Preventing and Treating Dementia: Research Priorities to Accelerate Progress (2025)
Chapter: Appendix A: Scoping Review Methods
Appendix A
Scoping Review Methods
The committee was asked to examine and assess the current state of biomedical research related to Alzheimer’s disease and related dementias (AD/ADRD), including evidence on interventions aimed at preventing, delaying, and treating AD/ADRD. This appendix presents the rationale and methods for a scoping review of published systematic reviews that aided the committee in addressing this element of its Statement of Task. A systematic review of the recent primary literature was not feasible given the available time and budget. The use of previously published systematic reviews was useful for developing an overarching view of the landscape of AD/ADRD intervention research; however, the committee acknowledges the potential for biases and the inherent limitations of this approach. These include the potential for a compounding of biases from individual systematic reviews (e.g., accumulation of publication and selection biases), variation in the quality of the included reviews, variation in the quality of primary literature included in those systematic reviews, overlap in the primary studies included, and inclusion of outdated information (Ballard and Montgomery, 2017). Additionally, because a limited number of systematic reviews were selected for the scoping review and given the potential lag between publication of primary studies and the conduct of systematic reviews synthesizing the body of evidence, the failure to identify a systematic review for a given intervention or population may not indicate a lack of primary evidence. This represents an important limitation when using a scoping review of existing systematic reviews for a gap analysis.
To the extent possible, the review protocol sought to directly address some of these limitations. However, for these reasons, the committee
determined that the scoping review would not be appropriate for drawing conclusions on the effectiveness of a given intervention. Importantly, this exercise does not represent the entirety of the research efforts included in the report, which is the product of extensive literature searches, input from experts in public sessions, feedback from the public, and committee expertise. The findings from the scoping review were used to inform the committee’s description of the research landscape and provide some evidence on emerging and established pharmacological and nonpharmacological interventions described in Chapter 4. Details about the articles included and excluded from the scoping review and more details about the methods used to carry out the scoping review can be found below.
RATIONALE AND OBJECTIVES
Recent approvals of three therapeutics to treat Alzheimer’s disease (AD) have increased optimism that the tremendous investment in research for AD/ADRD over the last decade may be yielding tangible returns. Despite this optimism, these therapies come with high costs and significant risks and may provide modest benefits to only a small proportion of the millions of people living with AD in the United States. There remains a clear need for the development of a broader array of effective interventions to prevent, delay, and treat AD/ADRD across the entirety of the population. This scoping review included recently published systematic reviews to identify current gaps in research related to interventions for preventing, delaying, and treating AD/ADRD. Tools for screening and diagnosis of AD/ADRD were not included in this review of interventions. The understanding of the AD/ADRD research landscape afforded by the scoping review supported the development of the committee’s conclusions and recommendations for priority research areas and the creation of scientific research questions that could be addressed by the National Institutes of Health in the next 3–10 years.
The primary objective of this review was to evaluate the recent research landscape for gaps and develop an understanding of the state of the evidence for interventions for the prevention, delay, or treatment of AD/ADRD and the limitations of that evidence. The review considered interventions across three categories: pharmacological, nonpharmacological, and combinations of both. Research of interest for this review included studies in humans that are focused on interventions to prevent, delay, or treat AD/ADRD. Owing to the complex nature of AD/ADRD and the breadth of conditions involved, the population of interest included all individuals who are currently living with AD or a related dementia and individuals who are at risk of AD/ADRD (all individuals who expect to reach older age). Interventions of interest included those
aimed at preventing AD/ADRD from developing and treatments aimed at delaying the onset or slowing or halting the progression of AD/ADRD. Articles not of interest to this review included research conducted using animal or in vitro models, research on neurodegenerative diseases outside of the scope of the committee’s work, and research on the care of people living with dementia and interventions for caregivers and care partners. More detailed information on inclusion and exclusion criteria, as well as the operational process for carrying out the steps of the review, is described in the methods section below.
METHODS
All systematic reviews included in the scoping review were published between January 1, 2017, and February 20, 2024, written in English, and peer reviewed. The included systematic reviews focused on the assessment of an intervention (including individual- and population-level strategies) in human participants to prevent, delay, or slow AD/ADRD and included interventions that are pharmacological or nonpharmacological, as well as combinations of both.
