OBJECTIVE: We conducted this systematic review to support the U.S. Preventive Services Task Force in updating its 2014 recommendation on screening for cognitive impairment in older adults. Our review addressed the direct evidence on the benefits and harms of screening for cognitive impairment versus no screening, the test accuracy of screening instruments to detect mild cognitive impairment (MCI) and dementia, and the benefits and harms of treatment for MCI and mild to moderate dementia among community-dwelling older adults age 65 years and older.
DATA SOURCES: We performed an updated search of MEDLINE, PubMed Publisher-Supplied, PsycINFO, and the Cochrane Central Register of Controlled Trials for studies published through January 2019. We supplemented searches by examining reference lists from related articles and expert recommendations and searched federal and international trial registries for ongoing trials.
STUDY SELECTION: Two researchers reviewed 11,644 titles and abstracts and 966 full-text articles against prespecified inclusion criteria. We included test accuracy studies that included screening instruments that could be delivered in primary care in 10 minutes or less by a clinician or self-administered in 20 minutes or less compared with a reference standard. We included trials of major pharmacologic and nonpharmacologic interventions in persons with MCI or mild to moderate dementia and large, observational studies examining adverse effects of these interventions. We conducted dual, independent critical appraisal of all provisionally included studies and abstracted all important study details and results from all studies rated fair or good quality. Data were abstracted by one reviewer and confirmed by another.
DATA ANALYSIS: We synthesized data separately for each key question and within subcategories of screening instruments and treatments. For diagnostic accuracy studies, we focused on sensitivity and specificity of instruments that were evaluated in more than one study. We conducted a qualitative synthesis of results using summary tables and figures to capture key study characteristics, sources of clinical heterogeneity, and overall results of each study. Quantitative synthesis was limited to test performance of the Mini Mental State Examination (MMSE) (due to insufficient number of homogeneous studies for other instruments) and U.S. Food and Drug Administration (FDA)–approved medications to treat Alzheimer’s Disease on global cognitive outcomes, global function, and harms; nonpharmacologic interventions aimed at the patient on global cognitive outcomes; and caregiver and caregiver-patient dyad interventions on caregiver burden and depression outcomes. We ran random-effects meta-analyses using the DerSimonian and Laird method and sensitivity analyses using a Restricted Likelihood Estimation Model with the Knapp-Hartung correction to calculate the pooled differences in mean changes (for continuous data) and pooled risk ratio (for binary data). We used meta-regression to explore potential effect modification by various study, population, and intervention characteristics in cases where 10 or more studies were pooled. We generated funnel plots and conducted tests for small-study effects for all pooled analyses. Using established methods, we assessed the strength of evidence for each question.
RESULTS: Screening (Key Questions 1–3): Only one trial was identified that examined the direct effect of screening for cognitive impairment on important patient outcomes, including potential harms. In that trial, at 12 months, there was no difference in health-related quality of life between those who were screened vs. not screened. Symptoms of depression and anxiety were also similar between groups at 1, 6, and 12 months as was health care utilization and advance care planning. We identified 59 studies that addressed the diagnostic accuracy of 49 screening instruments to detect cognitive impairment. Most instruments were only studied in a handful of well-designed diagnostic accuracy studies in primary care–relevant populations. The MMSE, a brief test taking 7 to 10 minutes to complete, remains the most thoroughly studied instrument. The pooled estimate across 15 studies (n=12,796) resulted in 89 percent sensitivity (95% CI, 0.85 to 0.92) and 89 percent specificity (95% CI, 0.85 to 0.93) to detect dementia at a cutoff of 23 or less or 24 or less. Other screening instruments evaluated in more than one study included the very brief instruments (≤5 minutes) of the CDT, MIS, MSQ, Mini-Cog, Lawton IADL, VF, AD8, and FAQ and the brief instruments (6 to 10 minutes) of the 7MS, AMT, MoCA, SLUMS, and TICS with sensitivity to detect dementia usually at 0.75 or higher and specificity at 0.80 or higher for all instruments. For self-administered, longer tests (>10 minutes), only the IQCODE was assessed in more than one study, with