Browsing by Author "Mortby, Moyra E."

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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
    (Cambridge, 2018-02) Ismail, Zahinoor; Gatchel, Jennifer; Bateman, Daniel R.; Barcelos-Ferreira, Ricardo; Chantillon, Marc; Jaeger, Judith; Donovan, Nancy J.; Mortby, Moyra E.; Psychiatry, School of Medicine
    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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    Agitation and impulsivity in mid and late life as possible risk markers for incident dementia
    (Wiley, 2020-09-06) Bateman, Daniel R.; Gill, Sascha; Hu, Sophie; Foster, Erin D.; Ruthirakuhan, Myuri T.; Sellek, Allis F.; Mortby, Moyra E.; Matušková, Veronika; Ng, Kok Pin; Tarawneh, Rawan M.; Freund‐Levi, Yvonne; Kumar, Sanjeev; Gauthier, Serge; Rosenberg, Paul B.; Oliveira, Fabricio Ferreira de; Devanand, D. P.; Ballard, Clive; Ismail, Zahinoor; Psychiatry, School of Medicine
    To identify knowledge gaps regarding new‐onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre‐dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late‐onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitive decline and dementia. This scoping review of agitation and impulsivity pre‐dementia syndromes summarizes the current biomedical literature in terms of epidemiology, diagnosis and measurement, neurobiology, neuroimaging, biomarkers, course and prognosis, treatment, and ongoing clinical trials. Validations for pre‐dementia scales such as the MBI Checklist, and incorporation into longitudinal and intervention trials, are needed to better understand impulse dyscontrol as a risk factor for mild cognitive impairment and dementia.
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    Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials
    (Elsevier, 2022-02) Mortby, Moyra E.; Adler , Lawrence; Agüera-Ortiz , Luis; Bateman, Daniel R.; Brodaty , Henry; Cantillon , Marc; Geda , Yonas E.; Ismail, Zahinoor; Lanctôt, Krista L.; Marshall, Gad A.; Padala, Prasad R.; Politis, Antonios; Rosenberg, Paul B.; Siarkos, Kostas; Sultzer, David L.; Theleritis, Christos; ISTAART NPS PIA; Psychiatry, School of Medicine
    Apathy is one of the most prevalent, stable and persistent neuropsychiatric symptom across the neurocognitive disorders spectrum. Recent advances in understanding of phenomenology, neurobiology and intervention trials highlight apathy as an important target for clinical intervention. We conducted a comprehensive review and critical evaluation of recent advances to determine the evidence-based suggestions for future trial designs. This review focused on 4 key areas: 1) pre-dementia states; 2) assessment; 3) mechanisms/biomarkers and 4) treatment/intervention efficacy. Considerable progress has been made in understanding apathy as a treatment target and appreciating pharmacological and non-pharmacological apathy treatment interventions. Areas requiring greater investigation include: diagnostic procedures, symptom measurement, understanding the biological mechanisms/biomarkers of apathy, and a well-formed approach to the development of treatment strategies. A better understanding of the subdomains and biological mechanisms of apathy will advance apathy as a treatment target for clinical trials.