Articles were excluded if they did not meet the criteria listed above. This included articles that do not assess the effectiveness of an intervention in humans and articles classified as perspectives or opinions or as conference papers. Articles were excluded if they exclusively focused on conditions and outcomes unrelated to the defined dementia types within the scope of the committee’s work. Excluded neurodegenerative conditions and their associated outcomes included dementia related to human immunodeficiency virus/acquired immunodeficiency syndrome, dementia as a result of traumatic brain injury, dementia as a result of incident stroke (although vascular contributions to dementia are included), Huntington’s disease, amyotrophic lateral sclerosis, multiple system atrophy, and Parkinson’s disease. Importantly, all articles solely focused on care partners and caregivers as the population of interest or on outcomes associated with caregivers (e.g., depression or anxiety in caregivers) were excluded as these outcomes are outside the committee’s charge. In accordance with the Statement of Task, articles focused on care interventions (e.g., care coordination, pain management) were also excluded.
The following definitions were used:
- AD/ADRD, for the purposes of the committee’s report, includes all causes of neurodegeneration that are included in the study scope, including AD, Lewy body dementia (LBD), frontotemporal dementia (FTD), limbic-predominant age-related TDP-43 encephalopathy, vascular dementia, and multiple etiology dementia.
- Dementia is an umbrella term used to describe the grouping of neurodegenerative disorders included within the study scope.
- Clinical dementia is impairment that meets the clinical criteria for a diagnosis of dementia.
- Mild cognitive impairment is a status that denotes a level of deterioration from normal cognitive function that is identifiable (e.g., by the individuals themselves, close contacts, or clinicians) but that does not significantly impair functions related to activities of daily living.
- Intervention refers to any program or treatment applied to an individual or at a population level (whether pharmacological or not) that is designed to prevent or modify the condition under investigation. These can include interventions aimed at the prevention or delay of onset and are not limited to pharmacological treatments. Interventions may also include nonpharmacological neuroprotective strategies implemented at any stage in the life course to prevent pathophysiologic processes. Given the current incomplete neurobiological understanding of AD/ADRD, the distinction between interventions that prevent, delay, and treat cognitive decline and interventions to prevent and treat neuropsychiatric symptoms may not be as clear as may be assumed.
- Cognitive outcomes include changes that can be measured in the brain and are associated with impaired cognition that can be perceived by the person living with the condition and their loved ones. Cognitive outcomes can include changes in language processing and use, attention, executive function, and visual perception that can be identified with cognitive tests, as well as intermediate outcome measures, such as biomarkers (e.g., amyloid, tau).
- Functional outcomes include changes in an individual’s physical or social function in their daily living. These outcomes can be conceptualized as the ability to perform self-care, self-maintenance, and daily physical activities. Common measures include activities of daily living, which include basic, daily tasks, and instrumental activities of daily living. Examples of some measurable functional outcomes include mobility (e.g., gait, risk of falls), personal hygiene (e.g., ability to bathe and use the toilet), dressing, preparing meals and feeding, using transportation, managing finances, using communication devices, and managing medications.
- Neuropsychiatric, behavioral, and quality-of-life outcomes include those noncognitive core features of AD/ADRD that are included within the diagnostic criteria for these conditions. The severity of these symptoms is often used as outcome measures and may include aggression, challenging or unpredictable behavior, agitation,
- personality changes/mood, sleep changes and disruptions, apathy, anxiety, insecurity, hallucinations, delusions/other psychotic behavior, disinhibition, and depression, among others.
- Systematic review is a review of a clearly formulated question that uses systematic and explicit methods to identify, select, and critically appraise relevant research, and to collect and analyze data from the studies that are included in the review. Statistical methods (meta-analysis) may or may not be used to analyze and summarize the results of the included studies.
Information Sources, Search, and Screening
To identify articles meeting the inclusion criteria of the scoping review, PubMed and Embase were searched for articles published between January 2017 and January 2024. This search was carried out on February 20, 2024. Search strategies were drafted by National Academies program staff based on committee-developed search terms and criteria and were reviewed by a trained research librarian. Search results from both databases were imported into PICO Portal and duplicates were removed.