sensitivity to detect dementia ranging from 0.80 to 0.88 and specificity ranging from 0.51 to 0.91. Across all instruments, test performance was generally higher in the detection of dementia vs. mild cognitive impairment, although confidence intervals overlapped. No studies directly addressed the adverse psychological effects of screening or adverse effects from false-positive or false-negative testing. Treatment (Key Questions 4 and 5): We identified 224 trials and 3 observational studies representing more than 240,000 patients and/or caregivers that addressed the treatment or management of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, trial participants were persons with known MCI or dementia. Pharmacologic Interventions: Based on 45 trials (n=22,431) and three observational studies (n=190,076) that evaluated acetylcholinesterase inhibitors (AChEIs) (i.e., donepezil, galantamine, rivastigmine) and memantine, these medications may improve measures of global cognitive function in the short term, but the magnitude of change is small. In meta-analyses, the differences in changes between those on AChEIs or memantine compared with those on placebo ranged from approximately 1 to 2.5 points on the ADAS-Cog-11 and 0.5 to 1 point on the MMSE over 3 months to 3 years of followup. AChEIs and memantine appeared to increase the likelihood of improving or maintaining patients’ global function by 15 percent (for memantine) to 50 percent (for rivastigmine) in the short term (pooled 95% confidence interval range, 0.49 to 2.69). Other outcome measures were inconsistently reported. Total adverse events and discontinuation due to adverse events were more common with AChEIs, but not memantine, compared with placebo. Rates of serious adverse events overall were not higher among those taking medications vs. placebo, but individual studies noted increased rates of serious adverse events. Trials evaluating other medications or dietary supplements (k=29; n=6,489), including discontinuing antihypertensives, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (atorvastatin and simvastatin), nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen, indomethacin, and celecoxib), gonadal steroids (estrogen [plus or minus progesterone] and testosterone), and dietary supplements and vitamins (multivitamins, B vitamins, vitamin E, and omega-3 fatty acids) showed no benefit on global cognitive or physical function in persons with mild to moderate dementia or MCI. Nonpharmacologic Interventions: We identified 61 trials (n=7,847) that evaluated nonpharmacologic patient-level interventions, including cognitive-focused, exercise, and multicomponent and other interventions. Among all interventions, there was no clear benefit on global or domain-specific measures of cognitive function compared with control conditions at 3 months to 2 years followup. Effect estimates generally favored the intervention groups over control groups, but the magnitude of effect was inconsistent across trials and represented very wide confidence intervals (ranging from no effect to a large effect). Physical function outcomes, including change in activities of daily living and independent activities of daily living, as well as quality of life and mental and neuropsychiatric symptoms, were inconsistently reported. There was, however, a pattern of effect for exercise interventions, with small improvements seen in measures of physical function and symptoms for intervention groups, whereas control groups reported worsening function. Caregiver and caregiver-patient dyad interventions including psychoeducation for the caregiver and care and case management interventions, reported in 88 trials (n=14,880), resulted in a consistent benefit on caregiver burden and depression outcomes. Effect sizes were mostly small, however, and were of unclear clinical significance. Little harm was evident in the few nonpharmacologic intervention trials that reported harms.
LIMITATIONS: There is a lack of evidence around how screening for and treating MCI and early-stage dementia affects decision making outcomes. Furthermore, there has been little reproducibility in testing specific screening instruments in primary care populations. The treatment literature is limited by a lack of consistency in the specific outcomes reported and short followup duration. It is difficult to interpret the clinical importance of the small average effects seen among treatment trials, and many measures likely have limited responsiveness for patients with less pronounced cognitive impairment. Consistent and standardized reporting of results according to meaningful thresholds of clinical significance would be helpful in interpreting the small average effects on continuous outcome measures. Other important measures such as quality of life, physical function, and institutionalization, were inconsistently reported.
