in cognitively healthy older adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02977819.Investigating the impact of meditation training on mental health and wellbeing in the ageing populatio

Alzheimers Dement

Introduction: Subjectively experienced cognitive decline in older adults is an indicator of increased risk for dementia and is also associated with increased levels of anxiety symptoms. As anxiety is itself emerging as a risk factor for cognitive decline and dementia, the primary question of the present study is whether an 8-week mindfulness-based intervention can significantly reduce anxiety symptoms in patients with subjective cognitive decline (SCD). The secondary questions pertain to whether such changes extend to other domains of psychological, social, and biological functioning (including cognition, self-regulation, lifestyle, well-being and quality of life, sleep, and selected blood-based biomarkers) associated with mental health, older age, and risk for dementia. Methods: SCD-Well is a multicenter, observer-blinded, randomized, controlled, superiority trial, which is part of the Horizon 2020 European Union-funded "Medit-Ageing" project. SCD-Well compares an 8-week mindfulness- and compassion-based intervention specifically adapted for older adults with SCD with a validated 8-week health education program. Participants were recruited from memory clinics in four European sites (Cologne, Germany; London, United Kingdom; Barcelona, Spain; and Lyon, France) and randomized with a 1:1 allocation, stratified by site. Results: The primary outcome, change in anxiety symptoms, and secondary outcomes reflecting psychological, cognitive, social, and biological functioning are assessed at baseline, postintervention, and 4 months after the end of the intervention. Discussion: The study will provide evidence on whether a mindfulness-based intervention can effect changes in anxiety and other risk factors for cognitive decline and dementia in older adults with SCD and will inform the establishment of intervention strategies targeted at improving mental health in older adults