Two National Academies staff members performed the initial title/abstract screening, beginning in February 2024, with one staff member serving as the adjudicator for any records for which inclusion or exclusion was unclear. The first 50 abstracts went through dual review to test and calibrate the screening process, and the remainder of the abstracts were divided among the two reviewers for a single reviewer title/abstract screening. The 824 records included after title/abstract screening were then passed to the PICO Portal team, a consulting group contracted by the committee, for full-text review and quality assessment.
Quality Assessment and Systematic Review Selection Process
The review selection process was developed in consultation with the PICO Portal team, which included consultants from evidence-based practice centers. The selection process sought to bring to the attention of the committee the most current and high-quality reviews by identifying the presence or absence of key methodological characteristics as determined through a series of questions. This simplified quality assessment process confirmed whether the article represents a true systematic review and that a minimum set of quality criteria were met (see Box A-1). The PICO Portal consultant team then provided those articles that met these quality criteria to the National Academies team for further assessment and selection. Articles meeting the criteria were organized by dementia type (e.g., LBD, FTD, AD), outcomes assessed, and intervention type to facilitate the selection
BOX A-1
Overview of Quality Assessment Process
- Was >1 source searched?
- No, only one source was searched
- Yes, two or more sources were searched
- No information provided
- Was a named RoB tool used? (Did the study assess RoB of each individual study with a named tool?) (If answered “No” for Q1, please skip this question and subsequent ones)
- No. A named RoB tool was not used to assess each study.
- Yes. A named RoB tool was used to assess each study.
- No information provided
- Was protocol registered? (Was the protocol used for this systematic review prepublished or registered? Please enter a registration # in the Notes field if provided.) (If answered “No” for Q1 or Q2, please skip this question.)
- No
- Yes
- Latest search date
This information will be entered as text: [Year-Month-Day]
NOTE: RoB = risk of bias
of the recent, high-quality reviews representing the current research landscape for inclusion in the scoping review. Additionally, primary research articles included in the systematic reviews were compared to limit overlap where possible. Sixty-five articles were ultimately selected for data extraction, which represented a spectrum of different interventions and types of dementia. The PICO Portal then completed the data extraction from these selected articles.
SCOPING REVIEW ANALYSIS
Descriptive summaries of the 65 articles included in the scoping review are presented in Tables A-1 and A-2 for pharmacological and nonpharmacological interventions, respectively (systematic reviews that included both nonpharmacological and pharmacological interventions are indicated in the tables). The systematic reviews were used in the development of a gap analysis related to the current state of the evidence on interventions for preventing and treating AD/ADRD, which is presented
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Adesuyan et al., 2022 | 2001–2018 | Adults age 40 years or older with hypertension and normal cognition | 9 | Cohort studies; case–control studies |
| Battle et al., 2021 | 2002–2010 | Persons living with vascular dementia or other vascular cognitive impairment | 8 | RCTs |
| Blackman et al., 2021* | 1993–2020 | Persons living with MCI or mild to moderate AD dementia | 16 | RCTs; crossover trials; prospective cohort studies |
| Cardinali et al., 2021 | 1994–2019 | Postmenopausal women living with or at risk for AD | 25 | Controlled clinical trials; observational studies |
| Corasaniti et al., 2024* | 2011–2023 | Persons living with dementia of any etiology | 10 | Clinical trials; retrospective studies |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Prevention of AD |
Individual or combined antihypertensive agents:
|
| Cognitive function; functional outcomes |
Cholinesterase inhibitors:
|
| Neuropsychiatric and behavioral symptoms (sleep) |
Interventions to improve the duration or quality of sleep:
|
| Cognitive function; neuropsychiatric and behavioral symptoms; prevention of AD | Hormone therapy |
