Risk factors for apathy in Alzheimer’s disease: A systematic review of longitudinal evidence

BACKGROUND: Apathy is frequent and persistent in Alzheimer’s disease (AD), associated with poor prognosis and carer distress; yet our knowledge of risk factors remains limited. AIMS: To identify risk factors associated with apathy incidence and progression in AD over time. METHODS: We systematically reviewed evidence based on longitudinal studies assessing risk factors for apathy in AD up to June 2021. Two authors independently assessed article eligibility and rated quality. RESULTS: 13,280 articles were screened, of which 13 met inclusion criteria. Studies had a mean follow-up of 2.7 years reporting on a total of 2012 participants. Most findings were based on single studies of moderate quality evidence. Risk factors increasing apathy onset were: being a carrier of the T allele of the PRND gene polymorphism, and having high levels of the IL-6 and TNFα cytokines at baseline. Risk factors for apathy worsening were: reduced inferior-temporal cortical thickness, taking antidepressants, being an ApoE ε4 carrier, living longer with AD, lower cognitive test scores, higher baseline apathy, premorbid personality traits (lower agreeableness, higher neuroticism), and higher midlife motivational abilities. CONCLUSIONS: Although results are limited by the small number of studies, this review identified specific genetic, neurobiological, AD specific, and dispositional factors that may increase risk of apathy onset and worsening in AD

Association between Social Support and Depressive Symptoms in Informal Caregivers of Adult and Older Dependents: A Systematic Review and Meta-Analysis

Social support is an important determinant of a carer’s mental health. In recent decades, despite many studies reporting on the relationship between social support and depressive symptoms in informal caregivers of adult and older dependents, there are no systematic reviews synthesizing the available evidence. The purpose of the present study was to perform a systematic review and meta-analysis on the relationship between social support and depressive symptoms in informal caregivers of adults and older dependent people. We searched PubMed, CINAHL (EBSCO), PsycINFO (ProQuest), and Scopus, up to 15 January 2023 for studies. We applied no date or language limits to our search. A random-effects model was used to pool effect estimates. The included studies were also independently assessed for quality. Publication bias was evaluated by funnel plots, Egger’s regression test, and the Trim and Fill method. Ninety-three studies were included in the review, reporting on a total of 15,431 informal caregivers. We found a moderate negative association between perceived social support and caregiver depressive symptoms (78 studies; r = −0.35, 95% CI = −0.39, −0.31; low heterogeneity and low risk of publications bias) and a small negative association between received social support and caregiver self-reported depressive symptoms (12 studies; r = −0.14, 95% CI = −0.20, −0.07; low heterogeneity and low risk of publications bias). Our results indicate that social support is a clinically relevant construct for carer well-being and an important protective factor for depressive symptoms in informal caregivers of adult and older dependents

The Relationship between Social Support and Anxiety Symptoms in Informal Carers: A Systematic Review and Meta-Analysis

Background: Providing care can be challenging for informal carers and increases the risk of mental health problems, such as experiencing clinical symptoms of anxiety. While strengthening social support for informal carers is a common recommendation to reduce this risk, no systematic review or meta-analysis to date has examined the relationship between social support and anxiety symptoms in informal carers. The aim of our study was to systematically review the current evidence on the association between perceived and received social support and anxiety symptoms in informal carers of dependent adults and older people, and to comment on the quality of the evidence. / Methods: We searched PubMed, CINAHL (EBSCO), PsycINFO (ProQuest), Scopus, and LILACS up to 31 March 2021 for articles reporting on the association between caregiver anxiety symptoms and social support. A random-effects model was used to pool estimates, and each study was rated for quality using pre-specified criteria. Publication bias was assessed using a funnel plot and Egger’s regression test, which was adjusted using trim and fill analysis. / Results: From the 2180 identified articles, 35 studies met our inclusion criteria, reporting on 5036 informal carers in total. We found a moderate negative association between perceived social support and caregiver anxiety symptoms (r = −0.31, 95% CI = −0.35, −0.27) and a small, negative association between received social support and caregiver anxiety (r = −0.15, 95% CI = −0.22, −0.08). / Conclusion: The levels of perceived social support showed a significant negative association with caregiver anxiety symptoms. Policymakers and those working directly with informal carers should consider the development of targeted social support interventions that specifically enhance the levels of perceived social support to reduce symptoms of anxiety in informal carers

