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.
“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]
The Anxiety section links anxiety symptoms to poorer cognitive function and cognitive decline, and describes anxiety among neuropsychiatric symptoms in people with cognitive decline. It does not say that cognitive decline itself encompasses mental health conditions; it treats anxiety as an associated symptom or possible risk marker. No page number was available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredExperiential avoidance has been associated with anxiety.
“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]
The Anxiety section discusses a proposed link from chronic anxiety disorders to avoidance behaviors, but it does not identify those behaviors as experiential avoidance or report an association between experiential avoidance and anxiety. Searches for “experiential avoidance” and avoidance of aversive private experiences found no passage addressing that specific claim; page numbers were unavailable in our copy. (LLM, conf=0.74)
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“The pathophysiology of late onset bipolar disorder is thought to be different from early onset bipolar disorder with the late onset group having higher rates of neurologic and vascular brain abnormalities (Young and Klerman, 1992; Tohen et al., 1994; Fujikawa et al., 1995; Sami et al., 2015).”
BackgroundPomara, N., Bruno, D., Sarreal, A. S., Hernando, R. T., Nierenberg, J. J., Petkova, E., Sidtis, J. J., Wısnıewskı, T., Mehta, P. D., Praticò, D., et al. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11081153 · Cited by 142 · see citing works
Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels
Babulal, G. M., Ghoshal, N., Head, D. M., Vernon, E. K., Holtzman, D. M., Benzinger, T. L. S., Fagan, A. M., Morris, J. C., & Roe, C. M. (2016) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2016.04.004 · Cited by 142 · see citing works
Stone, K. (1989) · The British Journal of Psychiatry · doi:10.1192/bjp.155.2.220 · Cited by 138 · see citing works
Does Anxiety Affect Risk of Dementia? Findings From the Caerphilly Prospective Study
Gallacher, J., Bayer, A., Fish, M., Pickering, J., Pedro, S., Dunstan, F., Ebrahim, S., & Ben-Shlomo, Y. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181a6177c · Cited by 137 · see citing works
Mania in the Elderly: A 5–7 Year Follow‐Up
Dhingra, U., & Rabins, P. V. (1991) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1991.tb03597.x · Cited by 133 · cited 1× · see citing works
“There have also been case reports of bipolar disorder mimicking BvFTD, with failure to progress to “probable” BvFTD after 3–7 years of observation (Dols et al., 2016).”
BackgroundGerritsen, L., Comijs, H. C., van der Graaf, Y., Knoops, A. J. G., Penninx, B. W. J. H., & Geerlings, M. I. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.029 · Cited by 132 · cited 3× · see citing works
“proteinopathies and/or cerebrovascular lesions) (Ballmaier et al., 2008; Gerritsen et al., 2011; Pomara et al., 2012; Donovan et al., 2015; Babulal et al., 2016; Krell-Roesch et al., 2016).”
BackgroundInfluentialGatchel, J. R., Donovan, N. J., Locascio, J. J., Schultz, A. P., Becker, J. A., Chhatwal, J. P., Papp, K. V., Amariglio, R. E., Rentz, D. M., Blacker, D., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170001 · Cited by 125 · see citing works
Pietrzak, R. H., Maruff, P. T., Woodward, M., Fredrickson, J., Fredrickson, A., Krystal, J. H., Southwick, S. M., & Darby, D. (2011) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3182107e24 · Cited by 118 · see citing works
Depressive Symptoms and Biomarkers of Alzheimer’s Disease in Cognitively Normal Older Adults
Donovan, N. J., Hsu, D. C., Dagley, A. S., Schultz, A. P., Amariglio, R. E., Mormino, E. C., Okereke, O. I., Rentz, D. M., Johnson, K. A., Sperling, R. A., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142940 · Cited by 115 · see citing works
Prospective Study of Anxiety and Incident Stroke
Lambiase, M. J., Kubzansky, L. D., & Thurston, R. C. (2013) · Stroke · doi:10.1161/strokeaha.113.003741 · Cited by 114 · see citing works
Depressive symptoms, clinical AD, and cortical plaques and tangles in older persons
Wilson, R. S., Schneider, J. A., Bienias, J. L., Arnold, S. E., Evans, D. A., & Bennett, D. A. (2003) · Neurology · doi:10.1212/01.wnl.0000092914.04345.97 · Cited by 109 · cited 3× · see citing works
“, 2016) have not shown robust relationships between depressive symptoms and amyloid plaques or neurofibrillary tangles (Wilson et al., 2003; Wilson et al., 2014; McCutcheon et al., 2016).”
BackgroundResultInfluentialHermida, A. P., McDonald, W. M., Steenland, K., & Levey, A. I. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.127 · Cited by 100 · cited 4× · see citing works
“Depressive symptoms may be more common in vascular dementia than in AD dementia (O’Brien, 2003), and depression has been associated with amnestic (Steenland et al., 2012; Geda et al., 2014) as well as both amnestic and non-amnestic MCI (Hermida et al., 2012).”
BackgroundInfluentialPatterns of Neuropsychiatric Symptoms in MCI and Risk of Dementia
Forrester, S. N., Gallo, J., Smith, G. S., & Leoutsakos, J. (2015) · The American journal of geriatric psychiatry · doi:10.1016/j.jagp.2015.05.007 · Cited by 95 · cited 8× · see citing works
“Clinicopathological correlates of depression in early Alzheimer’s disease in the NACC.”
BackgroundInfluentialLobo, A., López‐Antón, R., De‐la‐Cámara, C., Quintanilla, M. Á., Campayo, A., Saz, P., & Workgroup, Z. (2008) · Neurotoxicity Research · doi:10.1007/bf03033815 · Cited by 90 · cited 1× · see citing works
“…has now been shown that irritability is among the neurobehavioral symptoms which portends more rapid decline in several datasets including NACC (Leoutsakos et al., 2015; Forrester et al., 2016); the Spanish ZARADEMP cohort (Lobo et al., 2008) and the Mayo Clinic Study of aging (Geda et al., 2014).”
BackgroundRisk Factors for Behavioral Abnormalities in Mild Cognitive Impairment and Mild Alzheimer's Disease
Apostolova, L. G., Di, L. J., Duffy, E. L., Brook, J. K., Elashoff, D. A., Tseng, C., Fairbanks, L. A., & Cummings, J. L. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000351009 · Cited by 87 · see citing works
Risk of dementia and death in community-dwelling older men with bipolar disorder
Almeida, O. P., McCaul, K. A., Hankey, G. J., Yeap, B. B., Golledge, J., & Flicker, L. A. (2016) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.115.180059 · Cited by 81 · cited 5× · see citing works
“Subgroups, who developed bipolar disorder over the age of 70 or within the past five years had the greatest risk for development of dementia (Almeida et al., 2016), very similar to the evidence for depressive symptoms (Almeida et al., 2017).”
