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Affective and emotional dysregulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria
Open accessAbstract
BACKGROUND: Affective and emotional symptoms such as depression, anxiety, euphoria, and irritability are common neuropsychiatric symptoms (NPS) in pre-dementia and cognitively normal older adults. They comprise a domain of Mild Behavioral Impairment (MBI), which describes their emergence in later life as an at-risk state for cognitive decline and dementia, and as a potential manifestation of prodromal dementia. This selective scoping review explores the epidemiology and neurobiological links between affective and emotional symptoms, and incident cognitive decline, focusing on recent literature in this expanding field of research. METHODS: Existing literature in prodromal and dementia states was reviewed, focusing on epidemiology, and neurobiology. Search terms included: "mild cognitive impairment," "dementia," "prodromal dementia," "preclinical dementia," "Alzheimer's," "depression," "dysphoria," "mania," "euphoria," "bipolar disorder," and "irritability." RESULTS: Affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often being harbingers of neurodegenerative change and progressive cognitive decline. Nosological constraints in distinguishing between pre-existing psychiatric symptomatology and later life acquired NPS limit historical data utility, but emerging research emphasizes the importance of addressing time frames between symptom onset and cognitive decline, and age of symptom onset. CONCLUSION: Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies.
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“Cognitive decline encompasses mental health conditions like anxiety [45,46].”
From The Effect of Anxiety and Nutritional Habits on the Body Distortion of Athletes. (2025) · cites this paper as [45]
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“Experiential avoidance seeks to control the way or frequency of aversive private experiences [37] and has been associated with anxiety [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54].”
From The Effect of Anxiety and Nutritional Habits on the Body Distortion of Athletes. (2025) · cites this paper as [45]
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RetractedThe Effect of Anxiety and Nutritional Habits on the Body Distortion of Athletes.
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“In addition, data on the age of onset, or recency of BD diagnosis were not available; these are features that may be important in dementia risk assessments of neuropsychiatric syndromes (Ismail et al., 2016, Ismail et al., 2018; Matsuoka et al., 2019; Miao et al., 2022).”
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“…common in preclinical and prodromal dementia syndromes, often acting as a harbinger of neurodegenerative change and progressive cognitive decline (Ismail et al., 2018), late-life depression/anxiety is considered a risk factor for dementia and a prodrome for a subsequent neurodegenerative process…”
Chen, Z., Zhu, Z., Chen, D., Shi, Y., Zhao, J., Li, Y., Luo, Y., Li, H., & Lin, R. (2025) · Geriatric Nursing · doi:10.1016/j.gerinurse.2025.103575 · Cited by 1
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Ji, X., & Deng, S. (2025) · Population Health Management · doi:10.1177/19427891251395738 · Cited by 1
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Aravindhan, K., Mat, S., Xu, X. J., Hashim, N. N. A., Muraly, M. R., Saedon, N. I., Hasmukharay, K., Ahmad‐Annuar, A., Mahadzir, H., & Tan, M. P. (2025) · Scientific Reports · doi:10.1038/s41598-025-91650-4 · Cited by 1
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Ejiofor, T., Olajugba Oluwafunmilayo, J., Kala, A., Ephraim, A. D., & Okwoli, A. O. (2026) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000719 · Cited by 1
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“As sleep and affect are modifiable behavioral phe - nomena (McCrae et al., 2008), they are crucial targets for prevention (Ismail et al., 2018; Shi et al., 2018).”
Karp, J. F., Butters, M. A., Crivelli, L., Hermida, A. P., Gastiazoro, M. P., Gatchel, J. R., Gebara, M. A., Gentry, M. T., Mimura, M., Voshaar, R. C. O., et al. (2026) · International Psychogeriatrics · doi:10.1016/j.inpsyc.2026.100226 · Cited by 1
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“Cognitively unimpaired older adults with SCD are at increased risk for Alzheimer’s disease pathology and conversion to clinical states of mild cognitive impairment and dementia (Ismail et al., 2018; Kiselica, 2021; Vogel et al., 2017).”
Ling, Y., Wang, W., Jin, O., Wang, N., Wu, Y., Kong, X., Xu, L., Qi, Q., Wang, G., Yu, L., et al. (2024) · Food Reviews International · doi:10.1080/87559129.2024.2443069 · Cited by 2
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Callahan, B. L. (2020) · Canadian Psychology/Psychologie canadienne · doi:10.1037/cap0000204 · Cited by 1
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“…with a Studies examining the prevalence of individual MBI psychopathology domains have found that affective symptoms of emotional lability and anxiety, along with impulsivity, disinhibition, and irritability, are very common among cognitively healthy older adults and individuals with SCD [26, 27].”
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Metadata
- Authors
- Ismail, Z., Gatchel, J., Bateman, D. R., Barcelos-Ferreira, R., Cantillon, M., Jaeger, J., Donovan, N. J., Mortby, M. E., & Mortby, M. E.
- Affiliations
- University of Calgary (CA)
- Harvard University (US)
- Indiana University Indianapolis (US)
- Rutgers, The State University of New Jersey (US)
- Albert Einstein College of Medicine (US)
- Brigham and Women's Hospital (US)
- Australian National University (AU)
- Corresponding author
- Mortby, Moyra E.
- Mortby, Moyra Elizabeth
- ORCID
- Venue
- International Psychogeriatrics
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 30
- Issue
- 2
- Pages
- 185-196
- ISSN
- 1041-6102 (ISSN-L)
- PMC
- PMC7864664
- OpenAlex
- W2756173155
- Cited by
- 221
- References
- 115
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 26 · 2023: 34 · 2022: 23 · 2021: 26 · 2020: 35 · 2019: 17 · 2018: 13
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Update notices
- erratum (2019-01-01)
- Open access
- gold
- doi.org
- Licence
- Locations
- International Psychogeriatrics (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Funders
- Alzheimer's Association
- BrightFocus Foundation
- Consortium canadien en neurodégénérescence associée au vieillissement
- Rogers Family Foundation
- Alzheimer Society
- Canadian Institutes of Health Research
- Medical Research Council
- National Health and Medical Research Council (1102028)
- National Institute on Aging (K23AG058805)
- National Institute of Mental Health (R25MH094612)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- mild behavioral impairment, neuropsychiatric symptoms, prodromal dementia, depression, anxiety, irritability, euphoria, dysphoria, mania, bipolar disorder, mild cognitive impairment, cognitive decline, dementia prevention, neurodegeneration, older adults
- MeSH terms
- Affective Symptoms, Aged, Anxiety, Dementia, Depression, Emotions, Euphoria, Humans, Irritable Mood, Neuropsychological Tests, Cognitive Dysfunction, Symptom Assessment
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