A predictive model of carer resilience in dementia family caregiving: A structural equation modelling approach

Objectives: This study aimed to investigate the mediating effects of quality of the caregiving relationship and other carer and person with dementia variables in predicting carer resilience over time. Method: Carers of people with mild and moderate dementia in community settings completed baseline (n = 176 dyads) and six‐month follow‐up assessments (n = 139 dyads). Causal mediation analysis was conducted using Pearson Correlation and Structural Equation Modelling (SEM) to examine longitudinal predictors of carer resilience, and the effect of several mediating person with dementia, and carer factors on carer resilience over time. Results: At 6‐month follow‐up, higher levels of carer resilience were longitudinally correlated with higher ratings of perceived relationship quality by people with dementia (r = 0.53 p ≤ 0.01), and lower levels of emotional distress symptoms by carer's (r = −0.59 p ≤ 0.01). Mediation analyses showed that people with dementia perspectives of the quality of the caregiving relationship mediated the relationship between carer distress specific to neuropsychiatric symptoms (β = −0.32, p ≤ 0.001) and carer resilience (β = 0.53, p ≤ 0.001) over time. The final SEM provided a good fit for the data (X 2 = 0.12, p = 0.72, CFI = 1.00, NFI = 0.99, and Root Mean Square Error of Approximation = 0.001). Conclusion: Higher ratings of perceived relationship quality by people with dementia, and lower levels of carer emotional distress predicted higher carer resilience at follow‐up. People with dementia perspectives of the quality of the caregiving relationship mediated the relationship between carer distress specific to neuropsychiatric symptoms and carer resilience over time. Our findings indicate that interventions aimed at strengthening the caregiving relationship might have a protective long‐term effect for carer resilience in dementia caregiving

Coping and depressive symptoms in family carers of dependent adults aged 18 and over: A systematic review and meta-analysis

Being a family carer is associated with increased risk of experiencing depressive symptoms. Despite many decades of research investigating the association between coping strategies and depressive symptoms in carers results across studies remain contradictory. The objective of this study was to systematically review evidence on the association between depressive symptoms and coping strategies in carers of dependent people aged 18 and over and investigate potential sources of heterogeneity of findings. The study design was a systematic review and meta-analysis. We searched Pubmed, CINAHL, PsycINFO and LILACS up to April 2021. We performed meta-analyses following the PRISMA statement and several subgroup analyses to investigate whether cause of caring dependency, study design, and controlling for several biases influenced results. Fifty-nine studies met our inclusion criteria. We found a robust and statistically significant association between greater use of dysfunctional coping and higher depressive symptoms. Greater use of emotion-focused coping was associated with fewer depressive symptoms only in studies controlling for confounding bias. Use of problem-focused coping was related to fewer depressive symptoms in carers of frail older people. The combined use of both problem-focused and emotion-focused coping was associated with lower symptoms of depression. Our review concludes that the broad domain of dysfunctional coping is consistently associated with higher levels of depressive symptoms in carers. After controlling for confounders, emotion-focused coping and several of its individual strategies were consistently associated with fewer depressive symptoms. Whilst problem-focused coping and some of its individual strategies are also associated with lower depressive symptoms, these strategies may not be as helpful in all caregiving groups.Clinical Impact Statement: fcBoth broad dimensions of coping and individual coping strategies are important correlates of depressive symptoms in family carers, and should be utilized in informing and improving the effectiveness of future caregiving interventions

Cognitive training interventions for dementia and mild cognitive impairment in Parkinson's disease

