The Associations Between Neuropsychiatric Symptoms and Cognition in People with Dementia: A Systematic Review and Meta-Analysis.

Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship between NPS and cognitive impairment, but data is still limited. This study aimed to investigate the specific associations between NPS and cognition in people with dementia. MEDLINE, EMBASE and PsycINFO were searched for published, peer-reviewed studies of associations between at least one NPS and one cognitive ability in people with dementia. The quality of the studies was assessed with the NIH National Heart, Lung and Blood Institute's quality assessment tools. A meta-analysis was conducted using Robumeta package for R. Ninety studies were included. We found significant associations between NPS, global cognition and cognitive domains, e.g. apathy was associated with global cognitive and memory impairment; dysphoria was associated with worse attention; delusions with executive dysfunction. Increased NPS in people with dementia are associated with worse cognitive performance. There were few studies looking at associations between some neuropsychiatric clusters and cognitive abilities, and there was little research on causal relationships. Our review was limited by the inclusion of studies that reported associations in specific formats, and most included people with a diagnosis of Alzheimer's disease (AD). However, given the large number of studies, this is unlikely to have biased results. More research is needed that includes diverse people with different dementia syndromes. Registration: PROSPERO 2020 CRD42020165565.

Cognitive rehabilitation for people with mild to moderate dementia.

BACKGROUND: Cognitive impairments affect functional ability in people with dementia. Cognitive rehabilitation (CR) is a personalised, solution-focused approach that aims to enable people with mild-to-moderate dementia to manage everyday activities and maintain as much independence as possible. OBJECTIVES: To evaluate the effects of CR on everyday functioning and other outcomes for people with mild-to-moderate dementia, and on outcomes for care partners. To identify and explore factors that may be associated with the efficacy of CR. SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group Specialised Register, which contains records from MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, and other clinical trial databases, and grey literature sources. The most recent search was completed on 19 October 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing CR with control conditions and reporting relevant outcomes for the person with dementia and/or the care partner. DATA COLLECTION AND ANALYSIS: We extracted relevant data from published manuscripts and contacted trial authors if necessary. Within each of the comparisons, we pooled data for each outcome of interest and conducted inverse-variance, random-effects meta-analyses. We evaluated the certainty of the evidence using GRADEpro GDT. MAIN RESULTS: We identified six eligible RCTs published in English between 2010 and 2022, which together included 1702 participants. The mean age of participants ranged from 76 to 80 and the proportion of male participants was between 29.4% and 79.3%. Most participants, in the studies where the type of dementia was reported, had a diagnosis of Alzheimer's disease (AD; n = 1002, 58.9% of the whole sample, 81.2% of the participants for whom the specific diagnosis was reported). Risk of bias in the individual studies was relatively low. The exception was a high risk of bias in relation to blinding of participants and practitioners, which is not usually feasible with psychosocial interventions.  Our primary outcome of everyday functioning was operationalised in the included studies as goal attainment in relation to activities targeted in the intervention. For our main comparison of CR with usual care, we pooled data for goal attainment evaluated from three perspectives (self-rating of performance, informant rating of performance, and self-rating of satisfaction with performance) at end of treatment and at medium-term follow-up (3 to 12 months). We could also pool data at these time points for 20 and 19 secondary outcomes respectively. The review findings were strongly driven by one large, high-quality RCT.  We found high-certainty evidence of large positive effects of CR on all three primary outcome perspectives at the end of treatment: participant self-ratings of goal attainment (standardised mean difference (SMD) 1.46, 95% confidence interval (CI) 1.26 to 1.66; I2 = 0%; 3 RCTs, 501 participants), informant ratings of goal attainment (SMD 1.61, 95% CI 1.01 to 2.21; I2 = 41%; 3 RCTs, 476 participants), and self-ratings of satisfaction with goal attainment (SMD 1.31, 95% CI 1.09 to 1.54; I2 = 5%; 3 RCTs, 501 participants), relative to an inactive control condition. At medium-term follow-up, we found high-certainty evidence showing a large positive effect of CR on all three primary outcome perspectives: participant self-ratings of goal attainment (SMD 1.46, 95% CI 1.25 to 1.68; I2 = 0%; 2 RCTs, 432 participants), informant ratings of goal attainment (SMD 1.25, 95% CI 0.78 to 1.72; I2 = 29%; 3 RCTs, 446 participants), and self-ratings of satisfaction with goal attainment (SMD 1.19, 95% CI 0.73 to 1.66; I2 = 28%; 2 RCTs, 432 participants), relative to an inactive control condition. For participants at the end of treatment we found high-certainty evidence showing a small positive effect of CR on self-efficacy (2 RCTs, 456 participants) and immediate recall (2 RCTs, 459 participants). For participants at medium-term follow-up we found moderate-certainty evidence showing a small positive effect of CR on auditory selective attention (2 RCTs, 386 participants), and a small negative effect on general functional ability (3 RCTs, 673 participants), and we found low-certainty evidence showing a small positive effect on sustained attention (2 RCTs, 413 participants), and a small negative effect on memory (2 RCTs, 51 participants) and anxiety (3 RCTs, 455 participants).  We found moderate- and low-certainty evidence indicating that at the end of treatment CR had negligible effects on participant anxiety, quality of life, sustained attention, memory, delayed recall, and general functional ability, and at medium-term follow-up on participant self-efficacy, depression, quality of life, immediate recall, and verbal fluency. For care partners at the end of treatment we found low-certainty evidence showing a small positive effect on environmental aspects of quality of life (3 RCTs, 465 care partners), and small negative effects of CR on level of depression (2 RCTs, 32 care partners) and on psychological wellbeing (2 RCTs, 388 care partners).  For care partners at medium-term follow-up we found high-certainty evidence showing a small positive effect of CR on social aspects of quality of life (3 RCTs, 436 care partners) and moderate-certainty evidence showing a small positive effect on psychological aspects of quality of life (3 RCTs, 437 care partners). We found moderate- and low-certainty evidence at the end of treatment that CR had negligible effects on care partners' physical health, psychological and social aspects of quality of life, and stress, and at medium-term follow-up for the physical health aspect of care partners' quality of life and psychological wellbeing. AUTHORS' CONCLUSIONS: CR is helpful in enabling people with mild or moderate dementia to improve their ability to manage the everyday activities targeted in the intervention. Confidence in these findings could be strengthened if more high-quality studies contributed to the observed effects. The available evidence suggests that CR can form a valuable part of a clinical toolkit to assist people with dementia in overcoming some of the everyday barriers imposed by cognitive and functional difficulties. Future research, including process evaluation studies, could help identify avenues to maximise CR effects and achieve wider impacts on functional ability and wellbeing.