BackgroundResultInfluentialDepression, anxiety, and the cardiovascular system: the cardiologist's perspective.
Sheps, D. S., & Sheffield, D. (2001) · PubMed · Cited by 80 · see citing works
De Winter, F.-L., Emsell, L., Bouckaert, F., Claes, L., Jain, S., Farrar, G., Billiet, T., Evers, S., Van den Stock, J., Sienaert, P., et al. (2017) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.16030319 · Cited by 80 · see citing works
Tighe, S. K., Oishi, K., Mori, S., Smith, G. S., Albert, M., Lyketsos, C. G., & Mielke, M. M. (2012) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/appi.neuropsych.11120375 · Cited by 77 · see citing works
Prevalence of Neuropsychiatric Symptoms in CIND and Its Subtypes: The Cache County Study
Peters, M. E., Rosenberg, P. B., Steinberg, M., Tschanz, J. T., Norton, M. C., Welsh-Bohmer, K. A., Hayden, K. M., Breitner, J. C. S., & Lyketsos, C. G. (2011) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e318211057d · Cited by 75 · see citing works
The impact of anxiety on conversion from mild cognitive impairment to Alzheimer's disease
Devier, D. J., Pelton, G. H., Tabert, M. H., Liu, X., Cuasay, K., Eisenstadt, R., Marder, K. S., Stern, Y., & Devanand, D. P. (2009) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2263 · Cited by 75 · cited 1× · see citing works
“%) older adults with mania went on to develop cognitive impairment within 5–7 years (Dhingra and Rabins, 1991).”
BackgroundNeuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease
Ng, K. P., Pascoal, T. A., Mathotaarachchi, S. S., Chung, C.-O., Benedet, A. L., Shin, M., Kang, M. S., Li, X., Ba, M., Kandiah, N., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000003916 · Cited by 75 · see citing works
Mortby, M. E., Burns, R. A., Eramudugolla, R., Ismail, Z., & Anstey, K. J. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170050 · Cited by 72 · cited 2× · see citing works
“Evidence links NPS in advance of dementia to a greater likelihood of cognitive impairment (Mortby et al., 2017) and cognitive decline (Geda et al.”
BackgroundPredictors of progression to severe Alzheimer's disease in an incidence sample
Rabins, P. V., Schwartz, S., Black, B. S., Corcoran, C. D., Fauth, E. B., Mielke, M. M., Christensen, J., Lyketsos, C. G., & Tschanz, J. T. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.01.003 · Cited by 70 · see citing works
Li, X., & Li, Z. (2017) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4694 · Cited by 69 · cited 1× · see citing works
“Nonetheless, a recent meta-analysis by Li and Li (2017) of 11 studies showed a pooled hazard ratio of conversion to dementia for co-morbid anxiety and MCI compared to those without anxiety (hazard ratio (HR): 1.18, 95% CI: 1.07–1.31, p = 0.002).”
BackgroundInfluentialCerami, C., Marcone, A., Galimberti, D., Villa, C., Scarpini, E. A., & Cappa, S. F. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110788 · Cited by 64 · cited 1× · see citing works
“…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).”
BackgroundLópez‐Antón, R., Santabárbara, J., De‐la‐Cámara, C., Gracia‐García, P., Lobo, E., Marcos, G., Pírez, G., Saz, P., Haro, J. M., Rodríguez‐Mañas, L., et al. (2014) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12297 · Cited by 64 · see citing works
Late onset mania as an organic syndrome: A review of case reports in the literature
Sami, M., Khan, H., & Nilforooshan, R. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.08.027 · Cited by 64 · cited 1× · see citing works
“The pathophysiology of late onset bipolar disorder is thought to be different from early onset bipolar disorder with the late onset group having higher rates of neurologic and vascular brain abnormalities (Young and Klerman, 1992; Tohen et al., 1994; Fujikawa et al., 1995; Sami et al., 2015).”
BackgroundManic‐like state after bilateral orbitofrontal and right temporoparietal injury
Bakchine, S., Lacomblez, L., Benoit, N. B., Parisot, D., Chain, F., & Lhermitte, F. (1989) · Neurology · doi:10.1212/wnl.39.6.777 · Cited by 63 · cited 2× · see citing works
“Lesions in a number of different brain regions have been associated with the development of secondary mania, including bilateral orbitofrontal, right temporoparietal, right basal and medial temporal lobe, basal ganglia, thalamic and right frontotemporal (Bakchine et al., 1989; Danel et al., 1989; Turecki et al., 1993;…”
BackgroundWeissberger, G. H., Melrose, R. J., Narvaez, T. A., Harwood, D. G., Mandelkern, M. A., & Sultzer, D. L. (2017) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2017.01.017 · Cited by 63 · see citing works
Tapiainen, V., Hartikainen, S. A., Taipale, H. T., Tiihonen, J., & Tolppanen, A. (2017) · European Psychiatry · doi:10.1016/j.eurpsy.2017.02.486 · Cited by 62 · cited 6× · see citing works
“…and case-control epidemiological studies has highlighted the need for a determination of the age of onset of symptoms and of the timewindow between onset of symptoms and decline in cognition to properly ascertain risk (Almeida et al., 2017; Singh-Manoux et al., 2017; Tapiainen et al., 2017).”
BackgroundInfluentialLatent classes of neuropsychiatric symptoms in NACC controls and conversion to MCI or dementia
Leoutsakos, J., Forrester, S. N., Lyketsos, C., & Smith, G. S. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150421 · Cited by 60 · cited 9× · see citing works
“Clinicopathological correlates of depression in early Alzheimer’s disease in the NACC.”
BackgroundResultInfluentialde Sousa, M. F. B., Santos, R. L., Garriga, O. T., Dias, R., Dourado, M. C. N., & Conde‐Sala, J. L. (2016) · International Psychogeriatrics · doi:10.1017/s1041610216000508 · Cited by 51 · cited 1× · see citing works
“Irritability is common among neurobehavioral symptoms in neurodegenerative disease and causes increased burden on patients, caregivers, and the community alike (Sousa et al., 2016).”
BackgroundBurke, S. L., Maramaldi, P., Cadet, T. J., & Kukull, W. A. (2016) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2016.04.006 · Cited by 49 · see citing works
Anxiety and regional cortical glucose metabolism in patients with Alzheimer's disease.