Background Approximately 60% to 80% of people with Parkinson's disease (PD) experience cognitive impairment that impacts on their quality of life. Cognitive decline is a core feature of the disease and can often present before the onset of motor symptoms. Cognitive training may be a useful non‐pharmacological intervention that could help to maintain or improve cognition and quality of life for people with PD dementia (PDD) or PD‐related mild cognitive impairment (PD‐MCI). Objectives To determine whether cognitive training (targeting single or multiple domains) improves cognition in people with PDD and PD‐MCI or other clearly defined forms of cognitive impairment in people with PD. Search methods We searched the Cochrane Dementia and Cognitive Improvement Group Trials Register (8 August 2019), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and PsycINFO. We searched reference lists and trial registers, searched relevant reviews in the area and conference proceedings. We also contacted experts for clarifications on data and ongoing trials. Selection criteria We included randomised controlled trials where the participants had PDD or PD‐MCI, and where the intervention was intended to train general or specific areas of cognitive function, targeting either a single domain or multiple domains of cognition, and was compared to a control condition. Multicomponent interventions that also included motor or other elements were considered eligible. Data collection and analysis Two review authors independently screened titles, abstracts, and full‐text articles for inclusion in the review. Two review authors also independently undertook extraction of data and assessment of methodological quality. We used GRADE methods to assess the overall quality of the evidence. Main results Seven studies with a total of 225 participants met the inclusion criteria for this review. All seven studies compared the effects of a cognitive training intervention to a control intervention at the end of treatment periods lasting four to eight weeks. Six studies included people with PD living in the community. These six studies recruited people with single‐domain (executive) or multiple‐domain mild cognitive impairment in PD. Four of these studies identified participants with MCI using established diagnostic criteria, and two included both people with PD‐MCI and people with PD who were not cognitively impaired. One study recruited people with a diagnosis of PD dementia who were living in long‐term care settings. The cognitive training intervention in three studies targeted a single cognitive domain, whilst in four studies multiple domains of cognitive function were targeted. The comparison groups either received no intervention or took part in recreational activities (sports, music, arts), speech or language exercises, computerised motor therapy, or motor rehabilitation combined with recreational activity. We found no clear evidence that cognitive training improved global cognition. Although cognitive training was associated with higher scores on global cognition at the end of treatment, the result was imprecise and not statistically significant (6 trials, 178 participants, standardised mean difference (SMD) 0.28, 95% confidence interval (CI) −0.03 to 0.59; low‐certainty evidence). There was no evidence of a difference at the end of treatment between cognitive training and control interventions on executive function (5 trials, 112 participants; SMD 0.10, 95% CI −0.28 to 0.48; low‐certainty evidence) or visual processing (3 trials, 64 participants; SMD 0.30, 95% CI −0.21 to 0.81; low‐certainty evidence). The evidence favoured the cognitive training group on attention (5 trials, 160 participants; SMD 0.36, 95% CI 0.03 to 0.68; low‐certainty evidence) and verbal memory (5 trials, 160 participants; SMD 0.37, 95% CI 0.04 to 0.69; low‐certainty evidence), but these effects were less certain in sensitivity analyses that excluded a study in which only a minority of the sample were cognitively impaired. There was no evidence of differences between treatment and control groups in activities of daily living (3 trials, 67 participants; SMD 0.03, 95% CI −0.47 to 0.53; low‐certainty evidence) or quality of life (5 trials, 147 participants; SMD −0.01, 95% CI −0.35 to 0.33; low‐certainty evidence). There was very little information on adverse events. We considered the certainty of the evidence for all outcomes to be low due to risk of bias in the included studies and imprecision of the results. We identified six ongoing trials recruiting participants with PD‐MCI, but no ongoing trials of cognitive training for people with PDD. Authors' conclusions This review found no evidence that people with PD‐MCI or PDD who receive cognitive training for four to eight weeks experience any important cognitive improvements at the end of training. However, this conclusion was based on a small number of studies with few participants, limitations of study design and execution, and imprecise results. There is a need for more robust, adequately powered studies of cognitive training before conclusions can be drawn about the effectiveness of cognitive training for people with PDD and PD‐MCI. Studies should use formal criteria to diagnose cognitive impairments, and there is a particular need for more studies testing the efficacy of cognitive training in people with PDD