ANTECEDENTES: El deterioro cognitivo afecta la capacidad funcional de las personas con demencia. La rehabilitación cognitiva (RC) es un enfoque personalizado y centrado en soluciones que pretende que las personas con demencia de leve a moderada puedan realizar las actividades cotidianas y mantener la mayor independencia posible. OBJETIVOS: Evaluar los efectos de la RC en la funcionalidad cotidiana y otros desenlaces de las personas con demencia leve a moderada, así como en los desenlaces de los cuidadores. Identificar y explorar los factores que pueden estar asociados con la eficacia de la RC. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en el Registro especializado del Grupo Cochrane de Demencia y trastornos cognitivos (Cochrane Dementia and Cognitive Improvement Group), que contiene registros de MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS y otras bases de datos de ensayos clínicos, y fuentes de literatura gris. La búsqueda más reciente se completó el 19 de noviembre de 2022. CRITERIOS DE SELECCIÓN: Se incluyeron los ensayos controlados aleatorizados (ECA) que compararon la RC con condiciones control e informaron desenlaces relevantes para la persona con demencia y el cuidador. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se extrajeron los datos pertinentes de los manuscritos publicados y se estableció contacto con los autores de los ensayos de ser necesario. Dentro de cada una de las comparaciones, se agruparon los datos de cada desenlace de interés y se realizaron metanálisis de efectos aleatorios por la inversa de la varianza. La certeza de la evidencia se evaluó mediante el método GRADE. RESULTADOS PRINCIPALES: Se identificaron seis ECA elegibles publicados en inglés entre 2010 y 2022, que en conjunto incluyeron 1702 participantes. La media de edad de los participantes varió de 76 a 80 años, y la proporción de participantes masculinos varió del 29,4% al 79,3%. La mayoría de los participantes, de los estudios en los que se informó el tipo de demencia, tenían un diagnóstico de enfermedad de Alzheimer (EA; n = 1002, 58,9% de toda la muestra, 81,2% de los participantes en los que se informó el diagnóstico específico). El riesgo de sesgo en los estudios individuales fue relativamente bajo. La excepción fue un alto riesgo de sesgo en relación con el cegamiento de los participantes y los profesionales, que no suele ser factible con las intervenciones psicosociales.  El desenlace principal de la funcionalidad cotidiana se operacionalizó en los estudios incluidos como el logro de objetivos en relación con las actividades abordadas en la intervención. Para la comparación principal de la RC con la atención habitual, se agruparon los datos del logro de los objetivos evaluados desde tres perspectivas (autoevaluación del desempeño, valoración de los informantes sobre el desempeño y autoevaluación de la satisfacción con el desempeño) al final del tratamiento y en el seguimiento a medio plazo (de tres a 12 meses). También fue posible agrupar los datos en estos puntos temporales de 20 y 19 desenlaces secundarios respectivamente. Los resultados de la revisión dependieron fuertemente de un ECA grande y de calidad alta.  Se encontró evidencia de certeza alta de grandes efectos positivos de la RC en los tres desenlaces principales al final del tratamiento: autoevaluaciones de los participantes sobre el logro de los objetivos (diferencia de medias estandarizada [DME] 1,46; intervalo de confianza [IC] del 95%: 1,26 a 1,66; I 2 = 0%; tres ECA, 501 participantes), valoraciones de los informantes sobre el logro de los objetivos (DME 1,61; IC del 95%: 1,01 a 2,21; I 2 = 41%; tres ECA, 476 participantes) y autoevaluaciones de la satisfacción con el logro de los objetivos (DME 1,31; IC del 95%: 1,09 a 1,54; I 2 = 5%; tres ECA, 501 participantes), en relación con