Hashimoto, H., Monserratt, L., Nguyen, P., Feil, D., Harwood, D., Mandelkern, M., & Sultzer, D. (2006) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/jnp.2006.18.4.521 · Cited by 47 · see citing works
Krell‐Roesch, J., Ruider, H., Lowe, V. J., Stokin, G. B., Pink, A., Roberts, R. O., Mielke, M. M., Knopman, D. S., Christianson, T. J. H., Machulda, M. M., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160326 · Cited by 45 · see citing works
Floris, G., Borghero, G., Cannas, A., Stefano, F. D., Murru, M. R., Corongiu, D., Cuccu, S., Tranquilli, S., Marrosu, M. G., Chiò, A., et al. (2013) · Journal of Neurology · doi:10.1007/s00415-013-6833-2 · Cited by 41 · see citing works
Psychiatric Phenomena in Dementia of the Alzheimer Type
Burns, A. S. (1992) · International Psychogeriatrics · doi:10.1017/s1041610292001145 · Cited by 40 · cited 1× · see citing works
“BDNF signaling is necessary for antidepressant response, and BDNF deletion attenuates this response (Castrén and Kojima, 2017).”
BackgroundTing, C., Rajji, T. K., Ismail, Z., Tang‐Wai, D. F., Apanasiewicz, N., Miranda, D., Mamo, D. C., & Mulsant, B. H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010151 · Cited by 38 · see citing works
Lyketsos, C. G., Corazzini, K., & Steele, C. (1995) · Journal of Neuropsychiatry · doi:10.1176/jnp.7.3.350 · Cited by 36 · cited 1× · see citing works
“However, symptoms of elation, euphoria, and mania are relatively rare in AD type dementia as compared to FTD, with an estimated prevalence of 2.2–3.5% (Burns, 1992; Lyketsos et al., 1995).”
BackgroundInfluentialBehavioral Symptoms in Vascular Cognitive Impairment and Vascular Dementia
O'Brien, J. T. (2003) · International Psychogeriatrics · doi:10.1017/s1041610203009098 · Cited by 36 · cited 2× · see citing works
“Depressive symptoms may be more common in vascular dementia than in AD dementia (O’Brien, 2003), and depression has been associated with amnestic (Steenland et al., 2012; Geda et al., 2014) as well as both amnestic and non-amnestic MCI (Hermida et al., 2012).”
BackgroundDepression Versus Dementia: Is This Construct Still relevant?
Ismail, Z., Malick, A., Smith, E. E., Schweizer, T. A., & Fischer, C. E. (2014) · Neurodegenerative Disease Management · doi:10.2217/nmt.14.5 · Cited by 36 · cited 2× · see citing works
“, 2013) and may constitute a prodrome (Ismail et al., 2014).”
BackgroundLate life bipolar disorder evolving into frontotemporal dementia mimic
Dols, A., Krudop, W. A., Moeller, C., Shulman, K. I., Sajatovic, M., & Pijnenburg, Y. A. L. (2016) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s99229 · Cited by 36 · see citing works
Gonzales, M. M., Insel, P. S., Nelson, C. J., Tosun, D., Mattsson, N., Mueller, S. G., Sacuiu, S. F., Bickford, D. D., Weiner, M. W., & Mackin, R. S. (2017) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2017.04.011 · Cited by 34 · see citing works
Cortisol and Self-report Measures of Anxiety as Predictors of Neuropsychological Performance
Leininger, S. L., & Skeel, R. (2012) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acs035 · Cited by 33 · cited 1× · see citing works
“Cortisol levels are in turn related to symptom severity and poorer outcomes on neuropsychological tests (Erickson et al., 2003; Leininger and Skeel, 2012; Mantella et al. 2008; Rosnick et al., 2013).”
BackgroundDepression and the risk of vascular dementia: a population‐based retrospective cohort study
Lin, W., Hu, L., Tsai, S., Yang, A. C., & Shen, C. (2016) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4493 · Cited by 32 · cited 1× · see citing works
“In addition to AD, converging evidence supports depression as a risk factor and/or prodrome for vascular dementia (Barnes et al., 2012; Lin et al., 2017).”
BackgroundTascone, L. D. S., & Bottino, C. M. D. C. (2013) · Dementia & Neuropsychologia · doi:10.1590/s1980-57642013dn70300002 · Cited by 30 · cited 2× · see citing works
“Disinhibition together with emotional lability in dementia has been associated with orbitofrontalsubcortical circuit dysfunction (Tascone and Bottino, 2013).”
BackgroundMood Disorders Secondary to Stroke.
Robinson, R. (1997) · PubMed · doi:10.1053/scnp00200244 · Cited by 29 · see citing works
Clinicopathological correlates of depression in early Alzheimer's disease in the NACC
McCutcheon, S. T., Han, D., Troncoso, J., Koliatsos, V. E., Albert, M., Lyketsos, C. G., & Leoutsakos, J. S. (2016) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4435 · Cited by 29 · see citing works
Bipolar disorder following a left basal-ganglia stroke
Turecki, G., Mari, J. D. J., & Porto, J. A. D. (1993) · The British Journal of Psychiatry · doi:10.1192/bjp.163.5.690 · Cited by 28 · cited 2× · see citing works
“Lesions in a number of different brain regions have been associated with the development of secondary mania, including bilateral orbitofrontal, right temporoparietal, right basal and medial temporal lobe, basal ganglia, thalamic and right frontotemporal (Bakchine et al., 1989; Danel et al., 1989; Turecki et al., 1993;…”
BackgroundRosnick, C. B., Rawson, K. S., Butters, M. A., & Lenze, E. J. (2013) · Aging & Mental Health · doi:10.1080/13607863.2012.761673 · Cited by 23 · cited 1× · see citing works
“Cortisol levels are in turn related to symptom severity and poorer outcomes on neuropsychological tests (Erickson et al., 2003; Leininger and Skeel, 2012; Mantella et al. 2008; Rosnick et al., 2013).”
BackgroundSchölzel-Dorenbos, C. J. M. (2006) · Tijdschrift voor VerpleeghuisGeneeskunde · doi:10.1007/bf03075177 · Cited by 14 · cited 1× · see citing works
“While the early presentation of NPS in the course of neurodegenerative disease has traditionally raised suspicion of behavioral variant frontotemporal dementia (bvFTD), evidence also suggests that NPS can emerge in advance of any dementia syndrome (Taragano et al., 2009).”