REMCARE : pragmatic multi-centre randomised trial of reminiscence groups for people with dementia and their family carers : effectiveness and economic analysis

Background Joint reminiscence groups, involving people with dementia and family carers together, are popular, but the evidence-base is limited. This study aimed to assess the effectiveness and cost-effectiveness of joint reminiscence groups as compared to usual care. Methods This multi-centre, pragmatic randomised controlled trial had two parallel arms: intervention group and usual-care control group. A restricted dynamic method of randomisation was used, with an overall allocation ratio of 1:1, restricted to ensure viable sized intervention groups. Assessments, blind to treatment allocation, were carried out at baseline, three months and ten months (primary end-point), usually in the person's home. Participants were recruited in eight centres, mainly through NHS Memory Clinics and NHS community mental health teams. Included participants were community resident people with mild to moderate dementia (DSM-IV), who had a relative or other care-giver in regular contact, to act as informant and willing and able to participate in intervention. 71% carers were spouses. 488 people with dementia (mean age 77.5) were randomised: 268 intervention, 220 control; 350 dyads completed the study (206 intervention, 144 control). The intervention evaluated was joint reminiscence groups (with up to 12 dyads) weekly for twelve weeks; monthly maintenance sessions for further seven months. Sessions followed a published treatment manual and were held in a variety of community settings. Two trained facilitators in each centre were supported by volunteers. Primary outcome measures were self-reported quality of life for the person with dementia (QoL-AD), psychological distress for the carer (General Health Questionnaire, GHQ-28). Secondary outcome measures included: autobiographical memory and activities of daily living for the person with dementia; carer stress for the carer; mood, relationship quality and service use and costs for both. Results The intention to treat analysis (ANCOVA) identified no differences in outcome between the intervention and control conditions on primary or secondary outcomes (self-reported QoL-AD mean difference 0.07 (-1.21 to 1.35), F = 0.48, p = 0.53). Carers of people with dementia allocated to the reminiscence intervention reported a significant increase in anxiety on a General Health Questionnaire-28 sub-scale at the ten month end-point (mean difference 1.25 (0.25 to 2.26), F = 8.28, p = 0.04). Compliance analyses suggested improved autobiographical memory, quality of life and relationship quality for people with dementia attending more reminiscence sessions, however carers attending more groups showed increased care-giving stress. Economic analyses from a public sector perspective indicated that joint reminiscence groups are unlikely to be cost-effective. There were no significant adverse effects attributed to the intervention. Potential limitations of the study include less than optimal attendance at the group sessions—only 57% of participants attended at least half of the intervention sessions over the 10 month period, and a higher rate of study withdrawal in the control group. Conclusions This trial does not support the clinical effectiveness or cost-effectiveness of joint reminiscence groups. Possible beneficial effects for people with dementia who attend sessions as planned are offset by raised anxiety and stress in their carers. The reasons for these discrepant outcomes need to be explored further, and may necessitate reappraisal of the movement towards joint interventions

The use of the EQ-5D as a measure of health-related quality of life in people with dementia and their carers

To assess the acceptability, validity and inter-rater agreement of self- and family carer proxy ratings of the EQ-5D as a generic health-related quality of life (HRQOL) measure, in people with mild to moderate dementia (PwD) living in the community. A secondary aim was to identify the most important factors influencing self- and family carer proxy ratings of HRQOL, distinguishing between spouse and adult child caregiver ratings

Association between anxiety symptoms and Alzheimer's disease biomarkers in cognitively healthy adults: A systematic review and meta-analysis

