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.

Center for Alzheimer Research Division of Clinical Geriatrics Department of Neurobiology Care Sciences and Society Karolinska Institute Stockholm Sweden

Centre for Addiction and Mental Health Toronto Ontario Canada

College of Medicine and Health The University of Exeter Exeter UK

Community Health Sciences and O'Brien Institute for Public Health University of Calgary Calgary Alberta Canada

Department of Clinical Neurosciences; and the Ron and Rene Ward Centre for Healthy Brain Aging Research; Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada

Department of Neurology and Neurosurgery Escola Paulista de Medicina Federal University of São Paulo São Paulo São Paulo Brazil

Department of Neurology College of Medicine The Ohio State University Columbus Ohio USA

Department of Neurology National Neuroscience Institute Singapore Singapore

Department of Pharmacology and Toxicology University of Toronto Ontario Canada

Department of Psychiatry and the Mathison Centre for Mental Health Research and Education Cumming School of Medicine University of Calgary Calgary Alberta Canada

Department of Psychiatry Indiana University School of Medicine Indianapolis Indiana

Department of Psychiatry University of Toronto Ontario Canada

Division of Geriatric Psychiatry and Neuropsychiatry Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore Maryland

Hurvitz Brain Sciences Research Program Sunnybrook Research Institute Toronto Ontario Canada

Indiana University Center for Aging Research Regenstrief Institute Indianapolis Indiana

International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic

McGill Center for Studies in Aging McGill University Montreal Quebec Canada

Memory Disorders Clinic Department of Neurology 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Prague Czech Republic

Neuroscience Research Australia University of New South Wales Sydney New South Wales Australia

New York State Psychiatric Institute and Department of Psychiatry and Department of Psychiatry College of Physicians and Surgeons Columbia University New York New York

Ruth Lilly Medical Library Indiana University School of Medicine Indianapolis Indiana

School of Medical Sciences Örebro University Örebro Sweden

School of Psychology University of New South Wales Sydney New South Wales Australia

The Alzheimer Foundation of Costa Rica Costa Rica

University of California Berkeley Berkeley CA

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ClinicalTrials.gov, Identifier: NCT03108846, Escitalopram for Agitation in Alzheimer's Disease. Bethesda (MD): National Library of Medicine (US).

ClinicalTrials.gov, Identifier: NCT03031184, Study of Mirtazapine for Agitation in Dementia. Bethesda (MD): National Library of Medicine (US).

ClinicalTrials.gov, Identifier: NCT04075435, Cannabidiol Solution for the Treatment of Behavioral Symptoms in Older Adults With Alzheimer's Dementia. Bethesda (MD): National Library of Medicine (US).

ClinicalTrials.gov, Identifier: NCT02792257, Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimer's Disease (AD) (THC‐AD). Bethesda (MD): National Library of Medicine (US).

ClinicalTrials.gov, Identifier: NCT03710642, Prazosin for Agitation in Alzheimer's Disease. Bethesda (MD): National Library of Medicine (US).

ClinicalTrials.gov, Identifier: NCT03548584, A Trial to Evaluate the Safety, Efficacy, and Tolerability of Brexpiprazole in Treating Agitation Associated With Dementia of the Alzheimer's Type. Bethesda (MD): National Library of Medicine (US).

ClinicalTrials.gov, Identifier: NCT03393520, Assessment of the Efficacy, Safety, and Tolerability of AVP‐786 (Deudextromethorphan Hydrobromide [d6‐DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type. Bethesda (MD): National Library of Medicine (US).

ClinicalTrials.gov, Identifier: NCT02129348, Treatment of Psychosis and Agitation in Alzheimer's Disease. Bethesda (MD): National Library of Medicine (US).

Mild Behavioral Impairment Is Associated With Atrophy of Entorhinal Cortex and Hippocampus in a Memory Clinic Cohort