The DOI matches its Crossref record; 115 of the 115 references it cites were found in a registry or an index.
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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Cites
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Cognitive reserve in ageing and Alzheimer's disease
Stern, Y. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70191-6 · Cited by 3,557 · cited 1×
“Finally, it has been proposed that chronic and recurrent anxiety disorders throughout the life-course may lead to avoidance behaviors, which in turn may result in lowered cognitive reserve as a result of less mental and social stimulation, therefore increasing the risk of dementia (Stern, 2012).”
BackgroundGlucocorticoids and Hippocampal Atrophy in Neuropsychiatric Disorders
Sapolsky, R. M. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.10.925 · Cited by 2,016 · cited 2×
“Further, cortisol-induced overstimulation of glucocorticoid receptors in the medial temporal lobe have also been linked to hippocampal atrophy (Sapolsky, 2000; Erickson et al., 2003), and stress has been postulated as a mechanism for hippocampal injury and volume loss (Sheline et al.”
Background'Vascular Depression' Hypothesis
Alexopoulos, G. S. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830220033006 · Cited by 1,843
Behavioral and psychological symptoms of dementia
Cerejeira, J., Lagarto, L., & Mukaetova-Ladinska, E. B. (2012) · Frontiers in Neurology · doi:10.3389/fneur.2012.00073 · Cited by 1,425 · cited 1×
“…emotional dysregulation symptoms are among the most common NPS presenting in mild cognitive impairment (MCI) (Peters et al., 2012), and are, along with other NPS, associated with poorer outcomes overall (Cerejeira et al., 2012) and higher conversion rates from MCI to dementia (Palmer et al., 2007).”
BackgroundSheline, Y. I., Sanghavi, M., Mintun, M. A., & Gado, M. H. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-12-05034.1999 · Cited by 1,382
Cytokine-Associated Emotional and Cognitive Disturbances in Humans
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Ismail, Z., Smith, E. E., Geda, Y., Sultzer, D., Brodaty, H., Smith, G., Agüera‐Ortiz, L., Sweet, R., Miller, D., Lyketsos, C. G., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.05.017 · Cited by 818
MRI-defined vascular depression
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“The robust relationship between cerebrovascular disease and depressive symptoms may underlie this association (Alexopoulos et al., 1997; Krishnan et al., 1997).”
BackgroundKrauthammer, C. (1978) · Archives of General Psychiatry · doi:10.1001/archpsyc.1978.01770350059005 · Cited by 652 · cited 3×
“…an etiology other than bipolar disorder, causes the majority of new onset mania in older adults (Krauthammer and Klerman, 1978; Brooks and Hoblyn, 2005), which include neurodegenerative disorders, such as predementia syndromes and dementias (Krauthammer and Klerman, 1978; Brooks and Hoblyn, 2005).”
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Mild Behavioral Impairment as a Marker of Cognitive Decline in Cognitively Normal Older Adults
Creese, B., Brooker, H. J., Ismail, Z., Wesnes, K. A., Hampshire, A., Khan, Z., Megalogeni, M., Corbett, A., Aarsland, D., & Ballard, C. G. (2019) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2019.01.215 · Cited by 197
“dysregulation (mood and anxiety symptoms) (7); impulse dyscontrol/agitation/abnormal reward salience (changes in response inhibition and self-regulation); social inappropriateness (impaired social cognition) (8); and abnormal thoughts/perception (psychosis) (9), assessed individually and collectively for their”
BackgroundWise, E. A., Rosenberg, P. B., Lyketsos, C. G., & Leoutsakos, J. (2019) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2019.02.006 · Cited by 187
“Moreover, studying these individuals may help us identify the causal pathway between anxiety, depression, and other affective symptoms and cognitive impairment [34].”
BackgroundMild Behavioral Impairment and Subjective Cognitive Decline Predict Cognitive and Functional Decline
Ismail, Z., McGirr, A., Gill, S., Hu, S., Forkert, N. D., & Smith, E. E. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201184 · Cited by 175
Mallo, S. C., Ismail, Z., Pereiro, A. X., Facal-Mayo, D., Lojo‐Seoane, C., Campos‐Magdaleno, M., & Juncos‐Rabadán, O. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180131 · Cited by 155
“In the ISTAART-AA MBI criteria, symptoms are divided into the following domains: decreased motivation [46, 47], affective dysregulation [48, 49], impulse dyscontrol [4, 50], social inappropriateness [51, 52], and abnormal though or perception [53, 54].”
Magierski, R., Sobów, T., Schwertner, E., & Religa, D. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01168 · Cited by 129
“cognitive decline and dementia, biomarker of cognitive decline, or even a potential manifestation of prodromal dementia (Ismail et al., 2018; Taragano et al., 2018; Creese et al., 2019).”
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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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