Objective: Anxiety has been identified as both a risk factor and prodromal symptom for Alzheimer's disease (AD) and related dementias, however, the underlying neurobiological correlates remain unknown. The aim of this systematic review and meta-analysis was to examine the association between anxiety symptoms and two defining markers of AD neuropathology: amyloid-beta (Aβ) and tau. Methods: Systematic literature searches were conducted across 5 databases. Studies investigating the relationship between anxiety and AD neuropathology (i.e., Aβ and/or tau) in cognitively healthy adults were eligible. Where possible, effect sizes were combined across studies, for Aβ and tau separately, using random-effects meta-analyses. Sensitivity analyses were performed to assess whether results differed according to anxiety type (i.e., state and trait) and biomarker assessment modality (i.e., positron emission tomography and cerebrospinal fluid). Results: Twenty-seven studies reporting data from 14 unique cohorts met eligibility criteria. Random-effects meta-analyses revealed no associations between self-reported anxiety symptoms and either Aβ (13 studies, Fisher's z = 0.02, 95% confidence interval [CI] -0.01–0.05, p = 0.194) or tau (4 studies, Fisher's z = 0.04, 95% CI -0.02–0.09, p = 0.235). Results remained unchanged across sensitivity analyses. Conclusions: In cognitively healthy adults, meta-analytic syntheses revealed no associations between anxiety symptoms and either Aβ or tau. There is a critical need, however, for larger studies with follow-up periods to examine the effect of anxiety symptom onset, severity, and chronicity on AD neuropathology. Additionally, further research investigating other potential neurobiological correlates is crucial to advance scientific understanding of the relationship between anxiety and dementia

Individual cognitive stimulation therapy for dementia : a clinical effectiveness and cost-effectiveness pragmatic, multicentre, randomised controlled trial

Background Group cognitive stimulation therapy programmes can benefit cognition and quality of life for people with dementia. Evidence for home-based, carer-led cognitive stimulation interventions is limited. Objectives To evaluate the clinical effectiveness and cost-effectiveness of carer-delivered individual cognitive stimulation therapy (iCST) for people with dementia and their family carers, compared with treatment as usual (TAU). Design A multicentre, single-blind, randomised controlled trial assessing clinical effectiveness and cost-effectiveness. Assessments were at baseline, 13 weeks and 26 weeks (primary end point). Setting Participants were recruited through Memory Clinics and Community Mental Health Teams for older people. Participants A total of 356 caregiving dyads were recruited and 273 completed the trial. Intervention iCST consisted of structured cognitive stimulation sessions for people with dementia, completed up to three times weekly over 25 weeks. Family carers were supported to deliver the sessions at home. Main outcome measures Primary outcomes for the person with dementia were cognition and quality of life. Secondary outcomes included behavioural and psychological symptoms, activities of daily living, depressive symptoms and relationship quality. The primary outcome for the family carers was mental/physical health (Short Form questionnaire-12 items). Health-related quality of life (European Quality of Life-5 Dimensions), mood symptoms, resilience and relationship quality comprised the secondary outcomes. Costs were estimated from health and social care and societal perspectives. Results There were no differences in any of the primary outcomes for people with dementia between intervention and TAU [cognition: mean difference –0.55, 95% confidence interval (CI) –2.00 to 0.90; p-value = 0.45; self-reported quality of life: mean difference –0.02, 95% CI –1.22 to 0.82; p-value = 0.97 at the 6-month follow-up]. iCST did not improve mental/physical health for carers. People with dementia in the iCST group experienced better relationship quality with their carer, but there was no evidence that iCST improved their activities of daily living, depression or behavioural and psychological symptoms. iCST seemed to improve health-related quality of life for carers but did not benefit carers’ resilience or their relationship quality with their relative. Carers conducting more sessions had fewer depressive symptoms. Qualitative data suggested that people with dementia and their carers experienced better communication owing to iCST. Adjusted mean costs were not significantly different between the groups. From the societal perspective, both health gains and cost savings were observed. Conclusions iCST did not improve cognition or quality of life for people with dementia, or carers’ physical and mental health. Costs of the intervention were offset by some reductions in social care and other services. Although there was some evidence of improvement in terms of the caregiving relationship and carers’ health-related quality of life, iCST does not appear to deliver clinical benefits for cognition and quality of life for people with dementia. Most people received fewer than the recommended number of iCST sessions. Further research is needed to ascertain the clinical effectiveness of carer-led cognitive stimulation interventions for people with dementia