| Cognitive function; neuropsychiatric and behavioral symptoms |
Autophagy inducers:
|
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Cunningham et al., 2021 | 1991–2019 | Adults with hypertension without prior cerebrovascular disease | 12 | RCTs |
| Chu et al., 2021 | 1999–2019 | Persons living with DLB | 29 | RCTs; uncontrolled single-arm trials |
| Dallaire-Theroux et al., 2021 | 2010–2019 | Adults age 40 years or older with hypertension and without prior dementia diagnosis | 7 (5 completed and included in authors’ analysis) | RCTs |
| d’Angremont et al., 2023 | 2000–2016 | Persons living with AD and DLB | 19 (14 in AD and DLB populations) | RCTs |
| Ebell et al., 2024 | 2009–2023 | Persons living with cognitive impairment or AD, or at high risk for AD | 19 | RCTs |
| Gomez-Soria et al., 2023b | 2003–2021 | Adults over 65 years of age who are cognitively healthy or living with MCI or dementia | 30 | RCTs; nonrandomized controlled clinical trials; observational studies; pre-post studies |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Prevention of cognitive impairment or dementia |
Antihypertensive agents:
|
| Cognitive function; neuropsychiatric and behavioral symptoms | Aripiprazole; armodafinil; citalopram; donepezil; galantamine; levodopa; memantine; olanzapine; quetiapine; risperidone; rivastigmine; yokukansan; zonisamide |
| Prevention of cognitive decline, MCI, and dementia | Standard versus intensive blood pressure control |
| Neuropsychiatric and behavioral symptoms |
Cholinesterase inhibitors:
|
| Cognitive function; functional outcomes | Monoclonal antibodies targeting amyloid |
| Neuropsychiatric and behavioral symptoms; functional outcomes; quality of life | Cognitive stimulation, alone or in combination with acetylcholinesterase inhibitors |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Gómez-Soria et al., 2023a | 2003–2021 | Adults age 65 years or older who are cognitively healthy or living with MCI or dementia | 33 | RCTs; nonrandomized controlled clinical trials; observational studies; pre-post studies |
| Huang et al., 2023b | 1998–2018 | Persons living with dementia | 59 | RCTs |
| Huang et al., 2023a | 2003–2020 | Persons living with FTD | 7 | RCTs |
| Kitt et al., 2023 | 2007–2023 | Adults without prior dementia diagnosis | 11 | RCTs |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Cognitive function | Cognitive stimulation, alone or in combination with acetylcholinesterase inhibitors |
| Neuropsychiatric and behavioral symptoms |
Cognitive enhancers:
Antipsychotics:
Antidepressants:
Mood stabilizers:
|
| Neuropsychiatric and behavioral symptoms; cognitive function; functional outcomes | Oxytocin, trazodone, paroxetine, piracetam, memantine, tolcapone |
| Prevention of dementia or cognitive impairment | Antiplatelet therapy |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Kuate Defo et al., 2024 | 2011–2022 | Adults diagnosed with diabetes and without prior dementia diagnosis | 127 (27 primary studies included in authors’ quantitative analysis and 100 review articles included in authors’ qualitative review) | Cohort studies; case–control studies |
| Kwan et al., 2022 | 2014–2018 | Adults with cerebral small vessel disease and without prior dementia diagnosis | 3 | RCTs |
| Lyu et al., 2023 | 2003–2023 | Persons living with AD | 41 (35 with relevant outcomes) | RCTs |
| McShane et al., 2019 | 1991–2016 | Persons living with AD, vascular, mixed, or other types of dementia | 44 | RCTs |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Prevention of dementia |
Antidiabetic medications:
|
| Cognitive function; functional outcomes | Antithrombotic therapy |
| Cognitive function |
Anti-amyloid-β drugs including Active immunotherapy drugs:
Passive immunotherapy drugs:
Small-molecule drugs:
|
| Cognitive function; functional outcomes; neuropsychiatric and behavioral symptoms | Memantine |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Muhlbauer et al., 2021 | 1995–2020 | Persons living with AD, vascular dementia, or mixed dementia (AD and vascular) | 24 | RCTs |
| Nimmons et al., 2024* | 1982–2023 | Persons living with dementia | 31 | RCTs |
| Olmastroni et al., 2022 | 2000–2020 | Adults at risk for dementia | 46 | Cohort studies; case-control studies |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Neuropsychiatric and behavioral symptoms |
Typical antipsychotics:
Atypical antipsychotics:
|
| Neuropsychiatric and behavioral symptoms |
Nonpharmacological interventions:
Pharmacological interventions:
|
| Prevention of AD and dementia | Statins |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Profyri et al., 2022* | 1999–2021 | Persons living with severe dementia | 30 (23 not related to care or caregiver interventions) | RCTs |
| Sun et al., 2023 | 2001–2022 | Adults without prior dementia diagnosis | 6 | Cohort studies |
| Tao et al., 2024 | 1995–2023 | Adults at risk for dementia and AD | 22 | Cohort studies; cross-sectional studies; RCTs |
| Tedeschi et al., 2021 | 2018–2020 | Persons living with AD | 34 (2 using relevant [clinical] study design) | Clinical trials |
| Terao and Kodama, 2024 | 2013–2023 | Persons living with MCI and AD | 7 | RCTs |
| van Middelaar et al., 2018* | 1996–2017 | Adults without prior dementia diagnosis | 9 | RCTs |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Cognitive function; neuropsychiatric and behavioral symptoms; functional outcomes; mortality |
Nonpharmacological interventions:
Pharmacological interventions:
|
| Prevention of dementia | Influenza vaccination |
| Prevention of AD and dementia | Aspirin |
| Cognitive function | Gene therapy: Adeno-associated virus-nerve growth factor |
| Cognitive function |
Passive anti-amyloid beta immunotherapies:
Lithium |
| Prevention of all-cause dementia, AD, and vascular dementia |
Blood-pressure-lowering interventions:
Combination interventions |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Wang et al., 2022a | 2006–2021 | Persons living with AD or MCI | 16 | RCTs |
| Watts et al., 2023* | Persons living with DLB | 135** | RCTs; nonrandomized trials; open-label trials; longitudinal studies; case series; case reports | |
| Zhan et al., 2021* | 2003–2020 | Persons living with vascular cognitive impairment | 23 | RCTs |
| Zhang et al., 2022 | 2012–2021 | Persons living with dementia | 22 | RCTs |
| Zheng et al., 2022 | 2003–2021 | Persons living with mild to moderate cognitive impairment | 34 | RCTs |
*Indicates systematic review that assessed both nonpharmacological and pharmacological interventions.
a Publication date range for primary articles included in listed systematic reviews is only inclusive of primary articles relevant to the focus of this scoping review (population, intervention types, outcomes of interest).
b Populations listed are only those relevant to the focus of this scoping review (e.g., if primary studies included in a systematic review were focused on Parkinson’s dementia, that population was not described in the table).
c When a systematic review included primary studies that were not a focus of this scoping review (e.g., wrong population, care- or caregiver-focused interventions), the number of relevant included studies for that systematic review is provided in parentheses.
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Cognitive function, functional outcomes |
Hypoglycemic drugs:
|
| Cognitive function; neuropsychiatric and behavioral symptoms; mortality | Donepezil; rivastigmine; galantamine; memantine; modafinil/armodafinil; clozapine; quetiapine; risperidone; olanzapine; aripiprazole; dopamine antagonists; herbal medications (yokukasan, Feru-guard); ramelteon; clonazepam; antidepressants (citalopram, paroxetine) |
| Cognitive function; functional outcomes | Gingko biloba extract alone or in combination with pharmacologic treatments (donepezil, nimodipine, huperzine, oxiracetam, piracetam, butylphthalide, ergoloid mesylate) |
| Cognitive function; neuropsychiatric symptoms; functional outcomes | Magnesium valproate when used in conjunction with other dementia treatments (donepezil, galantamine, quetiapine, olanzapine, aripiprazole) |
| Cognitive function | Anti-tau drugs |
d Reported outcomes are only those noted by the systematic review authors as primary outcomes and relevant to the focus of this scoping review (e.g., motor outcomes for a Parkinson’s dementia population were not reported in this table). If primary outcomes were not identified by the authors, all noted outcomes relevant to the focus of this scoping review were listed. Prevention was listed as an outcome if the systematic review included an assessment of intervention impact on relative risk or disease incidence.
e Described interventions are only those relevant to this scoping review. Interventions for an excluded population and care- or caregiver-focused interventions are not listed.
NOTES: AD = Alzheimer’s disease; DLB = dementia with Lewy bodies; FTD = frontotemporal dementia; MCI = mild cognitive impairment; RCTs = randomized controlled trials.