una condición control inactiva. En el seguimiento a medio plazo se encontró evidencia de certeza alta que mostró un gran efecto positivo de la RC sobre las tres perspectivas de desenlaces principales: autoevaluaciones de los participantes sobre el logro de los objetivos (DME 1,46; IC del 95%: 1,25 a 1,68; I 2 = 0%; dos ECA, 432 participantes), valoraciones de los informantes sobre el logro de los objetivos (DME 1,25; IC del 95%: 0,78 a 1,72; I 2 = 29%; tres ECA, 446 participantes) y autoevaluaciones de la satisfacción con el logro de los objetivos (DME 1,19; IC del 95%: 0,73 a 1,66; I 2 = 28%; dos ECA, 432 participantes), en relación con una condición control inactiva. Con respecto a los participantes, al final del tratamiento se encontró evidencia de certeza alta que muestra un pequeño efecto positivo de la RC sobre la autoeficacia (dos ECA, 456 participantes) y el recuerdo inmediato (dos ECA, 459 participantes). También en los participantes, en el seguimiento a medio plazo se encontró evidencia de certeza moderada que mostró un pequeño efecto positivo de la RC sobre la atención auditiva selectiva (dos ECA, 386 participantes) y un pequeño efecto negativo sobre la capacidad funcional general (tres ECA, 673 participantes), además se encontró evidencia de certeza baja que mostró un pequeño efecto positivo sobre la atención sostenida (dos ECA, 413 participantes) y un pequeño efecto negativo sobre la memoria (dos ECA, 51 participantes) y la ansiedad (tres ECA, 455 participantes).  Se encontró evidencia de certeza moderada y baja que indicó que al final del tratamiento la RC tuvo efectos insignificantes sobre la ansiedad, la calidad de vida, la atención sostenida, la memoria, el recuerdo retardado y la capacidad funcional general de los participantes, y en el seguimiento a medio plazo sobre la autoeficacia, la depresión, la calidad de vida, el recuerdo inmediato y la fluidez verbal de los participantes. En el caso de los cuidadores, al final del tratamiento se encontró evidencia de certeza baja que mostró un pequeño efecto positivo sobre los aspectos ambientales de la calidad de vida (tres ECA, 465 cuidadores), y pequeños efectos negativos de la RC sobre el nivel de depresión (dos ECA, 32 cuidadores) y sobre el bienestar psicológico (dos ECA, 388 cuidadores).  También en los cuidadores, en el seguimiento a medio plazo se encontró evidencia de certeza alta que mostró un pequeño efecto positivo de la RC sobre los aspectos sociales de la calidad de vida (tres ECA, 436 cuidadores) y evidencia de certeza moderada que mostró un pequeño efecto positivo sobre los aspectos psicológicos de la calidad de vida (tres ECA, 437 cuidadores). Se encontró evidencia de certeza moderada y baja al final del tratamiento de que la RC tenía efectos insignificantes sobre la salud física de los cuidadores, los aspectos psicológicos y sociales de la calidad de vida y el estrés, así como en el seguimiento a medio plazo en el aspecto de la salud física de la calidad de vida de los cuidadores y el bienestar psicológico. CONCLUSIONES DE LOS AUTORES: La RC ayuda a las personas con demencia leve o moderada a mejorar su capacidad para realizar las actividades cotidianas objeto de la intervención. La confianza en estos resultados se podría reforzar si más estudios de calidad alta contribuyeran a los efectos observados. La evidencia disponible indica que la RC podría constituir una parte valiosa de un conjunto de herramientas clínicas para ayudar a las personas con demencia a superar algunas de las barreras cotidianas impuestas por las dificultades cognitivas y funcionales. Los estudios de investigación futuros, incluidos los estudios de evaluación de procesos, podrían ayudar a identificar vías para maximizar los efectos de la RC y lograr repercusiones más amplias en la capacidad funcional y el bienestar.