CONCLUSIONS: Several brief screening instruments can adequately detect cognitive impairment, especially in populations with a higher prevalence of underlying dementia. There is no empiric evidence, however, that screening for cognitive impairment or early diagnosis of cognitive impairment improves patient, caregiver, family, or clinician decision making or other important outcomes nor causes harm. In general, there is support that AChEIs and memantine and interventions that support caregivers, including those that help coordinate care for patients and caregivers, can result in small improvements in the short term. Unfortunately, the average effects of these benefits are quite small and likely not of clinical significance. Any benefits are further limited by the commonly experienced side effects of medications and the limited availability of complex caregiver interventions. Cognitive stimulation and training, exercise interventions, and other medications and supplements showed some favorable effects on patients’ cognitive and physical function, but trial evidence lacked consistency and the estimates of benefit were imprecise. There is less evidence related to screening for and treating MCI. The test performance of the few instruments evaluated to detect MCI was lower than the sensitivity and specificity to detect dementia and there is little evidence for any pharmacologic or nonpharmacologic interventions to preserve or improve patient functioning in persons with MCI.
AIMS: (1) To evaluate the effectiveness of different types of psychosocial interventions on the health-related quality of life among caregivers of individuals with dementia; and (2) To present an overview and assessment of the quality of the most recent intervention studies.
DESIGN: A systematic review and meta-analysis.
DATA SOURCES: MEDLINE, CINAHL, PsycINFO and Cochrane Library electronic databases were searched to find randomized controlled trials (RCTs) published from 2005 to 2017. Using a Boolean search, the key words "caregivers," "dementia," and "quality of life" were combined. The search was completed in January 2018.
REVIEW METHODS: A total of 26 RCTs were included. Intervention details such as content, mode of delivery and duration were reviewed, and each study's risk of bias was assessed. The effectiveness of each type of intervention was calculated using the Hedges G and a random-effects model.
RESULTS: Multicomponent interventions, cognitive-behavioral therapy and complementary alternative medicine therapy showed significant effects on improving caregiver's health-related quality of life. Psychoeducation, social support, case management and cognitive rehabilitation therapy failed to produce significant effects.
CONCLUSION: Via this evidence-based systematic review, multicomponent interventions addressing a variety of caregiver needs can be an effective method for enhancing caregiver health-related quality of life. Further large number of studies are needed to verify this study results.
IMPACT: The findings of this study inform clinicians which interventions are effective in improving caregivers' health-related quality of life. Defining a standardized protocol for multicomponent interventions will be helpful for clinicians to apply the intervention.
IMPORTANCE: Early identification of cognitive impairment may improve patient and caregiver health outcomes.
OBJECTIVE: To systematically review the test accuracy of cognitive screening instruments and benefits and harms of interventions to treat cognitive impairment in older adults (≥65 years) to inform the US Preventive Services Task Force.
DATA SOURCES: MEDLINE, PubMed, PsycINFO, and Cochrane Central Register of Controlled Trials through January 2019, with literature surveillance through November 22, 2019.
STUDY SELECTION: Fair- to good-quality English-language studies of cognitive impairment screening instruments, and pharmacologic and nonpharmacologic treatments aimed at persons with mild cognitive impairment (MCI), mild to moderate dementia, or their caregivers.
DATA EXTRACTION AND SYNTHESIS: Independent critical appraisal and data abstraction; random-effects meta-analyses and qualitative synthesis.
MAIN OUTCOMES AND MEASURES: Sensitivity, specificity; patient, caregiver, and clinician decision-making; patient function, quality of life, and neuropsychiatric symptoms; caregiver burden and well-being.
RESULTS: The review included 287 studies with more than 280 000 older adults. One randomized clinical trial (RCT) (n = 4005) examined the direct effect of screening for cognitive impairment on patient outcomes, including potential harms, finding no significant differences in health-related quality of life at 12 months (effect size, 0.009 [95% CI, -0.063 to 0.080]). Fifty-nine studies (n = 38 531) addressed the accuracy of 49 screening instruments to detect cognitive impairment. The Mini-Mental State Examination was the most-studied instrument, with a pooled sensitivity of 0.89 (95% CI, 0.85 to 0.92) and specificity of 0.89 (95% CI, 0.85 to 0.93) to detect dementia using a cutoff of 23 or less or 24 or less (15 studies, n = 12 796). Two hundred twenty-four RCTs and 3 observational studies including more than 240 000 patients or caregivers addressed the treatment of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, participants were persons with known cognitive impairment. Medications approved to treat Alzheimer disease (donepezil, galantamine, rivastigmine, and memantine) improved scores on the ADAS-Cog 11 by 1 to 2.5 points over 3 months to 3 years. Psychoeducation interventions for caregivers resulted in a small benefit for caregiver burden (standardized mean difference, -0.24 [95% CI, -0.36 to -0.13) over 3 to 12 months. Intervention benefits were small and of uncertain clinical importance.
