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.
ANTECEDENTES: Omega-3 los ácidos grasos poliinsaturados (omega-3 PUFAs) a partir de fuentes vegetales y de pescado se consideran comúnmente como una alternativa no médica prometedora para mejorar las funciones del cerebro y retrasar la progresión de la demencia. Esta suposición se basa principalmente en los resultados de los estudios preclínicos y la investigación epidemiológica. Resultantes modelos explicativos apuntan al papel PUFAs omega-3 desempeñan en el desarrollo y la integridad de las neuronas del cerebro, su efecto antioxidante protector sobre las membranas celulares y los posibles mecanismos neuroquímicos relacionados directamente con la patología de Alzheimer específica. La investigación epidemiológica también encontró evidencia de la desnutrición en las personas con demencia. Teniendo en cuenta esto y el hecho de que los omega-3 PUFA no pueden ser sintetizados por los seres humanos, omega-3 PUFAs podría ser una opción de tratamiento prometedor para la demencia.
Evaluar la eficacia y seguridad de los suplementos de ácidos grasos poliinsaturados omega-3 (PUFA) para el tratamiento de las personas con demencia.
Métodos de búsqueda: Se realizaron búsquedas en el Registro Especializado del Grupo Cochrane de Demencia y Trastornos Cognitivos (ALOIS), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov y la Organización Mundial de la Salud (OMS) portal / ICTRP el 10 de diciembre de 2015. Se estableció contacto con los fabricantes de suplementos de omega-3 y examinaron las listas de referencias de los artículos señal y se incluyeron artículos.
Criterios de selección: Se incluyeron ensayos controlados aleatorios (ECA) en los que AGPI omega-3 en forma de suplementos o dietas enriquecidas fueron administrados a las personas con la enfermedad de Alzheimer (EA), demencia vascular (DV), la demencia con cuerpos de Lewy (DCL), demencia de la enfermedad de Parkinson (PDD) o la demencia frontotemporal (DFT).
Recopilación y análisis de datos: Las medidas de resultado primarias de interés fueron los cambios en las funciones cognitivas globales y específicos, el rendimiento funcional, gravedad de la demencia y los efectos adversos. Dos autores de la revisión seleccionaron de forma independiente los estudios, extrajeron los datos y evaluaron la calidad de los ensayos de acuerdo con el Manual Cochrane para las Revisiones Sistemáticas de Intervenciones. Hemos evaluado la calidad de las pruebas utilizando el sistema GRADE. Hemos recibido datos no publicados de los autores del ensayo y se recoge información de los efectos adversos de los artículos publicados. Hemos llevado a cabo meta-análisis para las medidas de resultado disponibles a los seis meses.
Resultados principales: Se incluyeron tres ensayos comparables aleatorios, controlados con placebo que investigan los suplementos de ácidos grasos omega-3 PUFA en 632 participantes con Alzheimer de leve a moderada durante seis, 12 y 18 meses. No se encontraron estudios que investigan otros tipos de demencia. Todos los ensayos eran de alta calidad metodológica. La calidad general de las pruebas para la mayoría de los resultados era alta.No hubo evidencia de un beneficio de PUFAs omega-3 en la función cognitiva cuando se mide a seis meses con la Escala de Evaluación de la Enfermedad de Alzheimer - subescala cognitiva (diferencia de medias estandarizada (DME) -0,02, 95% intervalo de confianza (IC) del -0,19-,15 ; 566 participantes; 3 estudios, evidencia de alta calidad) o Mini-Mental State Examination (diferencia de medias (DM) 0,18; IC del 95% -1.05 a la 1,41; 202 participantes, 2 estudios, pruebas de alta calidad) o sobre las actividades de la vida diaria ( DME -0,02; IC del 95%: -0,19 a 0,16; 544 participantes, 2 estudios, pruebas de alta calidad). También hubo ningún efecto a los seis meses de tratamiento en la gravedad de la demencia medida con el Clinical Dementia Rating - Suma de las cajas (DM -0,00; IC del 95% -0.58 a la 0,57; 542 participantes, 2 estudios, pruebas de alta calidad) o en la calidad de vida medida con la escala de calidad de vida en la Enfermedad de Alzheimer (DM -0,10; IC del 95% -1.28 a la 1,08; 322 participantes; 1 estudio; pruebas de alta calidad). No hubo diferencias a los seis meses sobre la salud mental medido con la valoración de la depresión de Montgomery-Asberg (DM -0,10; IC del 95%: -0,74 a la: 0.54; 178 participantes: 1 estudio, calidad de evidencia alta) o el Inventario Neuropsiquiátrico (DME 0,10 , IC del 95%: -0,07 a la 0,27; 543 participantes, 2 estudios, calidad de evidencia alta). Un estudio muy pequeño mostró un beneficio para los PUFAs omega-3 en las actividades instrumentales de la vida diaria después de 12 meses de tratamiento (DM -3,50; IC del 95%: -4,30 a -2,70; 22 participantes; pruebas de calidad moderada). Los estudios incluidos no midieron la función cognitiva específica. Los estudios no informaron eventos adversos también. Dos estudios indicaron que todos los eventos adversos fueron leves y que no difieren en frecuencia global entre los omega-3 PUFA y el grupo placebo. Los datos de un estudio no mostró diferencias entre los grupos en la frecuencia de eventos adversos (riesgo relativo (RR) 1,02; IC del 95%: 0,95 a 1,10; 402 participantes; 1 estudio; pruebas de calidad moderada) o cualquier evento adverso grave (RR 1.05, 95 % IC 0,78 a la 1,41; 402 participantes; 1 estudio, pruebas de alta calidad) a los 18 meses de tratamiento.