Including ethnic minorities in dementia research: Recommendations from a scoping review.

Introduction: Ethnicity influences dementia etiology, prognosis, and treatment, while culture shapes help-seeking and care. Despite increasing population diversity in high-income settlement countries, ethnic minorities remain underrepresented in dementia research. We investigated approaches to enhance the recruitment, and consistent collection and analysis of variables relevant to, ethnic minorities in dementia studies to make recommendations for consistent practice in dementia research. Methods: We did a scoping review, searching Embase, PsycINFO, Medline, CENTRAL, and CINAHL between January 1, 2010 and January 7, 2020. Dementia clinical and cohort studies that actively recruited ethnic minorities in high-income countries were included. A steering group of experts developed criteria through which high-quality studies were identified. Results: Sixty-six articles were retrieved (51 observational; 15 experimental). Use of interpreters and translators (n = 17) was the most common method to facilitate participant recruitment. Race and ethnicity (n = 59) were the most common variables collected, followed by information on native language (n = 14), country of birth (n = 9), and length of time in country of settlement (n = 8). Thirty-three studies translated or used a culturally validated instrument. Twenty-three articles conducted subgroup analyses based on ethnicity. Six high-quality studies facilitated inclusion through community engagement, collected information on multiple aspects of ethnic diversity, and adjusted/substratified to analyze the impact of ethnicity on dementia. Discussion: We make recommendations for consistent recruitment, collection, and reporting of variables relating to ethnic and cultural diversity in dementia research.

CogTale: an online platform for the evaluation, synthesis, and dissemination of evidence from cognitive interventions studies.

Systematic reviews and meta-analyses are critical in health-related decision-making, and are considered the gold standard in research synthesis methods. However, with new trials being regularly published and with the development of increasingly rigorous standards of data synthesis, systematic reviews often require much expertise and long periods of time to be completed. Automation of some of the steps of evidence synthesis productions is a promising improvement in the field, capable of reducing the time and costs associated with the process.This article describes the development and main characteristics of a novel online repository of cognitive intervention studies entitled Cognitive Treatments Article Library and Evaluation (CogTale). The platform is currently in a Beta Release phase, as it is still under development. However, it already contains over 70 studies, and the CogTale team is continuously coding and uploading new studies into the repository. Key features include advanced search options, the capability to generate meta-analyses, and an up-to-date display of relevant published studies.

Cognition-Oriented Treatments for Older Adults: a Systematic Overview of Systematic Reviews.

Cognition-oriented treatments - commonly categorized as cognitive training, cognitive rehabilitation and cognitive stimulation - are promising approaches for the prevention of cognitive and functional decline in older adults. We conducted a systematic overview of meta-analyses investigating the efficacy of cognition-oriented treatments on cognitive and non-cognitive outcomes in older adults with or without cognitive impairment. Review quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR). We identified 51 eligible reviews, 46 of which were included in the quantitative synthesis. The confidence ratings were "moderate" for 9 (20%), "low" for 13 (28%) and "critically low" for 24 (52%) of the 46 reviews. While most reviews provided pooled effect estimates for objective cognition, non-cognitive outcomes of potential relevance were more sparsely reported. The mean effect estimate on cognition was small for cognitive training in healthy older adults (mean Hedges' g = 0.32, range 0.13-0.64, 19 reviews), mild cognitive impairment (mean Hedges' g = 0.40, range 0.32-0.60, five reviews), and dementia (mean Hedges' g = 0.38, range 0.09-1.16, seven reviews), and small for cognitive stimulation in dementia (mean Hedges' g = 0.36, range 0.26-0.44, five reviews). Meta-regression revealed that higher AMSTAR score was associated with larger effect estimates for cognitive outcomes. The available evidence supports the efficacy of cognition-oriented treatments improving cognitive performance in older adults. The extent to which such effects are of clinical value remains unclear, due to the scarcity of high-quality evidence and heterogeneity in reported findings. An important avenue for future trials is to include relevant non-cognitive outcomes in a more consistent way and, for meta-analyses in the field, there is a need for better adherence to methodological standards. PROSPERO registration number: CRD42018084490.