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Ahn and Kim, 2023 | 2011–2020 | Persons age 60 years or older living with MCI | 22 | RCTs |
| Buele et al., 2023 | 1999–2022 | Healthy adults and persons living with MCI or dementia | 19 | RCTs; non-RCT clinical trials; pilot pretest-posttest; case study |
| Blackman et al., 2021* | 1993–2020 | Persons living with MCI or mild to moderate AD dementia | 16 | RCTs; crossover trials; prospective cohort studies |
| Cai et al., 2023 | 2010–2021 | Persons age 45 years or older living with MCI | 27 | RCTs |
| Corasaniti et al., 2024* | 2011–2023 | Persons living with dementia of any etiology | 10 | Clinical trials; retrospective studies |
| Castro et al., 2023** | 2010–2020 | Adults age 49 years or older at increased risk of dementia | 15 | RCTs |
| Chan et al., 2024 | 1994–2023 | Persons living with MCI or dementia | 35 | RCTs |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Cognition function |
Physical activity:
|
| Cognitive function | VR applications based on instrumental activities of daily living for cognitive training, rehabilitation, or stimulation |
| Neuropsychiatric and behavioral symptoms (sleep) |
Interventions to improve the duration or quality of sleep:
|
| Cognitive function | Mind–body exercise |
| Cognitive function; neuropsychiatric and behavioral symptoms |
Autophagy inducers:
|
| Cognitive function; reduced dementia risk factors | Multimodal lifestyle interventions that included diet and physical activity with or without cognitive training |
| Cognitive function | Computerized cognitive training |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Blackman et al., 2021* | 1993–2020 | Persons living with MCI or mild to moderate AD dementia | 16 | RCTs; crossover trials; prospective cohort studies |
| Cai et al., 2023 | 2010–2021 | Persons age 45 years or older living with MCI | 27 | RCTs |
| Corasaniti et al., 2024* | 2011–2023 | Persons living with dementia of any etiology | 10 | Clinical trials; retrospective studies |
| Castro et al., 2023** | 2010–2020 | Adults age 49 years or older at increased risk of dementia | 15 | RCTs |
| Chan et al., 2024 | 1994–2023 | Persons living with MCI or dementia | 35 | RCTs |
| Chen et al., 2022 | 2008–2021 | Persons living with MCI or mild to moderate AD | 16 | RCTs |
| Cho et al., 2023 | 2015–2021 | Persons living with dementia | 16 (14 not related to caregiving interventions) | RCTs |
| Connors et al., 2018 | 2002–2016 | Persons living with DLB | 21 (13 in DLB population not involving caregiving interventions) | RCTs; case studies; case series |
| Fu et al., 2022 | 2006–2021 | Cognitively normal adults | 36 | RCTs; prospective cohort studies |
| Gomez-Soria et al., 2023b | 2003–2021 | Adults over 65 years of age who are cognitively healthy or living with MCI or dementia | 30 | RCTs; nonrandomized controlled clinical trials; observational studies; pre-post studies |
| Gómez-Soria et al., 2023a | 2003–2021 | Adults age 65 years or older who are cognitively healthy or living with MCI or dementia | 33 | RCTs; nonrandomized controlled clinical trials; observational studies; pre-post studies |
| Guo et al., 2024 | 2005–2023 | Adults diagnosed with atrial fibrillation | 14 | RCTs; cohort studies; case-control studies |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Cognitive function | Transcranial direct current stimulation, alone or in combination with cognitive/memory training |
| Neuropsychiatric and behavioral symptoms |
Nonpharmacological interventions using information and communication technologies:
|
| Cognitive function; neuropsychiatric and behavioral symptoms; functional outcomes | Psychological interventions for visual hallucinations; physical exercise; gait cueing; music therapy; environmental modification for mirrored self-misidentification delusion; simulated presence; occupational therapy; electroconvulsive therapy; transcranial magnetic stimulation; transcranial direct current stimulation |
| Prevention of MCI, AD, and dementia; cognitive function | Mediterranean diet |
| Neuropsychiatric and behavioral symptoms; functional outcomes; quality of life | Cognitive stimulation, alone or in combination with acetylcholinesterase inhibitors |
| Cognitive function | Cognitive stimulation, alone or in combination with acetylcholinesterase inhibitors |
| Prevention of dementia; cognitive function | Rate-control and rhythm-control strategies, including atrial fibrillation ablation |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Hafdi et al., 2021** | 2010–2020 | Adults over 50 years of age without prior dementia diagnosis, including populations with known dementia risk factors and subjective cognitive symptoms or impairment | 9 | RCTs |