CONCLUSIONS AND RELEVANCE: Screening instruments can adequately detect cognitive impairment. There is no empirical evidence, however, that screening for cognitive impairment improves patient or caregiver outcomes or causes harm. It remains unclear whether interventions for patients or caregivers provide clinically important benefits for older adults with earlier detected cognitive impairment or their caregivers.
BACKGROUND: Persons with dementia have twice the acute hospital use as older persons without dementia. In addition to straining overburdened healthcare systems, acute hospital use impacts patient and caregiver quality of life and is associated with increased risk of adverse outcomes including death. Reducing avoidable acute hospital use in persons with dementia is thus a global healthcare priority. However, evidence regarding the impact of health service interventions as defined by the Effective Practice and Organization of Care Cochrane Group on acute hospital use is scant and inconclusive. The aim of this systematic review and meta-analysis was to synthesize available evidence on the impact of health service interventions on acute hospital use in community-dwelling persons with dementia compared to usual care.
METHODS: Data Sources: MEDLINE, EMBASE, CINAHL and Cochrane CENTRAL (from 01/1995 to 08/2017). Study eligibility criteria: Randomised controlled trials measuring the impact of health service interventions on acute hospital use (proportion and mean number of emergency department visits and hospitalisations, mean number of hospital days, measured at 12 months, and at longest follow-up) in community-dwelling persons with dementia, compared to usual care. Study selection, appraisal and synthesis methods: Reviewers independently identified studies, extracted data, and assessed the risk of bias, with the Cochrane risk of bias tool. Authors of relevant trials were queried about unpublished data. Random effects model was used for meta-analyses. Effect heterogeneity was assessed through prediction intervals, and explored using sub-group analyses.
FINDINGS: Seventeen trials provided data on 4,549 persons. Unpublished data were obtained for 13 trials, representing 65% of synthesized data. Most interventions included a case management or a self-management component. None of the outcome comparisons provided conclusive evidence supporting the hypothesis that these interventions would lead to a decrease in acute hospital use. Furthermore, prediction intervals indicated possible and important increased service use associated with these interventions, such as emergency department visits, hospital admissions, and hospital days. Subgroup analyses did not favour any type of intervention. A limitation of this study is the inclusion of any type of health service intervention, which may have increased the observed heterogeneity.
CONCLUSION: Despite a comprehensive systematic review and meta-analysis, including predominantly unpublished data, no health service intervention beyond usual care was found to reduce acute hospital use in community-dwelling persons with dementia. An important increase in service use may be associated with these interventions. Further research is urgently needed to identify effective interventions for this vulnerable population to limit rising acute hospital use, associated costs and adverse outcomes. Systematic review registration PROSPERO CRD42016046444.
ABSTRACTObjective:The aim of this study was to update the literature on interventions for carers of people with dementia published between 2006 and 2016 and evaluate the efficacy of psychoeducational programs and psychotherapeutic interventions on key mental health outcomes (depression, anxiety, burden, and quality of life).
METHODS: A meta-analysis was carried out of randomized controlled trials of carer interventions using MEDLINE, PsycINFO, Scopus, and Cochrane Central Register of Controlled Trials.
RESULTS: The majority of studies were conducted in Western and Southern Europe or the United States and recruited carers of people with Alzheimer's disease or dementia grouped as a whole. The most commonly used outcome measures were depression and burden across studies. The updated evidence suggested that psychoeducation-skill building interventions delivered face-to-face can better impact on burden. Psychotherapeutic interventions underpinned by Cognitive Behavior Therapy (CBT) models demonstrated strong empirical support for treating anxiety and depression and these effects were not affected by the mode of delivery (i.e. face-to-face vs. technology). A modern CBT approach, Acceptance and Commitment Therapy (ACT), seemed to be particularly beneficial for carers experiencing high levels of anxiety.
CONCLUSIONS: Future research needs to explore the efficacy of interventions on multiple clinical outcomes and which combination of interventions (components) would have the most significant effects when using CBT. The generalization of treatment effects in different countries and carers of different types of dementia also need to be addressed. More research is needed to test the efficacy of modern forms of CBT, such as ACT.