BackgroundCholinesterase-inhibitor Associated Mania: A Case Report and Literature Review
Jalal, H., Ganesh, A., Lau, R. W. M., Lysack, J. T., & Ismail, Z. (2014) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100016735 · Cited by 13 · cited 2× · see citing works
“…nosology with insufficient attention given to their late life onset and consequently their frequent misclassification as idiopathic psychiatric illness (Woolley et al., 2011), potentially exposing patients to inappropriate medications or delays in dementia diagnosis (Jalal et al., 2014).”
Background[Mood disorders and right hemisphere infarction].
Danel, T., Comayras, S., Goudemand, M., Leys, D., Destée, A., Lauth, B., & Dupard, T. (1989) · PubMed · Cited by 7 · see citing works
[White matter hyperintensities and cognitive function in patients with late onset mania].
Ramírez‐Bermúdez, J., Carrillo‐Mezo, R., Atriano, C., Sánchez, D., Marrufo, O., Berlanga, C., Guadamuz, A., Taboada, J., & Rı́os, C. (2016) · PubMed · Cited by 4 · see citing works
New Insights Into Brain Mechanisms Underlying Neuropsychiatric Symptoms in Alzheimer Disease
Rosenberg, P. B. (2017) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2017.02.023 · Cited by 2 · cited 1× · see citing works
“…to agitation (right temporal, right frontal, bilateral middle, and posterior cingulate gyri) but differed in specific regions (right insular, precentral, and postcentral gyri) (Weissberger et al., 2017), reflecting neurodegeneration in regions associated with core AD pathology (Rosenberg, 2017).”
Background
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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 · see citing works
“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 179 · see citing works
“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 169 · see citing works
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 · see citing works
“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 121 · see citing works
“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).”
BackgroundUsing Machine Learning to Predict Dementia from Neuropsychiatric Symptom and Neuroimaging Data
Gill, S., Initiative, A. D. N., Mouchès, P., Hu, S., Rajashekar, D., MacMaster, F. P., Smith, E. E., Forkert, N. D., & Ismail, Z. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191169 · Cited by 116 · see citing works
“Thus, the MBI requirement for later life emergent and sustained NPS may better reflect true NPS that result from neurodegeneration and proteinopathies associated with dementia, removing symptoms that may be a result of non-dementia etiologies [38].”
BackgroundInfluentialPrevalence of Mild Behavioral Impairment and Risk of Dementia in a Psychiatric Outpatient Clinic
Matsuoka, T., Ismail, Z., & Narumoto, J. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190278 · Cited by 115 · see citing works
“According to previous reviews, depression in early life might be a risk factor for dementia, and late life onset of depression might be a prodromal symptom [4, 27].”
MethodMallo, S. C., Ismail, Z., Pereiro, A. X., Facal-Mayo, D., Lojo‐Seoane, C., Campos‐Magdaleno, M., & Juncos‐Rabadán, O. (2018) · International Psychogeriatrics · doi:10.1017/s1041610218000698 · Cited by 111 · see citing works
“Decreasing the likelihood of infections or other medical conditions, change in living situation or relationships, or medication adjustments and side effects contributing to NPS ascertainment likely results in fewer MBI false positives (Ismail et al., 2017a).”
BackgroundMethodInfluentialMatušková, V., Ismail, Z., Nikolai, T., Marková, H., Čechová, K., Nedelská, Z., Laczó, J., Wang, M., Hort, J., & Vyhnálek, M. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.643271 · Cited by 108 · see citing works
Depression and Dementia in Older Adults: A Neuropsychological Review
Tetsuka, S. (2021) · Aging and Disease · doi:10.14336/ad.2021.0526 · Cited by 111 · see citing works
“Despite the increasing evidence of an association between depression and dementia, the neuropathological mechanisms of depressive symptoms, which are predictive of the onset of dementia, have not yet been reliably elucidated [89].”
BackgroundPlasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment
Naude, J., Gill, S., Hu, S., McGirr, A., Forkert, N. D., Monchi, O., Stys, P. K., Smith, E. E., Ismail, Z., & Initiative, A. D. N. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200011 · Cited by 105 · see citing works
“Within the MBI diagnostic framework [10], relevant NPS are categorized into five domains, namely: decreased drive and motivation (apathy) [13], emotional dysregulation (mood and anxiety symptoms) [14], impulse dyscontrol (agitation, aggression, impulsivity, abnormal reinforcement, and reward) [15], social inappropriat…”
BackgroundBabulal, G. M., Roe, C. M., Stout, S. H., Rajasekar, G., Wisch, J. K., Benzinger, T. L. S., Morris, J. C., & Ances, B. M. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191078 · Cited by 103 · see citing works
“A previously described PET imaging protocol [32] was also completed for determining amyloid burden using the radiotracer [ 18 F]-Florbetapir (AV45).”
Creese, B., Griffiths, A. W., Brooker, H. J., Corbett, A., Aarsland, D., Ballard, C. G., & Ismail, Z. (2019) · International Psychogeriatrics · doi:10.1017/s1041610219001200 · Cited by 95 · see citing works
“…in functionally independent community dwelling older adults, in contrast to thoseNPS that aremore specific to dementia (e.g. resisting care, rummaging, and importuning); it has a reference period of 6 months rather than 2 to 4 weeks, as is the case with most other scales (Ismail et al., 2017a).”
BackgroundLanctôt, K. L., Ismail, Z., Bawa, K. K., Cummings, J. L., Masud Husain, B., Mortby, M. E., & Robert, P. H. (2023) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.5882 · Cited by 93 · see citing works
From Emotions to Mood Disorders: A Survey on Gait Analysis Methodology
Deligianni, F., Guo, Y., & Yang, G. (2019) · IEEE Journal of Biomedical and Health Informatics · doi:10.1109/jbhi.2019.2938111 · Cited by 90 · see citing works
“Furthermore, mild behavioral impairments, such as anxiety, irritability, euphoria and depression, they all have been associated with preclinical dementia syndromes [108].”
BackgroundAdaptation of the tail suspension test to the rat.