| Karamacoska et al., 2023 | 2012–2023 | Adults living with subjective cognitive decline, MCI, or vascular cognitive impairment | 12 | RCTs |
| Leow et al., 2023 | 2013–2021 | Adults age 60 years or older living with MCI | 10 | RCTs |
| Lin et al., 2022 | 1999–2021 | Persons living with AD | 67 | RCTs |
| López-Ortiz et al., 2023 | 2009–2021 | Adults at risk for or living with AD | 21 | RCTs; prospective studies; case–control studies |
| Miller et al., 2023 | 2012–2022 | Persons living with MCI or dementia related to AD | 16 (8 in relevant population) | RCTs |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Prevention of dementia and MCI; cognitive function |
Multimodal interventions targeting some combination of any of the following domains:
|
| Cognitive function |
Physical activity:
|
| Cognitive function; neuropsychiatric and behavioral symptoms | Mindfulness-based interventions (e.g., guided meditation, psychoeducation related to mindfulness) |
| Cognitive function |
Acupuncture treatments:
|
| Prevention of AD; cognitive function; functional outcomes; quality of life; neuropsychiatric and behavioral symptoms | Physical activity and exercise |
| Cognitive function | Repetitive transcranial magnetic stimulation targeting the dorsolateral prefrontal cortex |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Morrin et al., 2018 | 2003–2016 | Persons living with LBD | 15 (8 in relevant population) | Uncontrolled trials; case reports |
| Nimmons et al., 2024* | 1982–2023 | Persons living with dementia | 31 | RCTs |
| Papaioannou et al., 2022 | 1999–2021 | Persons living with MCI or dementia | 20 | RCTs |
| Profyri et al., 2022* | 1999–2021 | Persons living with severe dementia | 30 (23 not related to care or caregiver interventions) | RCTs |
| Ren et al., 2024 | 2012–2022 | Persons over 60 years of age living with MCI or dementia | 21 | RCTs |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Cognitive function; neuropsychiatric and behavioral symptoms; functional outcomes | Electroconvulsive therapy; repetitive transcranial magnetic stimulation; transcranial direct current stimulation; physical exercise; environmental intervention for “mirror sign” |
| Neuropsychiatric and behavioral symptoms |
Nonpharmacological interventions:
Pharmacological interventions:
|
| Cognitive function | Virtual reality applications used for cognitive training |
| Cognitive function; neuropsychiatric and behavioral symptoms; functional outcomes; mortality |
Nonpharmacological interventions:
Pharmacological interventions:
|
| Cognitive function | Virtual reality-based cognitive rehabilitation training |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Rostamzadeh et al., 2022 | 2007–2021 | Persons living with subjective cognitive decline and MCI who are at risk of AD dementia | 32 | RCTs; nonrandomized trials; case reports |
| Salzman et al., 2022** | 2011–2021 | Persons age 65 years or older living with MCI | 28 | RCTs |
| Shoesmith et al., 2023 | 2001–2021 | Persons living with dementia | 51 | RCTs; nonrandomized trials; cohort studies; pre-post studies; case studies; qualitative studies; mixed method study |
| Talar et al., 2022** | 2022–2021 | Adults age 60 years or older who are cognitively healthy or living with MCI or dementia | 74 | RCTs |
| Tosatti et al., 2022 | 2006–2018 | Adults living with AD | 4 | RCTs |
| Townsend et al., 2023 | 2006–2022 | Adults age 18 years or older | 93 | RCTs; prospective studies |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Cognitive function; neuropsychiatric and behavioral symptoms; quality of life | Psychotherapeutic and psychoeducational interventions, alone or in combination with other nonpharmacologic interventions (e.g., physical activity, cognitive training) |
| Cognitive function |
Multimodal interventions targeting some combination of any of the following domains:
|
| Neuropsychiatric and behavioral symptoms; quality of life | Animal-assisted interventions and robotic animal interventions |
| Cognitive function | Aerobic exercise and transcranial direct current stimulation, alone or in combination |
| Cognitive function; functional outcomes | Resveratrol supplementation |
| Cognitive function; prevention of MCI, AD, and dementia | Whole dietary patterns |
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Tulliani et al., 2022 | 2013–2022 | Persons age 60 years or older living with MCI or early-stage dementia | 13 | RCTs |
| van Middelaar et al., 2018* | 1996–2017 | Adults without prior dementia diagnosis | 9 | RCTs |
| Wang et al., 2023 | 2015–2023 | Persons living with MCI or AD | 17 | RCTs |