OBJECTIVE: The aim of this study was to compare the efficacy of two approaches: multicomponent interventions that focus on working with the carer and dyadic interventions that work with both the carer and the person with dementia.
METHOD: A systematic review involving a search of Medline, EMBASE, and PsycINFO in October 2015 was performed. Randomized controlled trials involving carers of people with dementia and comparing multicomponent interventions with usual care were included.
RESULTS: Pooling of all studies demonstrated that multicomponent interventions can reduce depressive symptoms, improve quality of life, reduce carer impact, and reduce behavioral and psychological symptoms of dementia as well as caregiver upset with these symptoms. We were unable to find a significant difference in the effects of dyadic interventions in comparison with carer focused interventions for these outcomes.
DISCUSSION: Although effect sizes associated with intervention are small, multicomponent interventions are relatively inexpensive to deliver, acceptable, and widely applicable.
BACKGROUND: Over 35 million people are estimated to be living with dementia in the world and the societal costs are very high. Case management is a widely used and strongly promoted complex intervention for organising and co-ordinating care at the level of the individual, with the aim of providing long-term care for people with dementia in the community as an alternative to early admission to a care home or hospital.
OBJECTIVES: To evaluate the effectiveness of case management approaches to home support for people with dementia, from the perspective of the different people involved (patients, carers, and staff) compared with other forms of treatment, including ‘treatment as usual’, standard community treatment and other non-case management interventions.
SEARCH METHODS: We searched the following databases up to 31 December 2013: ALOIS, the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group,The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, Web of Science (including Science Citation Index Expanded (SCI-EXPANDED) and Social Science Citation Index), Campbell Collaboration/SORO database and the Specialised Register of the Cochrane Effective Practice and Organisation of Care Group. We updated this search in March 2014 but results have not yet been incorporated.
SELECTION CRITERIA: We include randomised controlled trials (RCTs) of case management interventions for people with dementia living in the community and their carers. We screened interventions to ensure that they focused on planning and co-ordination of care.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as required by The Cochrane Collaboration. Two review authors independently extracted data and made 'Risk of bias' assessments using Cochrane criteria. For continuous outcomes, we used the mean difference (MD) or standardised mean difference (SMD) between groups along with its confidence interval (95% CI). We applied a fixed- or random-effects model as appropriate. For binary or dichotomous data, we generated the corresponding odds ratio (OR) with 95% CI. We assessed heterogeneity by the I² statistic.
MAIN RESULTS: We include 13 RCTs involving 9615 participants with dementia in the review. Case management interventions in studies varied. We found low to moderate overall risk of bias; 69% of studies were at high risk for performance bias.
The case management group were significantly less likely to be institutionalised (admissions to residential or nursing homes) at six months (OR 0.82, 95% CI 0.69 to 0.98, n = 5741, 6 RCTs, I² = 0%, P = 0.02) and at 18 months (OR 0.25, 95% CI 0.10 to 0.61, n = 363, 4 RCTs, I² = 0%, P = 0.003). However, the effects at 10 - 12 months (OR 0.95, 95% CI 0.83 to 1.08, n = 5990, 9 RCTs, I² = 48%, P = 0.39) and 24 months (OR 1.03, 95% CI 0.52 to 2.03, n = 201, 2 RCTs, I² = 0%, P = 0.94) were uncertain. There was evidence from one trial of a reduction in the number of days per month in a residential home or hospital unit in the case management group at six months (MD -5.80, 95% CI -7.93 to -3.67, n = 88, 1 RCT, P < 0.0001) and at 12 months (MD -7.70, 95% CI -9.38 to -6.02, n = 88, 1 RCT, P < 0.0001). One trial reported the length of time until participants were institutionalised at 12 months and the effects were uncertain (hazard ratio (HR): 0.66, 95% CI 0.38 to 1.14, P = 0.14). There was no difference in the number of people admitted to hospital at six (4 RCTs, 439 participants), 12 (5 RCTs, 585 participants) and 18 months (5 RCTs, 613 participants). For mortality at 4 - 6, 12, 18 - 24 and 36 months, and for participants' or carers' quality of life at 4, 6, 12 and 18 months, there were no significant effects. There was some evidence of benefits in carer burden at six months (SMD -0.07, 95% CI -0.12 to -0.01, n = 4601, 4 RCTs, I² = 26%, P = 0.03) but the effects at 12 or 18 months were uncertain. Additionally, some evidence indicated case management was more effective at reducing behaviour disturbance at 18 months (SMD -0.35, 95% CI -0.63 to -0.07, n = 206, 2 RCTs I² = 0%, P = 0.01) but effects were uncertain at four (2 RCTs), six (4 RCTs) or 12 months (5 RCTs).
