Open research questions in Dementia and Cognitive Impairment Research

What the literature leaves open

• Full publication of long-term extension analyses, including comparisons between early-and delayed-treatment groups, to clarify the durability and cumulative clinical impact of treatment effects - Greater attention to biological target engagement, trial design and therapeutic generation would provide a more clinically informative synthesis of the available evidence

  Interpreting evolving evidence in Alzheimer’s disease: implications for dementia clinicians · 2026 · DOI

• The absence of meaningful stratification by developmental phase, mechanism or trial design introduces a substantial interpretive limitation. The review's methodology may obscure clinically relevant effects that have met contemporary regulatory standards.

  Interpreting evolving evidence in Alzheimer’s disease: implications for dementia clinicians · 2026 · DOI

• Identifying and characterizing different caregiving network types for each racial and ethnic group. Assessing the associations between caregiving network characteristics and unmet care needs. Addressing within-group variation in caregiving networks to inform equitable, culturally responsive caregiving policies.

  Racial and Ethnic Differences in Caregiving Networks and Unmet Care Needs Among People Living With Cognitive Impairment · 2026 · DOI

• Other groups were excluded from the analysis due to the small sample size (N=241), - The sample was restricted to community-dwelling adults, - The analysis was limited to the 2023 wave of NHATS

  Racial and Ethnic Differences in Caregiving Networks and Unmet Care Needs Among People Living With Cognitive Impairment · 2026 · DOI

• Assessing daily fluctuations in control and cognition can be challenging due to the need for frequent and repeated measurements. Capturing the dynamic, within-person relationship between perceived control and cognition in daily life requires innovative methodological approaches. The study had to handle missing data using FIML.

  Coupled Changes in Daily Control Beliefs and Cognition: Variations by Education and Income · 2026 · DOI

• Examine the relationship between perceived control and other cognitive functions - Investigate the mechanisms underlying the relationship between perceived control and episodic memory - Extend the study to other socioeconomic populations

  Coupled Changes in Daily Control Beliefs and Cognition: Variations by Education and Income · 2026 · DOI

• Participants' limited access to information about dementia screening. Symptom-oriented healthcare-seeking behavior among older adults. Economic concerns and perceived value of dementia screening.

  Dilemmas of early dementia screening among community-dwelling older adults: a qualitative study from the perspective of social determinants of health · 2026 · DOI

• Small sample size of 23 participants, - Limited to community-dwelling older adults in Wuhan, China, - No apparent severe cognitive impairment was an inclusion criterion

  Dilemmas of early dementia screening among community-dwelling older adults: a qualitative study from the perspective of social determinants of health · 2026 · DOI

• The growing prevalence of MCI has generated considerable scientific interest in identifying modifiable factors that may influence cognitive trajectories during aging.

  Associations of Social Support, Loneliness, and Physical Activity with Cognitive Function in Older Adults with Mild Cognitive Impairment · 2026 · DOI

• Investigate the underlying mechanisms of the relationship between depressive symptoms and cognitive decline in detail. Examine the relationship between depressive symptoms and cognitive decline in different populations. Explore the potential of plasma biomarkers for screening and diagnosing dementia. Investigate the effects of interventions targeting depressive symptoms on cognitive decline

  Plasma phosphorylated tau 217 and neurofilament light chain on the association between depressive symptoms and cognitive decline: The Shanghai Aging Study · 2026 · DOI

• The underlying mechanism that links depressive symptoms and cognitive decline is still uncertain. Plasma biomarkers offer an opportunity for a cost-and time-effective approach to screening and diagnosing dementia.

  Plasma phosphorylated tau 217 and neurofilament light chain on the association between depressive symptoms and cognitive decline: The Shanghai Aging Study · 2026 · DOI

• The study was a secondary analysis of cross-sectional baseline data, - The sample size was limited to 88 individuals with suspected MCI, - The study did not improve over a null model incorporating global cognitive function only (p = 0.348)

  Subjective estimation of cognitive function in mild cognitive impairment: relationship with neurodegenerative and non-degenerative factors · 2026 · DOI

• Further research is needed to examine the relationship between metacognitive error and progression to dementia, - Longitudinal studies are required to confirm the findings, - Research should investigate the underlying mechanisms of metacognitive error in MCI

  Subjective estimation of cognitive function in mild cognitive impairment: relationship with neurodegenerative and non-degenerative factors · 2026 · DOI

• the study did not fully confirm temporal directionality, - the association between psychosis and NFL disappeared after FDR correction, - the study had a limited sample size, - the study did not investigate the underlying mechanisms of NPSs

  Plasma neurofilament light chain and regional brain atrophy mediate the association of neuropsychiatric symptoms with cognition in Alzheimer’s disease: evidence from two population-based studies · 2026 · DOI

• investigate the underlying mechanisms of NPSs, - examine the longitudinal relationships of NPSs with incident cognitive decline, - evaluate the cognitive discrimination of NPSs and NFL, - examine the onset hazards of NPS subsyndromes

  Plasma neurofilament light chain and regional brain atrophy mediate the association of neuropsychiatric symptoms with cognition in Alzheimer’s disease: evidence from two population-based studies · 2026 · DOI

• confounding by indication, - reverse causation, - limited to UK Biobank participants, - no curative treatments available for dementia

  Antidepressant use and dementia, cognitive measures, and neuroimaging outcomes: A population-based cohort study · 2026 · DOI

• investigating the association between antidepressant use and dementia in different populations, - examining the effects of antidepressant use on cognitive decline and neurodegeneration, - developing scalable prevention strategies for dementia

  Antidepressant use and dementia, cognitive measures, and neuroimaging outcomes: A population-based cohort study · 2026 · DOI

• The lack of allocation concealment and incomplete blinding in most studies. The methodological quality scores of the included studies ranged from 4 to 7, with a mean score of 6.0, indicating an acceptable overall quality but with some limitations.