Cognitive training for people with mild to moderate dementia.

BACKGROUND: Cognitive impairment, a defining feature of dementia, plays an important role in the compromised functional independence that characterises the condition. Cognitive training (CT) is an approach that uses guided practice on structured tasks with the direct aim of improving or maintaining cognitive abilities. OBJECTIVES: • To assess effects of CT on cognitive and non-cognitive outcomes for people with mild to moderate dementia and their caregivers.• To compare effects of CT with those of other non-pharmacological interventions, including cognitive stimulation or rehabilitation, for people with mild to moderate dementia and their caregivers.• To identify and explore factors related to intervention and trial design that may be associated with the efficacy of CT for people with mild to moderate dementia and their caregivers. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialised Register, on 5 July 2018. ALOIS contains records of clinical trials identified through monthly searches of several major healthcare databases and numerous trial registries and grey literature sources. In addition to this, we searched MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov, and the World Health Organization's trials portal, ICTRP, to ensure that searches were comprehensive and up-to-date. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that described interventions for people with mild to moderate dementia and compared CT versus a control or alternative intervention. DATA COLLECTION AND ANALYSIS: We extracted relevant data from published manuscripts and through contact with trial authors if required. We assessed risk of bias using the Cochrane 'Risk of bias' tool. We divided comparison conditions into active or passive control conditions and alternative treatments. We used a large number of measures and data to evaluate 19 outcomes at end of treatment, as well as 16 outcomes at follow-up in the medium term; we pooled this information in meta-analyses. We calculated pooled estimates of treatment effect using a random-effects model, and we estimated statistical heterogeneity using a standard Chi² statistic. We graded the evidence using GradePro. MAIN RESULTS: The 33 included trials were published between 1988 and 2018 and were conducted in 12 countries; most were unregistered, parallel-group, single-site RCTs, with samples ranging from 12 to 653 participants. Interventions were between two and 104 weeks long. We classified most experimental interventions as 'straight CT', but we classified some as 'augmented CT', and about two-thirds as multi-domain interventions. Researchers investigated 18 passive and 13 active control conditions, along with 15 alternative treatment conditions, including occupational therapy, mindfulness, reminiscence therapy, and others.The methodological quality of studies varied, but we rated nearly all studies as having high or unclear risk of selection bias due to lack of allocation concealment, and high or unclear risk of performance bias due to lack of blinding of participants and personnel.We used data from 32 studies in the meta-analysis of at least one outcome. Relative to a control condition, we found moderate-quality evidence showing a small to moderate effect of CT on our first primary outcome, composite measure of global cognition at end of treatment (standardised mean difference (SMD) 0.42, 95% confidence interval (CI) 0.23 to 0.62), and high-quality evidence showing a moderate effect on the secondary outcome of verbal semantic fluency (SMD 0.52, 95% CI 0.23 to 0.81) at end of treatment, with these gains retained in the medium term (3 to 12 months post treatment). In relation to many other outcomes, including our second primary outcome of clinical disease severity in the medium term, the quality of evidence was very low, so we were unable to determine whether CT was associated with any meaningful gains.When compared with an alternative treatment, we found that CT may have little to no effect on our first primary outcome of global cognition at end of treatment (SMD 0.21, 95% CI -0.23 to 0.64), but the quality of evidence was low. No evidence was available to assess our second primary outcome of clinical disease severity in the medium term. We found moderate-quality evidence showing that CT was associated with improved mood of the caregiver at end of treatment, but this was based on a single trial. The quality of evidence in relation to many other outcomes at end of treatment and in the medium term was too low for us to determine whether CT was associated with any gains, but we are moderately confident that CT did not lead to any gains in mood, behavioural and psychological symptoms, or capacity to perform activities of daily living. AUTHORS' CONCLUSIONS: Relative to a control intervention, but not to a variety of alternative treatments, CT is probably associated with small to moderate positive effects on global cognition and verbal semantic fluency at end of treatment, and these benefits appear to be maintained in the medium term. Our certainty in relation to many of these findings is low or very low. Future studies should take stronger measures to mitigate well-established risks of bias, and should provide long-term follow-up to improve our understanding of the extent to which observed gains are retained. Future trials should also focus on direct comparison of CT versus alternative treatments rather than passive or active control conditions.