The case management group showed a small significant improvement in carer depression at 18 months (SMD -0.08, 95% CI -0.16 to -0.01, n = 2888, 3 RCTs, I² = 0%, P = 0.03). Conversely, the case management group showed greater improvement in carer well-being in a single study at six months (MD -2.20 CI CI -4.14 to -0.26, n = 65, 1 RCT, P = 0.03) but the effects were uncertain at 12 or 18 months. There was some evidence that case management reduced the total cost of services at 12 months (SMD -0.07, 95% CI -0.12 to -0.02, n = 5276, 2 RCTs, P = 0.01) and incurred lower dollar expenditure for the total three years (MD= -705.00, 95% CI -1170.31 to -239.69, n = 5170, 1 RCT, P = 0.003). Data on a number of outcomes consistently indicated that the intervention group received significantly more community services.
AUTHORS' CONCLUSIONS: There is some evidence that case management is beneficial at improving some outcomes at certain time points, both in the person with dementia and in their carer. However, there was considerable heterogeneity between the interventions, outcomes measured and time points across the 13 included RCTs. There was some evidence from good-quality studies to suggest that admissions to care homes and overall healthcare costs are reduced in the medium term; however, the results at longer points of follow-up were uncertain. There was not enough evidence to clearly assess whether case management could delay institutionalisation in care homes. There were uncertain results in patient depression, functional abilities and cognition. Further work should be undertaken to investigate what components of case management are associated with improvement in outcomes. Increased consistency in measures of outcome would support future meta-analysis.
PURPOSE: Results of case management designed for patients with dementia and their caregivers in community-based primary health care (CBPHC) were inconsistent. Our objective was to identify the relationships between key outcomes of case management and barriers to implementation. METHODS: We conducted a systematic mixed studies review (including quantitative and qualitative studies). Literature search was performed in MEDLINE, PsycINFO, Embase, and Cochrane Library (1995 up to August 2012). Case management intervention studies were used to assess clinical outcomes for patients, service use, caregiver outcomes, satisfaction, and cost-effectiveness. Qualitative studies were used to examine barriers to case management implementation. Patterns in the relationships between barriers to implementation and outcomes were identified using the configurational comparative method. The quality of studies was assessed using the Mixed Methods Appraisal Tool. RESULTS: Forty-three studies were selected (31 quantitative and 12 qualitative). Case management had a limited positive effect on behavioral symptoms of dementia and length of hospital stay for patients and on burden and depression for informal caregivers. Interventions that addressed a greater number of barriers to implementation resulted in increased number of positive outcomes. Results suggested that high-intensity case management was necessary and sufficient to produce positive clinical outcomes for patients and to optimize service use. Effective communication within the CBPHC team was necessary and sufficient for positive outcomes for caregivers. CONCLUSIONS: Clinicians and managers who implement case management in CBPHC should take into account high-intensity case management (small caseload, regular proactive patient follow-up, regular contact between case managers and family physicians) and effective communication between case managers and other CBPHC professionals and services.
We conducted this systematic review to support the U.S. Preventive Services Task Force in updating its 2014 recommendation on screening for cognitive impairment in older adults. Our review addressed the direct evidence on the benefits and harms of screening for cognitive impairment versus no screening, the test accuracy of screening instruments to detect mild cognitive impairment (MCI) and dementia, and the benefits and harms of treatment for MCI and mild to moderate dementia among community-dwelling older adults age 65 years and older.
DATA SOURCES:
We performed an updated search of MEDLINE, PubMed Publisher-Supplied, PsycINFO, and the Cochrane Central Register of Controlled Trials for studies published through January 2019. We supplemented searches by examining reference lists from related articles and expert recommendations and searched federal and international trial registries for ongoing trials.