Chermat, R., Thierry, B., Micó, J. A., Stéru, L., & Simon, P. (1986) · PubMed · Cited by 91 · see citing works
CCCDTD5 recommendations on early non cognitive markers of dementia: A Canadian consensus
Montero‐Odasso, M., Pieruccini‐Faria, F., Ismail, Z., Li, K., Lim, A. S. P., Phillips, N. A., Kamkar, N., Sarquis‐Adamson, Y., Speechley, M. R., Theou, O., et al. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12068 · Cited by 75 · see citing works
Anxiety and risk of dementia: Systematic review and meta-analysis of prospective cohort studies
Santabárbara, J., Lipnicki, D. M., Villagrasa, B., Lobo, E., & López‐Antón, R. (2018) · Maturitas · doi:10.1016/j.maturitas.2018.10.014 · Cited by 77 · see citing works
Santabárbara, J., Lipnicki, D. M., Olaya, B., Villagrasa, B., Bueno‐Notivol, J., Nuez, L., López‐Antón, R., & Gracia‐García, P. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9061791 · Cited by 74 · see citing works
Creese, B., Arathimos, R., Brooker, H. J., Aarsland, D., Corbett, A., Lewis, C. M., Ballard, C. G., & Ismail, Z. (2021) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12164 · Cited by 68 · see citing works
Association of Alzheimer's genetic loci with mild behavioral impairment
Andrews, S. J., Ismail, Z., Anstey, K. J., & Mortby, M. E. (2018) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32684 · Cited by 67 · see citing works
“Thus, further research using the MBI-C is required, as the nature of the queries (i.e., later life onset of sustained symptoms) may be a very salient feature of dementia prognostication and early detection, when interventions may be more effective (Mortby, et al., 2018).”
BackgroundMethodInfluentialGoukasian, N., Hwang, K. S., Romero, T., Grotts, J., Do, T. M., Groh, J. R., Bateman, D. R., & Apostolova, L. G. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-031947 · Cited by 64 · see citing works
Self-citationFischer, C. E., Ismail, Z., Youakim, J. M., Creese, B., Kumar, S., Núñez, N. A., Darby, R. R., Vita, A. D., D’Antonio, F., de Lena, C., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190828 · Cited by 62 · see citing works
Dementia clinical trial implications of mild behavioral impairment
Mortby, M. E., Black, S. E., Gauthier, S. G., Miller, D., Porsteinsson, A. P., Smith, E. E., Ismail, Z., & Mortby, M. E. (2018) · International Psychogeriatrics · doi:10.1017/s1041610218000042 · Cited by 60 · see citing works
Han, F.-F., Wang, H., Wu, J.-J., Yao, W., Hao, C., & Pei, J.-J. (2021) · European Psychiatry · doi:10.1192/j.eurpsy.2021.2230 · Cited by 58 · see citing works
Yang, W., Li, X., Pan, K., Yang, R., Song, R., Qi, X., Pedersen, N. L., & Xu, W. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12303 · Cited by 57 · see citing works
Showraki, A., Murari, G., Ismail, Z., Barfett, J., Fornazzari, L., Muñoz, D. G., Schweizer, T. A., & Fischer, C. E. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190365 · Cited by 54 · see citing works
“Nosological constraints [32] and the lack of a standardized depression measurement method to distinguish chronic depression, history of depression, symptomatically-controlled depression and late life depression from each other, might also be another contributing factor.”
Wiels, W. A., Wittens, M. M. J., Zeeuws, D., Baeken, C., & Engelborghs, S. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.707580 · Cited by 52 · see citing works
“Nevertheless, distinguishing new neuropsychiatric symptoms of degenerative brain disease from preexisting (mild or subsyndromal) psychiatric issues remains challenging (67).”
BackgroundMcDade, E. (2022) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001131 · Cited by 49 · see citing works
Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status
Ghahremani, M., Smith, E. E., Chen, H., Creese, B., Goodarzi, Z., & Ismail, Z. (2023) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12404 · Cited by 50 · see citing works
Hudon, C., Escudier, F., Roy, J. D., Croteau, J., Cross, N. E., Dang‐Vu, T. T., Zomahoun, H. T. V., Grenier, S., Gagnon, J., Parent, A., et al. (2020) · Neuropsychology Review · doi:10.1007/s11065-020-09437-5 · Cited by 47 · see citing works
“The search strategy particularly focused on highly prevalent noncognitive symptoms in individuals in the pre-dementia phases of AD like depression, apathy, anxiety, and sleep difficulties (Apostolova & Cummings, 2008; Geda et al., 2014; Ismail et al., 2018).”
BackgroundThe Role of Gut Microbiota—Gut—Brain Axis in Perioperative Neurocognitive Dysfunction
Lu, J. G., Hou, W., Gao, S., Zhang, Y., & Zong, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.879745 · Cited by 43 · see citing works
“Patients with PND often present with a variety of neuropsychiatric symptoms like anxiety and depression, and anxiety and depression will accelerate the decline of their cognitive function (Ismail et al., 2018).”
BackgroundEbrahim, I., Ghahremani, M., Camicioli, R. M., Smith, E. E., & Ismail, Z. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.03.074 · Cited by 44 · see citing works
Cui, Y., Dai, S., Miao, Z., Zhong, Y., Liu, Y., Liu, L., Jing, D., Bai, Y., Kong, Y., Sun, W., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190113 · Cited by 43 · see citing works
“However, the rate of recognition of pre-existing psychiatric symptomatology in the clinic is still low and only a few studies use a scale for NPS as the screening standard, to date [17, 18].”
Neuropsychiatric symptoms in spinocerebellar ataxias and Friedreich ataxia.
Simona, K., Veronika, M., Zahinoor, I., & Martin, V. (2023) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105205 · Cited by 39 · see citing works
“Nonetheless, whether DSM criteria apply or not, depressive symptoms are debilitating and worth assessing and addressing (Ismail et al., 2018).”
BackgroundMallo, S. C., Valladares‐Rodríguez, S., Facal-Mayo, D., Lojo‐Seoane, C., Iglesias, M. J. F., & Pereiro, A. X. (2019) · International Psychogeriatrics · doi:10.1017/s1041610219001030 · Cited by 42 · see citing works
“Studies have suggested that the neuropathogenesis may differ based on the severity of the depressive symptomatology and the level of cognitive impairment (Ismail et al ., 2018).”
BackgroundRoss, A. B., Shertukde, S. P., Livingston Staffier, K., Chung, M., Jacques, P. F., & McKeown, N. M. (2023) · Advances in Nutrition · doi:10.1016/j.advnut.2023.04.003 · Cited by 41 · see citing works
Prevalence of mild behavioural impairment: a systematic review and meta‐analysis
Pan, Y., Shea, Y. F., Li, S., Chen, R., Mak, H. K., Chiu, P. K., Chu, L., & Song, Y. (2020) · Psychogeriatrics · doi:10.1111/psyg.12636 · Cited by 41 · see citing works
Matsuoka, T., Ueno, D., Ismail, Z., Rubinstein, E. B., Uchida, H., Mimura, M., & Narumoto, J. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210628 · Cited by 40 · see citing works
Menculini, G., Chipi, E., Paoletti, F. P., Gaetani, L., Nigro, P., Simoni, S., Mancini, A., Tambasco, N., Filippo, M. D., Tortorella, A., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094440 · Cited by 38 · see citing works
“Depression during the preclinical stages of AD and bvFTD can be often associated with other affective symptoms and mood changes [15,33].”