Conclusiones de los autores No se encontraron pruebas convincentes de la eficacia de los suplementos de ácidos grasos omega-3 PUFA en el tratamiento de Alzheimer de leve a moderada. Este resultado fue consistente para todos los resultados relevantes para las personas con demencia. Los efectos adversos de PUFAs omega-3 parecen ser bajos, pero en base a la evidencia sintetizada en esta revisión, no puede hacer una declaración final sobre la tolerabilidad. Los efectos sobre otras poblaciones no están claros.
El deterioro neurocognitivo debido a la enfermedad de Alzheimer (anteriormente denominado demencia de Alzheimer) (AD) es la forma más común de deterioro cognitivo en todo el mundo. Dado el aumento previsto de la población de 65 años o más, se prevé que la prevalencia de personas con EA aumentará exponencialmente durante los próximos 30 años. Los síntomas neuropsiquiátricos no cognitivos (SNP) ocurren comúnmente en la EA y se asocian con resultados adversos para los pacientes y sus cuidadores. Esta revisión resume ensayos controlados aleatorios (ECA) publicados entre 2004 y 2014 con una medida de resultado primaria de cambio en la gravedad de los síntomas para NPS en la EA. De los 388 artículos identificados inicialmente mediante una búsqueda bibliográfica, 33 ensayos cumplieron los criterios de inclusión. Quince de estos estudios tenían agitación / agresión como un síntoma objetivo. Veintiocho evaluaron tratamientos farmacológicos, incluyendo psicotrópicos, potenciadores cognitivos, estimulantes y nutracéuticos. Las intervenciones no farmacológicas incluyeron luz brillante, música, ejercicio y terapias de estimulación cognitiva. Entre las intervenciones farmacológicas, la eficacia modesta se informó con aripiprazol, citalopram, trazodona, metilfenidato, y analgésicos programados. Se observó una reducción significativa en la gravedad de los síntomas con casi todas las intervenciones no farmacológicas. Las variaciones en la metodología como los criterios de inclusión, el establecimiento del estudio y las medidas de resultado limitan la generalización de estos resultados. Las barreras a la implementación de intervenciones no farmacológicas en entornos clínicos incluyen limitaciones de recursos y capacitación. La terapia electroconvulsiva y el dronabinol son prometedores como estrategias de tratamiento emergentes. Se necesitan ensayos clínicos aleatorios para validar la utilidad de la terapia electroconvulsiva y el dronabinol, incluyendo dónde y con quién estas intervenciones resultarán más valiosas. (PsycINFO Database Record (c) 2016 APA, todos los derechos reservados)
ANTECEDENTES: A pesar de los ácidos grasos poliinsaturados (PUFA) de suplementos de omega-3 en pacientes deprimidos se han sugerido para mejorar la sintomatología depresiva, los resultados anteriores no son unívocas.
OBJETIVOS: Llevar a cabo un meta-análisis actualizado de los ensayos controlados aleatorios (ECA) de ácidos grasos omega-3 PUFA tratamiento de los trastornos depresivos, teniendo en cuenta las diferencias clínicas entre los pacientes incluidos en los estudios.
MÉTODOS: Se realizó una búsqueda en MEDLINE, EMBASE, PsycINFO, y la Base de Datos Cochrane de ECA utilizando AGPI omega-3 en pacientes con síntomas depresivos publicados hasta agosto de 2013. Diferencia de medias estandarizada en la medida clínica de la gravedad de la depresión era resultado primario. También se examinó Tipo de omega-3 utilizado (en particular el ácido eicosapentaenoico [EPA] y ácido docosahexaenoico [DHA]) y omega-3 como mono- o terapia adyuvante. Los análisis de meta-regresión evaluó los efectos del tamaño del estudio, la gravedad de la depresión de línea de base, la duración del ensayo, la dosis de ácidos grasos omega-3, y la edad de los pacientes.