STUDY SELECTION:
Two researchers reviewed 11,644 titles and abstracts and 966 full-text articles against prespecified inclusion criteria. We included test accuracy studies that included screening instruments that could be delivered in primary care in 10 minutes or less by a clinician or self-administered in 20 minutes or less compared with a reference standard. We included trials of major pharmacologic and nonpharmacologic interventions in persons with MCI or mild to moderate dementia and large, observational studies examining adverse effects of these interventions. We conducted dual, independent critical appraisal of all provisionally included studies and abstracted all important study details and results from all studies rated fair or good quality. Data were abstracted by one reviewer and confirmed by another.
DATA ANALYSIS:
We synthesized data separately for each key question and within subcategories of screening instruments and treatments. For diagnostic accuracy studies, we focused on sensitivity and specificity of instruments that were evaluated in more than one study. We conducted a qualitative synthesis of results using summary tables and figures to capture key study characteristics, sources of clinical heterogeneity, and overall results of each study. Quantitative synthesis was limited to test performance of the Mini Mental State Examination (MMSE) (due to insufficient number of homogeneous studies for other instruments) and U.S. Food and Drug Administration (FDA)–approved medications to treat Alzheimer’s Disease on global cognitive outcomes, global function, and harms; nonpharmacologic interventions aimed at the patient on global cognitive outcomes; and caregiver and caregiver-patient dyad interventions on caregiver burden and depression outcomes. We ran random-effects meta-analyses using the DerSimonian and Laird method and sensitivity analyses using a Restricted Likelihood Estimation Model with the Knapp-Hartung correction to calculate the pooled differences in mean changes (for continuous data) and pooled risk ratio (for binary data). We used meta-regression to explore potential effect modification by various study, population, and intervention characteristics in cases where 10 or more studies were pooled. We generated funnel plots and conducted tests for small-study effects for all pooled analyses. Using established methods, we assessed the strength of evidence for each question.
RESULTS:
Screening (Key Questions 1–3): Only one trial was identified that examined the direct effect of screening for cognitive impairment on important patient outcomes, including potential harms. In that trial, at 12 months, there was no difference in health-related quality of life between those who were screened vs. not screened. Symptoms of depression and anxiety were also similar between groups at 1, 6, and 12 months as was health care utilization and advance care planning. We identified 59 studies that addressed the diagnostic accuracy of 49 screening instruments to detect cognitive impairment. Most instruments were only studied in a handful of well-designed diagnostic accuracy studies in primary care–relevant populations. The MMSE, a brief test taking 7 to 10 minutes to complete, remains the most thoroughly studied instrument. The pooled estimate across 15 studies (n=12,796) resulted in 89 percent sensitivity (95% CI, 0.85 to 0.92) and 89 percent specificity (95% CI, 0.85 to 0.93) to detect dementia at a cutoff of 23 or less or 24 or less. Other screening instruments evaluated in more than one study included the very brief instruments (≤5 minutes) of the CDT, MIS, MSQ, Mini-Cog, Lawton IADL, VF, AD8, and FAQ and the brief instruments (6 to 10 minutes) of the 7MS, AMT, MoCA, SLUMS, and TICS with sensitivity to detect dementia usually at 0.75 or higher and specificity at 0.80 or higher for all instruments. For self-administered, longer tests (>10 minutes), only the IQCODE was assessed in more than one study, with sensitivity to detect dementia ranging from 0.80 to 0.88 and specificity ranging from 0.51 to 0.91. Across all instruments, test performance was generally higher in the detection of dementia vs. mild cognitive impairment, although confidence intervals overlapped. No studies directly addressed the adverse psychological effects of screening or adverse effects from false-positive or false-negative testing. Treatment (Key Questions 4 and 5): We identified 224 trials and 3 observational studies representing more than 240,000 patients and/or caregivers that addressed the treatment or management of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, trial participants were persons with known MCI or dementia. Pharmacologic Interventions: Based on 45 trials (n=22,431) and three observational studies (n=190,076) that evaluated acetylcholinesterase inhibitors (AChEIs) (i.e., donepezil, galantamine, rivastigmine) and memantine, these medications may improve measures of global cognitive function in the short term, but the magnitude of change is small. In meta-analyses, the differences in changes between those on AChEIs or memantine compared with those on placebo ranged from approximately 1 to 2.5 