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Information about ongoing health services research and public health projects
| Diagnosis and treatment of clinical Alzheimer's-type dementia (CATD) | |
|---|---|
| Investigator (PI): | Brasure, Michelle; Wilt, Tim; Butler, Mary; McCarten, J Riley; Hemmy, Laura; Dysken, Maurice; Talley, Kristine; Forte, Mary; Taylor, Brent; Greer, Nancy; McDonald, Rod; Desai, Priyanka; Linskens, Eric; Miller, Margaret; Silverman, Sarah; Nelson, Victoria; Ng, Weiwen |
| Performing Organization (PO): |
(Current): Minneapolis VA Health Care System / (612) 725-2000 |
| Supporting Agency (SA): | Agency for Healthcare Research and Quality (AHRQ) |
| Initial Year: | 2018 |
| Final Year: | 2019 |
| Record Source/Award ID: | PROSPERO/CRD42018117897 |
| Award Type: | Contract |
| Award Information: | Reports resulting from this project |
| Abstract: | Review question: Abbreviated key questions (KQs): KQ 1: In adults with clinical Alzheimer's-type dementia (CATD), what are the efficacy and harms of prescription pharmacological interventions versus placebo/inactive control for treatment of cognition, function, and quality of life? KQ 2: In adults with CATD, what are the efficacy and harms of nonprescription pharmacological interventions versus placebo/inactive control for treatment of cognition, function, and quality of life? KQ 3: In adults with CATD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus other active interventions for treatment of cognition, function, and quality of life? KQ 4: In adults with CATD and behavioural and psychological symptoms of dementia (BPSD), what are the efficacy and harms of prescription pharmacological interventions versus placebo/inactive control for treatment of BPSD? KQ 5: In adults with CATD and BPSD, what are the efficacy and harms of nonprescription pharmacological interventions versus placebo/inactive control for treatment of BPSD in adults with CATD and BPSD? KQ 6: In adults with CATD and BPSD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus other active interventions for treatment of BPSD? KQ 7: In adults with suspected CATD, what are the accuracy, comparative accuracy, and harms of different individual cognitive diagnostic tests and their combinations for making the diagnosis of CATD as defined by full clinical evaluation and/or neuropsychological testing with explicit diagnostic criteria? KQ 8: In adults with a clinical diagnosis of CATD, what are the accuracy, comparative accuracy, and harms of brain imaging, cerebrospinal fluid (CSF), and blood tests for diagnosing pathologically confirmed Alzheimer's disease as the underlying etiology? Searches: Electronic database searches: We will search Ovid MEDLINE, Ovid Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs), nonrandomized controlled clinical trials (CCTs), observational studies, and systematic reviews published and indexed in these bibliographic databases. The search algorithm will include relevant controlled vocabulary and natural language terms for the concepts of Alzheimer's disease, dementia, biomarkers, and diagnostic accuracy, and will be combined with validated filters to select study designs. We will supplement our electronic database searching with backward citation searches of included studies and of highly relevant recent systematic reviews. Searches were conducted in June and July of 2018 and will be updated in the spring of 2019. Treatment search dates were from year of database origination. Diagnosis using cognitive testing search dates were from year of database origination. Diagnosis using biomarkers search dates were from 2012 and supplemented with hand searching to identify older studies. Types of study to be included: Treatment: RCTs or CCTs or systematic reviews will be included. Diagnosis: Cohort studies or systematic reviews will be included. Condition or domain being studied: The condition is clinical Alzheimer's-type dementia (CATD). Participants/population: The study population is individuals with clinical Alzheimer's-type dementia. Intervention(s), exposure(s): Treatment: These will be select pharmacologic interventions and supplements. Diagnosis: These will be cognitive testing or biomarker values. Comparator(s)/control: Treatment: This will be placebo or active comparator. Diagnosis: Cognitive testing--this will be normal cognition adults/other dementia. Diagnosis: Biomarkers--this will be autopsy diagnosis. Context: Treatment: This will be community-dwelling, assisted living, and nursing home. Diagnosis: This will be community-dwelling, and assisted living. Main outcome(s): Treatment: The outcomes are change in patient cognition (global screen, multidomain, memory, executive function, language, attention), function, or quality of life (QoL) on validated test; change in disease stage based on validated test; change in patient "at home" instrumental activities of daily living (IADL) or activities of daily living (ADL) function; change in patient residence to different level of independence; change in the frequency and/or severity of patient behavioural and psychological symptoms of dementia (BPSD) on validated tests; agitation/aggression; psychosis; depression; anxiety; disinhibited sexual behavior; change in patient QoL on validated test; and change in validated general behavior scale. Timing and effect measures: These are, for treatment: cognition, function, QoL, general behavior, depression, anxiety: 24 weeks; for treatment: agitation, aggression, psychosis, disinhibited sexual behavior: 2 weeks; and for diagnosis: no time limit. Additional outcome(s): For treatment, additional outcomes are change in caregiver/staff outcomes on validated tests (depression, global stress/distress, QOL, burden). Timing and effect measures: 24 weeks. Data extraction (selection and coding): Study selection: Titles and abstracts will be reviewed by two independent investigators to identify studies meeting eligibility criteria. Studies considered ineligible by both investigators will be excluded, while those considered potentially eligible by at least one of these investigators will be forwarded for full text screening. All studies forwarded for full-text screening will be independently evaluated by two investigators to determine if inclusion