  Effects of multicomponent exercise on global cognitive function, executive function, and brain-derived neurotrophic factors in older adults with mild cognitive impairment: a systematic review and three-level meta-analysis · 2026 · DOI

• Further studies are needed to confirm the findings and to explore the effects of multicomponent exercise on global cognitive function and BDNF levels. Research on the optimal duration and frequency of multicomponent exercise for improving cognitive function in older adults with MCI is needed.

  Effects of multicomponent exercise on global cognitive function, executive function, and brain-derived neurotrophic factors in older adults with mild cognitive impairment: a systematic review and three-level meta-analysis · 2026 · DOI

• A large volume of retrieved studies may complicate data charting and limit subgroup comparisons. Inconsistent or incomplete reporting of living arrangement and supporter availability may limit the development of a preliminary descriptive framework. The review may be limited by the quality and availability of existing research on help-seeking for dementia diagnosis.

  Exploring representation of people without cohabiting carers in research on help-seeking for dementia diagnosis: a scoping review protocol · 2026 · DOI

• inform recommendations for more consistent inclusion and reporting of these variables in future research, - development of more inclusive approaches to dementia diagnosis research

  Exploring representation of people without cohabiting carers in research on help-seeking for dementia diagnosis: a scoping review protocol · 2026 · DOI

• Future research could explore how specific interventions affect resilience and cognitive reserve across different species. Investigating the role of environmental enrichment on stress responses in both animals and humans could provide further insights into resilience mechanisms.

  Cognitive reserve and adaptive resilience: a conceptual analysis of a cross-species framework for neuropsychology and cognitive aging · 2026 · DOI

• The gap identified is the need to understand how reserve-related capacities are developed and expressed across different species. There is a lack of integration between research on adaptive resilience and cognitive reserve models.

  Cognitive reserve and adaptive resilience: a conceptual analysis of a cross-species framework for neuropsychology and cognitive aging · 2026 · DOI

• Further research is needed to develop and test measures to label LEs with precision and coherence - Research should consider the challenges and complexity of capturing LEs and developing definitional criteria - Studies should explore the epidemiology of LEs, including their possible catalysts or neurological pathways

  Lucid episodes in people with advanced dementia: characterizing caregiver reports to advance definition and measurement of episodes · 2025 · DOI

• There is no scientific consensus on a precise definition of lucid episodes. Current models of Alzheimer's disease and related dementias assume lost cognitive capacity is irretrievable, but lucid episodes challenge this assumption. Prior work has not fully characterized the heterogeneous nature of lucid episodes.

  Lucid episodes in people with advanced dementia: characterizing caregiver reports to advance definition and measurement of episodes · 2025 · DOI

Most-cited papers in Dementia and Cognitive Impairment Research

• The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment · Journal of the American Geriatrics Society · 2005 · 22,342 citations
• Dementia prevention, intervention, and care: 2020 report of the Lancet Commission · The Lancet · 2020 · 9,004 citations
• A New Clinical Scale for the Staging of Dementia · The British Journal of Psychiatry · 1982 · 5,523 citations
• Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease · JAMA · 1997 · 4,791 citations
• Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019 · The Lancet Public Health · 2022 · 4,603 citations
• A Short Portable Mental Status Questionnaire for the Assessment of Organic Brain Deficit in Elderly Patients† · Journal of the American Geriatrics Society · 1975 · 4,341 citations
• The Mini‐Mental State Examination: A Comprehensive Review · Journal of the American Geriatrics Society · 1992 · 4,080 citations
• Global prevalence of dementia: a Delphi consensus study · The Lancet · 2005 · 3,859 citations
• The Global Deterioration Scale for assessment of primary degenerative dementia · American Journal of Psychiatry · 1982 · 3,794 citations
• Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease · New England Journal of Medicine · 2012 · 3,361 citations

Most recent work

• Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials · The Lancet · 2026
• Predicting onset of symptomatic Alzheimerʼs disease with plasma p-tau217 clocks · Nature Medicine · 2026
• Cognability across adulthood: A qualitative investigation of neighborhoods and cognitive health behaviors · Social Science & Medicine · 2026
• A dual-model AI framework for Alzheimer’s disease diagnosis using clinical and MRI data · Frontiers in Medicine · 2026
• Alzheimer's disease neuropathology plasma biomarkers and cognition in midlife: a community-based cohort study · The Lancet · 2026
• An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration · Nature Medicine · 2026
• Lifestyle-associated blood metabolic pathways and functional performance in cognitive aging · Scientific Reports · 2026
• Population attributable fractions of a wide range of peripheral diseases for the burden of dementia · Nature Human Behaviour · 2026
• Experience of living with mild cognitive impairment: A meta-synthesis and conceptual integration of dynamic cognitive, psychological, and social dimensions · International Journal of Nursing Studies · 2026
• The blood metabolome of brain health in midlife and influences of genes, microbiome and exposome · Nature Aging · 2026

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