points on the ADAS-Cog-11 and 0.5 to 1 point on the MMSE over 3 months to 3 years of followup. AChEIs and memantine appeared to increase the likelihood of improving or maintaining patients’ global function by 15 percent (for memantine) to 50 percent (for rivastigmine) in the short term (pooled 95% confidence interval range, 0.49 to 2.69). Other outcome measures were inconsistently reported. Total adverse events and discontinuation due to adverse events were more common with AChEIs, but not memantine, compared with placebo. Rates of serious adverse events overall were not higher among those taking medications vs. placebo, but individual studies noted increased rates of serious adverse events. Trials evaluating other medications or dietary supplements (k=29; n=6,489), including discontinuing antihypertensives, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (atorvastatin and simvastatin), nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen, indomethacin, and celecoxib), gonadal steroids (estrogen [plus or minus progesterone] and testosterone), and dietary supplements and vitamins (multivitamins, B vitamins, vitamin E, and omega-3 fatty acids) showed no benefit on global cognitive or physical function in persons with mild to moderate dementia or MCI. Nonpharmacologic Interventions: We identified 61 trials (n=7,847) that evaluated nonpharmacologic patient-level interventions, including cognitive-focused, exercise, and multicomponent and other interventions. Among all interventions, there was no clear benefit on global or domain-specific measures of cognitive function compared with control conditions at 3 months to 2 years followup. Effect estimates generally favored the intervention groups over control groups, but the magnitude of effect was inconsistent across trials and represented very wide confidence intervals (ranging from no effect to a large effect). Physical function outcomes, including change in activities of daily living and independent activities of daily living, as well as quality of life and mental and neuropsychiatric symptoms, were inconsistently reported. There was, however, a pattern of effect for exercise interventions, with small improvements seen in measures of physical function and symptoms for intervention groups, whereas control groups reported worsening function. Caregiver and caregiver-patient dyad interventions including psychoeducation for the caregiver and care and case management interventions, reported in 88 trials (n=14,880), resulted in a consistent benefit on caregiver burden and depression outcomes. Effect sizes were mostly small, however, and were of unclear clinical significance. Little harm was evident in the few nonpharmacologic intervention trials that reported harms.
LIMITATIONS:
There is a lack of evidence around how screening for and treating MCI and early-stage dementia affects decision making outcomes. Furthermore, there has been little reproducibility in testing specific screening instruments in primary care populations. The treatment literature is limited by a lack of consistency in the specific outcomes reported and short followup duration. It is difficult to interpret the clinical importance of the small average effects seen among treatment trials, and many measures likely have limited responsiveness for patients with less pronounced cognitive impairment. Consistent and standardized reporting of results according to meaningful thresholds of clinical significance would be helpful in interpreting the small average effects on continuous outcome measures. Other important measures such as quality of life, physical function, and institutionalization, were inconsistently reported.
CONCLUSIONS:
Several brief screening instruments can adequately detect cognitive impairment, especially in populations with a higher prevalence of underlying dementia. There is no empiric evidence, however, that screening for cognitive impairment or early diagnosis of cognitive impairment improves patient, caregiver, family, or clinician decision making or other important outcomes nor causes harm. In general, there is support that AChEIs and memantine and interventions that support caregivers, including those that help coordinate care for patients and caregivers, can result in small improvements in the short term. Unfortunately, the average effects of these benefits are quite small and likely not of clinical significance. Any benefits are further limited by the commonly experienced side effects of medications and the limited availability of complex caregiver interventions. Cognitive stimulation and training, exercise interventions, and other medications and supplements showed some favorable effects on patients’ cognitive and physical function, but trial evidence lacked consistency and the estimates of benefit were imprecise. There is less evidence related to screening for and treating MCI. The test performance of the few instruments evaluated to detect MCI was lower than the sensitivity and specificity to detect dementia and there is little evidence for any pharmacologic or nonpharmacologic interventions to preserve or improve patient functioning in persons with MCI.