BackgroundAgitation and impulsivity in mid and late life as possible risk markers for incident dementia
Bateman, D. R., Gill, S., Hu, S., Foster, E. D., Ruthirakuhan, M. T., Sellek, A. F., Mortby, M. E., Matušková, V., Ng, K. P., Tarawneh, R. M., et al. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12016 · Cited by 37 · see citing works
Bell, E., Boyce, P. M., Porter, R., Bryant, R. A., & Malhi, G. S. (2021) · CNS Drugs · doi:10.1007/s40263-021-00823-y · Cited by 37 · see citing works
“This is also exemplified by adolescents, alluded to above, as typical changes in irritability across the lifespan often coincide with significant changes in neurobiological development and decline [9, 10].”
BackgroundFan, S., Liang, X., Yun, T., Pei, Z., Hu, B., Ismail, Z., Yang, Z., & Xu, F. (2020) · BMC Geriatrics · doi:10.1186/s12877-020-01903-2 · Cited by 36 · see citing works
Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression
Siafarikas, N., Kirsebom, B., Srivastava, D. P., Eriksson, C. M., Auning, E., Hessen, E., Selbæk, G., Blennow, K., Aarsland, D., & Fladby, T. (2021) · Scientific Reports · doi:10.1038/s41598-021-99794-9 · Cited by 36 · see citing works
Apathy and the Risk of Predementia Syndromes in Community-Dwelling Older Adults
Ceïde, M. E., Warhit, A., Ayers, E. I., Kennedy, G. J., & Verghese, J. (2020) · The Journals of Gerontology Series B · doi:10.1093/geronb/gbaa063 · Cited by 35 · see citing works
Xu, W., Wei, F., Shen, X., Bi, Y., Ma, Y., Li, J., Dong, Q., Tan, L., & Yu, J. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.07.004 · Cited by 35 · see citing works
“As common NPSs in older adults without dementia, depressive symptoms were proposed to be markers for prognostic utility of AD (3).”
Depressive disorders in the elderly and dementia: An update
Dias, N. S., Barbosa, I. G., Kuang, W., & Teixeira, A. L. (2020) · Dementia & Neuropsychologia · doi:10.1590/1980-57642020dn14-010001 · Cited by 33 · see citing works
Prevalence of mild behavioural impairment domains: a meta‐analysis
Pan, Y., Shea, Y. F., Ismail, Z., Mak, H. K., Chiu, P. K., Chu, L., & Song, Y. (2021) · Psychogeriatrics · doi:10.1111/psyg.12782 · Cited by 31 · see citing works
Ali, D. G., Bahrani, A. A., Barber, J. M., Khouli, R. H. E., Gold, B. T., Harp, J. P., Jiang, Y., Wilcock, D. M., & Jicha, G. A. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220294 · Cited by 31 · see citing works
“…neuropathological development of AD arguably begins with amyloid-(cid:2) (A (cid:2) ) deposition in the brain, which occurs many years before the appearance of cognitive decline (preclinical Alzheimer’s disease (pAD)) [3, 4], and has been identified as a risk factor for subsequent dementia [5, 6].”
Yoon, E. J., Lee, J., Kwak, S., & Kim, Y. K. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1051621 · Cited by 31 · see citing works
“This seems unexpected findings, because the above mentioned previous studies using NPI-Q identified associations of the risk of progression to dementia with depressed and affective clusters, moreover, accumulating evidence have suggested that affective and emotional symptoms are risk factors of cognitive decline and d…”
ResultTang‐Wai, D. F., Smith, E. E., Bruneau, M., Burhan, A. M., Chatterjee, A., Chertkow, H. M., Choudhury, S., Dorri, E., Ducharme, S., Fischer, C. E., et al. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12057 · Cited by 29 · see citing works
Hu, F., Hu, P., Chen, Y., Sun, H., Cai, J., He, X., Cao, Q., Yin, M., Zhang, Y., Li, Q., et al. (2023) · Theranostics · doi:10.7150/thno.81826 · Cited by 31 · see citing works
Ramezani, M., Ruskey, J. A., Martens, K., Kibreab, M., Javer, Z., Kathol, I., Hammer, T., Cheetham, J., Léveillé, E., Martino, D., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.587992 · Cited by 27 · see citing works
“, the origin of the study population, sex, and the fundamental issue of whether depression is chronic, recurrent, or of later life onset as most depression rating scales do not differentiate (8, 33).”
BackgroundHuang, M., Lee, W., Yeh, Y., Lin, Y., Lin, H., Wang, S., Yang, Y., Chen, C., & Fuh, J. (2021) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2021.12.004 · Cited by 27 · see citing works
Babulal, G. M., Zhu, Y., & Trani, J. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.12988 · Cited by 26 · see citing works
Zhang, K., Zhang, W., Wu, B., & Liu, S. (2020) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2020.104015 · Cited by 27 · see citing works
Gracia‐García, P., Bueno‐Notivol, J., Lipnicki, D. M., de la Cámara, C., Lobo, A., & Santabárbara, J. (2023) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.1934 · Cited by 26 · see citing works
Brain Metabolic Dysfunction in Early Neuropsychiatric Symptoms of Dementia
Ng, K. P., Chiew, H. J., Rosa‐Neto, P., Kandiah, N., Ismail, Z., & Gauthier, S. G. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01398 · Cited by 25 · see citing works
Arab, H. H., Khames, A., Alsufyani, S. E., El‐Sheikh, A. A. K., & Gad, A. M. (2023) · Pharmaceuticals · doi:10.3390/ph16020300 · Cited by 24 · see citing works
“In perspective, CRS in animals prompts behavioral despair evidenced by reduced sucrose intake, decrease in responsiveness to rewarding stimuli, and locomotor activity deficit [2,3,25].”
BackgroundADHD and Neurodegenerative Disease Risk: A Critical Examination of the Evidence
Becker, S., Sharma, M. J., & Callahan, B. L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.826213 · Cited by 24 · see citing works
“This is rather problematic in the context of examining relationships between ADHD and neurodegeneration, because ADHD-like experiences (inattention, distractibility, impulsivity, and emotional dysregulation) can be neuropsychiatric indicators of neurodegenerative disease onset (Ismail et al., 2018; Bateman et al., 202…”
BackgroundZhou, S., Wang, Q., Zhang, J., Wáng, Q., Hou, F., Han, X., Hu, S., Shen, G., & Zhang, Y. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.939150 · Cited by 23 · see citing works
Artificial neural networks-based classification of emotions using wristband heart rate monitor data
Chen, Y.-C., Hsiao, C.-C., Zheng, W.-D., Lee, R.-G., & Lin, R. (2019) · Medicine · doi:10.1097/md.0000000000016863 · Cited by 23 · see citing works
“Emotional changes may also present as prodromal symptoms of various psychiatric disorders [6] and neurodegenerative diseases.([7]) Neurotransmitters such as acetylcholine,([8]) serotonin, noradrenaline, and dopamine, are involved in the behavioral control([9]) of emotions.”
