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. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: 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. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: The efficacy of cognition-focused interventions (CFIs) for the treatment of Alzheimer's disease (AD) has been questioned recently. To date, the specific effects of cognitive rehabilitation (CR), cognitive training (CT), and cognitive stimulation [CS] have not been analyzed due to inconsistencies in the use of the comparison groups. This work aims to analyze the differential effects of CFIs by removing the influence of the comparison group from the estimates of the effects.
METHOD: a literature search performed in Pubmed, Proquest, and Embase databases yielded 65 potential studies, of which 33 studies with a sample size of 1,225 individuals were meta-analyzed. Each intervention group was treated as the unit of analysis to remove the confounding effects of the comparison condition. Measures of general cognitive functioning, memory and functional outcomes were compared using the hierarchical robust variance estimator metaregression. Age, education, sex, risk of bias, sample size, duration of intervention, the proportion of drop-outs, pharmacological treatment, and severity of disease were included as covariates.
RESULTS: Only CT differed from no cognition-focused interventions (NCFI) for memory outcomes in univariate analyses, but differences became nonsignificant when covariates were included in the model. CR showed a significantly higher effect in outcomes measuring functioning in targeted domains with no differences in standard cognitive tests relative to NCFI.
CONCLUSIONS: This work supports previous findings questioning the efficacy of CT or CS for AD. Moving toward CFIs focused on relevant goals and including measures related to the skills, abilities or activities that are the focus of the intervention is encouraged. (PsycINFO Database Record
OBJECTIVE: The goal of the evidence review was to evaluate the effectiveness of interventions for caregivers of people with Alzheimer's disease and related major neurocognitive disorders that facilitate the ability to maintain participation in the caregiver role.
METHOD: Scientific literature published in English between January 2006 and April 2014 was reviewed. Databases included MEDLINE, PsycINFO, CINAHL, OTseeker, and the Cochrane Database of Systematic Reviews.
RESULTS: Of 2,476 records screened, 43 studies met inclusion criteria. Strong evidence shows that multicomponent psychoeducational interventions improve caregiver quality of life (QOL), confidence, and self-efficacy and reduce burden; cognitive reframing reduces caregiver anxiety, depression, and stress; communication skills training improves caregiver skill and QOL in persons with dementia; mindfulness-based training improves caregiver mental health and reduces stress and burden; and professionally led support groups enhance caregiver QOL.
CONCLUSION: Strong evidence exists for a spectrum of caregiver interventions. Translation of effective interventions into practice and evaluation of sustainability is necessary.
OBJECTIVES: To investigate the effects on carer well-being of carer involvement in cognition-based interventions (CBIs) for people with dementia. METHODS: A review and meta-analysis were performed. We searched electronic databases for randomised controlled trials (RCTs). Two reviewers worked independently to select trials, extract data and assess the risk of bias. RESULTS: A total of 4737 studies was identified. Eight RCTs met the inclusion criteria. Only seven studies with 803 dyads of people with dementia and carers were included in the meta-analysis. Evidence indicated that carer involvement in CBIs for people with dementia had a beneficial effect on carers’ quality of life with effect size Hedges’ <i>g</i> = 0.22; 95% confidence interval of 0.02 to 0.42, <i>z</i> = 2.19 and <i>p</i> = 0.03. Carers’ depression levels were reduced in the intervention group with effect size Hedges’ <i>g</i> = 0.17; 95% confidence interval of 0.02 to 0.32, <i>z</i> = 2.19 and <i>p</i> = 0.03. No significant differences were observed in levels of anxiety symptoms, caregiving relationship and carer burden in the intervention group compared to those in the control group. CONCLUSION: Because CBIs are designed to deliver benefit for people with dementia, the collateral benefits for carers have potential implications for the importance of CBIs in service delivery and may contribute to cost effectiveness. However, there remains a lack of quality of research in this area. Particularly, in some outcomes, there was a lack of consistency of results, so the findings should be interpreted with caution. Future studies of the impact of CBIs on carers with larger samples and high-quality RCTs are warranted. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
IMPORTANCE: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes.
OBJECTIVE: To inform how payers and providers should identify patients with "advanced illness" and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system.
EVIDENCE REVIEW: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015).
RESULTS: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10).
CONCLUSIONS: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited.
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.