criteria are met and, if excluded, to determine the reason(s) for exclusion. Differences in screening decisions will be resolved by consultation between investigators, and, if necessary, consultation with a third investigator. Systematic reviews determined to be high quality may be used to replace de novo data extraction processes for specific population/treatment/outcome comparisons that are sufficiently relevant. Data extraction: For all eligible studies, one investigator will extract selected data and a second reviewer will check the accuracy of extracted data. Studies determined to be high risk of bias will have only limited data extracted. Studies judged to have low to moderate risk of bias will undergo additional data extraction. Fields that will be extracted from all studies will include participant eligibility criteria, setting, and participant baseline characteristics (age, race/ethnicity, sex, depression, and pretreatment/pretesting cognitive and functional level/CATD stage). Additional fields to be extracted from intervention studies are intervention details (drug class, name, dose and delivery route), control intervention details, follow-up duration, living setting, outcomes (cognitive [global screen, global multidomain, memory, executive, language, attention], functional, quality of life, and behavioral symptoms), and harms. Additional fields to be extracted from diagnostic studies are participant sampling and recruitment details; prevalence of reference condition; index test and cut-off values used to categorize participants; reference standard and methods of time interval between measurements of index and reference test; and sensitivity, specificity, true positives, true negatives, false positives, and false negatives. Risk of bias (quality) assessment: Two investigators will independently assess each study for bias in several different domains, and then, considering these assessments, also rate its overall risk of bias. For individual CATD treatment studies, for each outcome of interest (i.e., stage, global cognition and cognition domains, function, quality of life, and BPSD symptoms), risk of bias for each of the following domains will be rated as high, medium, or low using a risk of bias tool: selection bias, attrition bias, detection bias, performance bias, and reporting bias. For diagnosis test studies, for each test of interest (e.g., brief cognitive tests, biomarkers), risk of bias for each of the following domains will be rated as high, low, or unclear using the QUADAS-2 tool (Quality Assessment of Diagnostic Accuracy Studies): patient selection, index test, reference standard, and flow and timing. Each investigator will independently rate overall study risk of bias as high, medium, or low. Investigators will consult to reconcile any discrepancies in risk of bias ratings for individual domains and overall. Strategy for data synthesis: Results will be organized first by key question. Then, for key questions 1-3, results will be organized by treatment comparison, and then by targeted treatment outcome (disease stage, cognition [global screen, global multidomain, memory, executive, language, attention], function, quality of life) and harms. Similarly, for key questions 4-6, results will be organized by treatment comparison, and then by targeted treatment outcome (agitation/aggression, psychosis, depression, anxiety, disinhibited sexual behavior, general behavior) and harms. For key questions 7-8, results will be organized by diagnostic test category (cognitive, brain imaging, cerebrospinal fluid [CSF], blood), and by specific test, and then by outcomes and harms. For treatment studies, we will prioritize analyses of outcomes framed as responders, or improved or stable versus declined, or meeting an a priori established threshold for a clinically meaningful improvement. We will calculate risk ratios and absolute risk differences with the corresponding 95 percent confidence intervals (CIs). For continuous outcomes, we will calculate weighted mean differences and/or standardized mean differences with the corresponding 95 percent CIs. For diagnostic test studies, we will report/calculate sensitivity, specificity, positive and negative likelihood ratios and their 95 percent confidence intervals for each population and combination of index and reference test thresholds. We will assess individual study clinical and methodological heterogeneity to determine appropriateness of pooling data. When we judge that data are appropriate for pooling, we will synthesize data using a generalized linear mixed model approach. If the analyses yield substantial heterogeneity, we will stratify the results to assess treatment outcomes and diagnostic accuracy, respectively, based on patient or study characteristics and/or explore sensitivity analysis. When data allow, we will perform stratified analyses to evaluate a priori selected possible effect modifiers of CATD treatment efficacy, comparative effectiveness, and cognitive and biomarker testing diagnostic accuracy, comparative accuracy, and harms. Analysis of subgroups or subsets: When data allow, we will perform stratified analyses to evaluate a priori selected possible effect modifiers of CATD treatment efficacy, comparative effectiveness, and cognitive and biomarker testing diagnostic accuracy, comparative accuracy, and harms. For all key questions, we will examine age, sex, race/ethnicity, depression, and pretreatment cognitive or functional status/CATD stage. For KQs 4-6 only, we will examine pretreatment BPSD severity. For KQs 1-6 only, we will examine living setting. For KQs 7-8 only, we will examine education. We will record whether the possible effect modifiers were identified a priori. In addition, we will examine if treatment efficacy differs as a function of drug dose, treatment duration, and treatment follow-up duration, and if diagnostic accuracy differs as a function of the time interval between diagnostic test measurement and the determination of the reference diagnosis. |
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| Country: | United States |
| State: | Minnesota |
| Zip Code: | 55417 |
| UI: | 20192151 |
| Project Status: | Completed |
| Record History: | ('Project contact: Howard Fink: howard.fink@va.gov',) |