RESULTADOS: Meta-análisis de 11 ensayos realizados y 8 respectivamente en los pacientes con un diagnóstico definido por el DSM de trastorno depresivo mayor (TDM) y los pacientes con sintomatología depresiva, pero sin diagnóstico de MDD demostraron un beneficio clínico significativo del tratamiento AGPI omega-3 en comparación con el placebo (diferencia estandarizada en modelo de efectos aleatorios 0,56 SD [IC del 95%: 0,20, 0,92] y 0,22 SD [IC del 95%: 0,01, 0,43], respectivamente; el análisis combinado fue 0,38 SD [IC del 95%: 0,18; 0,59]). El uso de la EPA sobre todo dentro de la preparación, en lugar de DHA, influenciado eficacia clínica final. Eficacia clínica significativa tenía el uso de ácidos grasos omega-3 PUFA como adyuvante en lugar de mono-terapia. No se encontró relación entre la eficacia y el estudio del tamaño, la gravedad de la depresión de línea de base, la duración del ensayo, la edad de los pacientes, y la calidad del estudio. Omega-3 PUFA resultó eficaz en la ECA en pacientes con trastorno bipolar, mientras que no se encontró evidencia para aquellos que viajan a su eficacia sobre los síntomas depresivos en la población joven, la depresión perinatal, enfermedad primaria distinta de la depresión y los sujetos sanos.
CONCLUSIONES: El uso de AGPI omega-3 es eficaz en pacientes con diagnóstico de trastorno depresivo mayor y en pacientes depresivos sin diagnóstico de trastorno depresivo mayor.
Resumen: El papel de la nutrición en la modulación de la enfermedad de Alzheimer (EA) sigue siendo incierto. Las personas que ingieren una dieta de tipo mediterráneo parecen ser menos propensas a desarrollar Alzheimer. Epidemiológicamente, combinaciones de alimentos ricos en vitaminas antioxidantes reducen el riesgo de AD. Fórmulas de combinación (por ejemplo, Souvenaid) parecen tener pequeños efectos sobre la cognición. Los suplementos de vitamina B eran en su mayoría decepcionante, con resultados contradictorios, salvo en los países donde el pan no está fortificada con ácido fólico. Eran generalmente negativa, al igual que los estudios de investigación de suplementos de ácidos grasos omega-3. Sobre la base de esta revisión, una dieta mediterránea y / o un suplemento de combinación, como Souvenaid, parecen ser los enfoques más beneficiosas con los posibles efectos adversos menos a frenar la progresión de la EA.
ANTECEDENTES: El debate sobre el papel de n-3 de cadena larga de ácidos grasos poliinsaturados (AGPI n-3) en el estado de ánimo depresivo continúa.
OBJETIVO: El objetivo fue actualizar una revisión sistemática anterior y meta-análisis de ensayos controlados aleatorios publicados que investigan los efectos de n-3 PUFAs en el estado de ánimo deprimido y explorar posibles fuentes de heterogeneidad.
Diseño: Ocho bases de datos en busca de ensayos que los participantes asignados al azar para recibir n-3 PUFAs o pescado, del estado de ánimo medida deprimida, que se utilizan participantes humanos, e incluyó un grupo de comparación a abril de 2009.
RESULTADOS: Treinta y cinco ensayos controlados aleatorios se identificaron 17 no se incluyeron en la revisión anterior. La diferencia combinada estandarizada en los resultados promedio de los 29 ensayos que proporcionaron datos para permitir la puesta en común (modelo de efectos fijos) fue de 0,10 SD (95% IC: 0,02, 0,17) en aquellos que recibieron n-3 PUFAs frente a placebo, con una fuerte evidencia de heterogeneidad (I (2) = 65%, P <0,01). La presencia de gráfico en embudo asimetría sugiere que el sesgo de publicación es una fuente probable de esta heterogeneidad. La gravedad de los síntomas depresivos y el diagnóstico de los participantes también explicó parte de la heterogeneidad observada. Mayores efectos de n-3 PUFAs se encontraron en los individuos con síntomas depresivos más severos. En los ensayos que incluyeron a personas con un trastorno depresivo diagnosticado, la diferencia media combinada fue 0,41 (IC 95%: 0,26 a 0,55), aunque la evidencia de la heterogeneidad también se encontró (I (2) = 71%). En los ensayos que reclutaron a personas sin un diagnóstico de depresión, sin efectos beneficiosos de los n-3 PUFAs se encontraron (la más grande diferencia combinada media: 0,22, IC 95%: -0,01 a 0,44; I (2) = 0%).
CONCLUSIONES: La evidencia de prueba de los efectos de la n-3 PUFAs en estado de ánimo depresivo ha aumentado, pero sigue siendo difícil de resumir debido a la heterogeneidad considerable. La evidencia disponible ofrece una cierta ayuda de un beneficio de n-3 PUFAs en personas con depresión diagnosticada, pero no hay evidencia de algún beneficio en personas sin un diagnóstico de la enfermedad depresiva.
Around one in four people suffer from mental illness at some stage in their lifetime. There is increasing awareness of the importance of nutrition, particularly omega-3 polyunsaturated fatty acids (n-3 PUFA), for optimal brain development and function. Hence in recent decades, researchers have explored effects of n-3 PUFA on mental health problems over the lifespan, from developmental disorders in childhood, to depression, aggression, and schizophrenia in adulthood, and cognitive decline, dementia and Alzheimer's disease in late adulthood. This review provides an updated overview of the published and the registered clinical trials that investigate effects of n-3 PUFA supplementation on mental health and behavior, highlighting methodological differences and issues.
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.