BackgroundEffects of Mindfulness-based Interventions on Dementia Patients: A Meta-analysis
Wang, F. L., Tang, Q. Y., Zhang, L. L., Yang, J., Li, Y., Peng, H., & Wang, S. H. (2020) · Western Journal of Nursing Research · doi:10.1177/0193945920916750 · Cited by 22 · see citing works
“Moreover, recent studies have found that emotional distress is not only a clinical symptom of dementia but may also be an important risk factor for the rapid development of mild cognitive impairment and preclinical Alzheimer’s disease to dementia (Ismail et al., 2018; Li & Li, 2018; Pietrzak et al., 2015).”
BackgroundRao, A. R., Chatterjee, P., Thakral, M., Dwivedi, S. N., & Dey, A. B. (2020) · PLoS ONE · doi:10.1371/journal.pone.0234514 · Cited by 23 · see citing works
“There are numerous mechanisms which try to explain the cognitive decline in individuals with diabetes mellitus, these include insulin dysregulation, pro-inflammatory pathways, vascular risk factors, oxidative stress and lipoprotein receptors[26], which are similar to the causal pathway between NPS and cognitive declin…”
BackgroundAnker, E., Ginsberg, Y., & Heir, T. (2021) · BMC Psychiatry · doi:10.1186/s12888-021-03223-0 · Cited by 22 · see citing works
Anxiety disorders, benzodiazepine prescription, and incident dementia
Brieler, J. A., Salas, J., Amick, M., Sheth, P., Garrett, E. K., Morley, J. E., & Scherrer, J. F. (2023) · Journal of the American Geriatrics Society · doi:10.1111/jgs.18515 · Cited by 22 · see citing works
“19 Inconsis-tent findings may be due to variations in how anxiety is measured and the degree of control for confounding factors.”
BackgroundChange in Purpose in Life Before and After Onset of Cognitive Impairment
Sutin, A. R., Luchetti, M., Stéphan, Y., & Terracciano, A. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.33489 · Cited by 22 · see citing works
Sun, Z., Ping, P., Li, Y., Feng, L., Liu, F., Zhao, Y., Yao, Y., Zhang, P., & Fu, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.870442 · Cited by 21 · see citing works
“, 2014), suggesting that with the development of the biological-psychological-social medical model, Qi depression caused by an accumulation of negative emotions has been proven to be closely related to the progression of cognitive decline (Zhou et al., 2006; Ismail et al., 2018; Zhang et al., 2021).”
BackgroundKwon, K. J., Kim, H. Y., Han, S., & Shin, C. Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111338 · Cited by 20 · see citing works
“This lack of efficacy may be attributed to the challenges in applying common psychiatric diagnostic criteria and clinical features to a population with neurodegenerative diseases [27].”
BackgroundRavona‐Springer, R., Heymann, A. D., Lin, H., Liu, X., Berman, Y., Schwartz, J., Soleimani, L., Sano, M. C., & Beeri, M. S. (2020) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2020.09.022 · Cited by 20 · see citing works
“This battery covers four cognitive domains: (1) Memory [Alzheimer’s Disease Assessment Scale (ADAS) Word List Immediate Recall, Delayed Recall, and Recognition], (2) Attention/ working memory [Diamond Cancellation, Digit Span forward, and backward], (3) Executive functions [Trails Making Test A and B, Digit Symbol Sub…”
BackgroundMethodLi, F., Kong, X., Zhu, H., Xu, H., Wu, B., Cao, Y., & Li, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1011510 · Cited by 20 · see citing works
“) in this study although they may be associated with cognitive function after stroke (Ismail et al., 2018; Weaver et al., 2021).”
BackgroundTurnbull, A. G., Anthony, M., Tadin, D., Porsteinsson, A. P., Heffner, K. L., & Lin, F. V. (2022) · Cortex · doi:10.1016/j.cortex.2022.10.015 · Cited by 20 · see citing works
The Dichotomy of Alzheimer’s Disease Pathology: Amyloid-β and Tau
Ashford, J. W. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181198 · Cited by 19 · see citing works
“Accordingly, some A PP related mechanisms which have an early, adverse effect on the function of the frontal lobe could lead to symptoms of mild behavioral impairment, including personality changes, apathy, and depression, which are related to prodromal and mild AD [72, 73].”
Atchison, K., Wu, P., Samii, L., Walsh, M., Ismail, Z., Iaboni, A., & Goodarzi, Z. (2024) · Age and Ageing · doi:10.1093/ageing/afae122 · Cited by 22 · see citing works
Liew, T. M., Yu, J., Mahendran, R., Ng, T. P., Kua, E. H., & Feng, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170947 · Cited by 18 · see citing works
“This finding is consistent with the current evidence that NPS in early NCD can be associated with worse cognitive outcome [27, 29, 30].”
Special Issue on mild behavioral impairment and non-cognitive prodromes to dementia
Mortby, M. E., Lyketsos, C. G., Geda, Y. E., & Ismail, Z. (2018) · International Psychogeriatrics · doi:10.1017/s1041610218000108 · Cited by 18 · see citing works
“In their paper relating depression and anxiety to cortical amyloid deposition in cognitively normal elderly, Krell-Roesch et al. (2018) provided evidence of an association between anxious and depressive symptoms and cortical amyloid deposition.”