| Wang et al., 2022b | 1998–2019 | Adults who are cognitively healthy or living with MCI, AD, vascular dementia, or dementia with other causes | 95 | RCTs; cohort studies; cross-sectional studies |
| Watts et al., 2023* | Persons living with DLB | 135*** | RCTs; nonrandomized trials; open-label trials; longitudinal studies; case series; case reports | |
| Wei et al., 2023 | 1997–2021 | Participants with and without dementia | 48 | Cohort studies; prospective nested case-control studies |
| Wilfling et al., 2023 | 1999–2019 | Persons living with dementia | 19 (17 not related to care or caregiver interventions) | RCTs |
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Functional outcomes |
Cognitive remediation including the following alone or in combination:
|
| Prevention of all-cause dementia, AD, and vascular dementia |
Blood-pressure-lowering interventions:
|
| Cognitive function | Repetitive transcranial magnetic stimulation or transcranial direct current stimulation |
| Cognitive function; prevention of dementia | B vitamin supplementation |
| Cognitive function; neuropsychiatric and behavioral symptoms; mortality | Donepezil; rivastigmine; galantamine; memantine; modafinil/armodafinil; clozapine; quetiapine; risperidone; olanzapine; aripiprazole; dopamine antagonists; herbal medications (yokukasan, Feru-guard); ramelteon; clonazepam; antidepressants (citalopram, paroxetine) |
| Cognitive function; prevention of dementia, AD, or cognitive decline | Omega-3 fatty acids |
| Neuropsychiatric and behavioral symptoms (sleep) |
Nonpharmacologic interventions to improve sleep:
|
| Author, Year | Publication Dates of Studies Revieweda | Populationb | Total Studies Includedc | Included Study Designs |
|---|---|---|---|---|
| Xue et al., 2023** | 2013–2022 | Persons living with MCI or dementia | 29 | RCTs |
| Zeng et al., 2023 | 2011–2021 | Persons living with AD or a related dementia | 18 | RCTs |
| Zhan et al., 2021* | 2003–2020 | Persons living with vascular cognitive impairment | 23 | RCTs |
| Zhang et al., 2023 | 1995–2023 | Cognitively normal adults | 29 | Cohort studies |
*Indicates the inclusion of a systematic review that assessed both nonpharmacological and pharmacological interventions.
**Includes assessment of multimodal or multicomponent approaches.
***Indicates that the number of primary studies that were relevant to the focus of this scoping review could not be determined.
a Publication date range for primary articles included in listed systematic reviews is only inclusive of primary articles relevant to the focus of this scoping review (population, intervention types, outcomes of interest).
b Populations listed are only those relevant to the focus of this scoping review (e.g., if primary studies included in a systematic review were focused on Parkinson’s dementia, that population was not described in the table).
c When a systematic review included primary studies that were not a focus of this scoping review (e.g., wrong population, care- or caregiver-focused interventions), the number of relevant included studies for that systematic review is provided in parentheses.
| Primary Outcome Categories Assessedd | Relevant Interventions Assessede |
|---|---|
| Cognitive function; neuropsychiatric and behavioral symptoms; functional outcomes | Combined exercise (e.g., aerobic, strength) and cognitive interventions (e.g., cognitive training, cognitive stimulation) |
| Cognitive function |
Physical activity interventions:
|
| Cognitive function; functional outcomes | Gingko biloba extract alone or in combination with pharmacologic treatments (donepezil, nimodipine, huperzine, oxiracetam, piracetam, butylphthalide, ergoloid mesylate) |
| Prevention of AD | Physical activity |
d Reported outcomes are only those noted by the systematic review authors as primary outcomes and relevant to the focus of this scoping review (e.g., motor outcomes for a Parkinson’s dementia population were not reported in this table). If primary outcomes were not identified by the authors, all noted outcomes relevant to the focus of this scoping review were listed. Prevention was listed as an outcome if the systematic review included an assessment of intervention impact on relative risk or disease incidence.
e Described interventions are only those relevant to this scoping review. Interventions for an excluded population and care- or caregiver-focused interventions are not listed.
NOTES: AD = Alzheimer’s disease; DLB = dementia with Lewy bodies; FTD = frontotemporal dementia; LBD = Lewy body dementia; MCI = mild cognitive impairment; RCTs = randomized controlled trials.
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