BackgroundYao, C. W., Pelletier, A., Fereshtehnejad, S., Cross, N. E., Dang‐Vu, T. T., & Postuma, R. B. (2021) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.9562 · Cited by 17 · see citing works
Khoury, R., & Grossberg, G. T. (2018) · CNS Drugs · doi:10.1007/s40263-018-0590-9 · Cited by 17 · see citing works
Emotion dysregulation in idiopathic rapid eye movement sleep behavior disorder
Jun, J., Kim, R., Jung, H.-M., Byun, J., Seok, J. M., Kim, T., Lim, J., Sunwoo, J., Kim, H., Schenck, C. H., et al. (2019) · SLEEP · doi:10.1093/sleep/zsz224 · Cited by 17 · see citing works
Depressive Symptoms Are Associated with Cognitive Function in the Elderly with Type 2 Diabetes
Guerrero‐Berroa, E., Ravona‐Springer, R., Schmeidler, J., Heymann, A. D., Soleimani, L., Sano, M. C., LeRoith, D., Preiss, R., Zukran, R., Silverman, J. M., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170778 · Cited by 17 · see citing works
Harris, B., Roberts, B. R., DiMarco, G. M., Maldonado, K. A., Okwunwanne, Z., Savonenko, A., & Soto, P. (2022) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2022.114126 · Cited by 14 · see citing works
β-amyloid pathology is not associated with depression in a large community sample autopsy study
Saldanha, N. M., Suemoto, C. K., Rodriguez, R. D., Leite, R. E. P., Nascimento, C. F., Ferretti‐Rebustini, R. E. D. L., da Silva, M. M., Pasqualucci, C. A., Nitríni, R., Filho, W. J., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.09.062 · Cited by 16 · see citing works
Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment
Roberto, N., Portella, M., Marquié, M., Alegret, M., Hernández, I., Mauleon, A., Rosende-Roca, M., Abdelnour, C., de Antonio, E. E., Tartari, J., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.718949 · Cited by 17 · see citing works
The pathway to secondary prevention of Alzheimer's disease
McDade, E., Bednar, M. M., Brashear, H. R., Miller, D. S., Maruff, P., Randolph, C., Ismail, Z., Carrillo, M. C., Weber, C. J., Bain, L. J., et al. (2020) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12069 · Cited by 20 · see citing works
Mild behavioural impairment-apathy and core Alzheimer's disease cerebrospinal fluid biomarkers
Vellone, D. A., Leon, R., Goodarzi, Z., Forkert, N. D., Smith, E. E., & Ismail, Z. (2025) · Brain · doi:10.1093/brain/awaf194 · Cited by 14 · see citing works
“33 Furthermore, there might be slightly different effect sizes for biomarker associations with different MBI domains, dependent on the time course of domain emergence relative to the deposition of amyloid and the phosphorylation of tau.”
Chatzidimitriou, E., Ioannidis, P., Μoraitou, D., Konstantinopoulou, E., & Aretouli, E. (2023) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2023.1087765 · Cited by 15 · see citing works
“Irritability has also been reported as a common neuropsychiatric symptom and often as a pre-dementia risk marker (Ismail et al., 2018).”
BackgroundA narrative review on mild behavioural impairment: an exploration into its scientific perspectives
Cozza, M., & Boccardi, V. (2023) · Aging Clinical and Experimental Research · doi:10.1007/s40520-023-02472-1 · Cited by 16 · see citing works
Babulal, G. M., Chen, L., Murphy, S. A., Doherty, J. M., Johnson, A. M., & Morris, J. C. (2023) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2023.07.012 · Cited by 15 · see citing works
Li, E., Ai, F., Tian, Q., Yang, H., Tang, P., & Guo, B. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-06657-y · Cited by 15 · see citing works
“Depressive symptoms are widespread in older adults with cognitive impairment, and the overall comorbidity rate has reached 32% [3, 4].”
Ram, D., George, M., & Gowdappa, B. (2018) · Indian Journal of Psychiatry · doi:10.4103/psychiatry.indianjpsychiatry_183_18 · Cited by 14 · see citing works
“[17,18] Emotional dysregulation has been identified as a risk factor for cognitive impairment in adults.[19] Improving cognitive control over and persistence of emotional responses is often the target for cognitive-based psychotherapeutic approaches for the treatment of affective illnesses.”
BackgroundA Protective Role of Translocator Protein in Alzheimer’s Disease Brain
Jung, M. E. (2020) · Current Alzheimer Research · doi:10.2174/1567205017666200217105950 · Cited by 15 · see citing works
Imtiaz, D., Anwar, Y., & Khan, A. A. (2020) · Smart Health · doi:10.1016/j.smhl.2020.100140 · Cited by 14 · see citing works
Janicki, M. P., Hendrix, J. A., McCallion, P., & Panel, A. T. N. C. E. C. (2022) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12335 · Cited by 14 · see citing works
Ismail, Z., Gatchel, J. R., Bateman, D. R., Barcelos‐Ferreira, R., Cantillon, M., Jaeger, J., Donovan, N. J., & Mortby, M. E. (2018) · International Psychogeriatrics · doi:10.1017/s1041610218000637 · Cited by 14 · see citing works
Management of Psychiatric Symptoms in Dementia
Ayhan, Y., Yoseph, S. A., & Miller, B. L. (2022) · Neurologic Clinics · doi:10.1016/j.ncl.2022.05.001 · Cited by 13 · see citing works
Granata, N., Torlaschi, V., Zanatta, F., Giardini, A., Maestri, R., Pavesi, C., Sommaruga, M., Gazzi, L., Bertolotti, G., Braga, S. S., et al. (2022) · Psychology Health & Medicine · doi:10.1080/13548506.2022.2077394 · Cited by 13 · see citing works
“These data are in line with the existing literature about the prevalence of emotional distress in people with cognitive impairment (Ismail et al., 2018; Rock et al., 2014).”
ResultMarrie, R. A., Maxwell, C. J., Rotstein, D., Tsai, C.-C., & Tremlett, H. L. (2023) · Revue Neurologique · doi:10.1016/j.neurol.2023.07.002 · Cited by 12 · see citing works
Pierobon, A., Granata, N., Torlaschi, V., Vailati, C., Radici, A., Maestri, R., Pavesi, C., Sommaruga, M., Gazzi, L., Bertolotti, G., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0235570 · Cited by 12 · see citing works
“In fact, affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often revealing in advance neurodegenerative changes and a progressive cognitive decline [35].”
BackgroundEffect of Hearing Ability and Mild Behavioural Impairment on MoCA and Memory Index Scores
Gosselin, P. A., Ismail, Z., Faris, P., Benkoczi, C. L., Fraser, T. L., Cherry, S. W., Faulkner, T. I., & Islam, M. S. (2019) · Canadian Geriatrics Journal · doi:10.5770/cgj.22.374 · Cited by 12 · see citing works
“MoCA Memory Index 8(6-12) 11(9-14) 7(5-11) MWU=62 .”
BackgroundInfluentialInamura, K., Shinagawa, S., Nagata, T., Tagai, K., Nukariya, K., & Shigeta, M. (2022) · Psychogeriatrics · doi:10.1111/psyg.12818 · Cited by 11 · see citing works
- 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 › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Health Sciences › Medicine › Physiology › 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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