Estimating Gender Differences in the Association between Cognitive Resilience and MCI Incidence.

INTRODUCTION: Recent evidence suggests that the influence of verbal intelligence and education on the onset of subjective cognitive decline may be modulated by gender, where education contributes less to cognitive resilience in women than in men. This study aims to examine gender differences in the association between cognitive resilience (CR) and mild cognitive impairment (MCI) incidence in an Australian population-based cohort. METHODS: We included 1806 participants who had completed at least the first two waves and up to four waves of assessments in the Personality and Total Health (PATH) through life study (Baseline: 49% Female, Mage=62.5, SD=1.5), age range=60-66). CR proxies included measures of educational attainment, occupation skill, verbal intelligence, and leisure activity. Discrete-time survival analyses were conducted to examine gender differences in the association between CR proxies and MCI risk, adjusting for age and Apolipoprotein E4 status. RESULTS: Gender differences were only found in the association between occupation and MCI risk, where lower occupation skill was more strongly associated with higher risk in men than in women (OR = 1.30, 95% CI[1.07, 1.57]). In both genders, after adjusting for education and occupation, one SD increase in leisure activity was associated with lower MCI risk by 24% (OR = 0.76, 95% CI[0.65, 0.89]). Higher scores in verbal intelligence assessment were associated with reduced risk of MCI by 22% (OR = 0.78, 95% CI[0.69, 0.89]). CONCLUSION: Occupational experience may contribute to cognitive resilience differently between genders. Life-course cognitive engagement and verbal intelligence may be more protective against MCI than education and occupation for both men and women.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS: We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION: The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

Apathy as a determinant of health behaviors in older adults: Implications for dementia risk reduction.

INTRODUCTION: Long-term improvements in physical inactivity and other behavioral risk factors are integral to dementia risk reduction; however, sustained behavior change is challenging. Apathy, depression, and fatigue may impact engagement in health behaviors, but their presentation overlaps. This study investigates whether these symptoms are differentially associated with multiple health behaviors. METHODS: In 1037 community-dwelling older adults without dementia (aged 70-90, 55% women), regression analyses examined apathy, depression, and fatigue as predictors of health behaviors (physical activity, diet, alcohol, smoking) and a behavioral risk index. RESULTS: Apathy was associated with reduced physical activity and alcohol use, and one or multiple behavioral risk factors. No or inconsistent relations were found between depression or fatigue and health behaviors. DISCUSSION: Apathy is relevant to multiple health behaviors and should be considered when designing health promotion for older adults, including interventions for dementia risk reduction. Findings highlight the importance of distinguishing apathy from comorbid symptoms. Highlights: Novel theory-based perspective on behavioural risk factors for dementia.Higher apathy predicted less physical activity and alcohol use, and increased odds of lifestyle risk factors.Depressive symptoms were not associated with any health behavior.Apathy may be a determinant of multiple health behaviors in older adults, distinct from depression and fatigue.Considering apathy in precision prevention of dementia appears warranted.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMH) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well-documented in populations of different ethnicities and/or from different geographical regions. METHOD: Magnetic resonance imaging data of five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1,946) were examined for WMH and their associations with vascular risk factors and cognition. RESULT: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake and insufficient physical activity. Participants with moderate or higher physical activity had less WMH than those who never exercised, but the former two groups did not differ. Hypertension and stroke had stronger associations with WMH volumes in the White, compared to Asian subsample. DISCUSSION: The current study highlighted the ethnic differences in the contributions of vascular risk factors to WMH.

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment-related aspects of apathy from depression in neurocognitive disorders.

OBJECTIVES: This narrative review describes the clinical features of apathy and depression in individuals with neurocognitive disorders (NCDs), with the goal of differentiating the two syndromes on the basis of clinical presentation, diagnostic criteria, neuropathological features, and contrasting responses to treatments. METHODS: Literature was identified using PubMed, with search terms to capture medical conditions of interest; additional references were also included based on our collective experience and knowledge of the literature. RESULTS: Evidence from current literature supports the distinction between the two disorders; apathy and depression occur with varying prevalence in individuals with NCDs, pose different risks of progression to dementia, and have distinct, if overlapping, neurobiological underpinnings. Although apathy is a distinct neuropsychiatric syndrome, distinguishing apathy from depression can be challenging, as both conditions may occur concurrently and share several overlapping features. Apathy is associated with unfavorable outcomes, especially those with neurodegenerative etiologies (e.g., Alzheimer's disease) and is associated with an increased burden for both patients and caregivers. Diagnosing apathy is important not only to serve as the basis for appropriate treatment, but also for the development of novel targeted interventions for this condition. Although there are currently no approved pharmacologic treatments for apathy, the research described in this review supports apathy as a distinct neuropsychiatric condition that warrants specific treatments aimed at alleviating patient disability. CONCLUSIONS: Despite differences between these disorders, both apathy and depression pose significant challenges to patients, their families, and caregivers; better diagnostics are needed to develop more tailored treatment and support.

The impact of mild cognitive impairment on decision-making under explicit risk conditions: Evidence from the Personality and Total Health (PATH) Through Life longitudinal study.

OBJECTIVE: Previous research has indicated that cognition and executive function are associated with decision-making, however the impact of mild cognitive impairment (MCI) on decision-making under explicit risk conditions is unclear. This cross-sectional study examined the impact of MCI, and MCI subtypes, on decision-making on the Game of Dice Task (GDT), among a cohort of older adults. METHOD: Data from 245 older adult participants (aged 72-78 years) from the fourth assessment of the Personality and Total Health Through Life study were analyzed. A diagnostic algorithm identified 103 participants with MCI, with subtypes of single-domain amnestic MCI (aMCI-single; n = 38), multi-domain amnestic MCI (aMCI-multi; n = 31), and non-amnestic MCI (n = 33), who were compared with an age-, sex-, education-, and income-matched sample of 142 cognitively unimpaired older adults. Decision-making scores on the GDT (net score, single number choices, and strategy changes) were compared between groups using nonparametric tests. RESULTS: Participants with MCI showed impaired performance on the GDT, with higher frequencies of single number choices and strategy changes. Analyses comparing MCI subtypes indicated that the aMCI-multi subtype showed increased frequency of single number choices compared to cognitively unimpaired participants. Across the sample of participants, decision-making scores were associated with measures of executive function (cognitive flexibility and set shifting). CONCLUSION: MCI is associated with impaired decision-making performance under explicit risk conditions. Participants with impairments in multiple domains of cognition showed the clearest impairments. The GDT may have utility in discriminating between MCI subtypes.

Who displays dementia-related stigma and what does the general public know about dementia? Findings from a nationally representative survey.

OBJECTIVES: To identify the characteristics of those who tend to hold stigmatising beliefs and behaviours towards people living with dementia to inform dementia education and the targeting of interventions to reduce dementia-related stigma.A nationally representative telephone survey of 1000 Australians aged 18-93 years was conducted to assess general knowledge of dementia and dementia-related stigma. A single open-ended question was used to assess participants' general knowledge of dementia. Modified items from the Lay Public Dimension of the Family Stigma in Alzheimer's Disease Scale were used to assess dementia-related stigma.Only 26% of participants demonstrated good dementia knowledge while almost half of the participants had a mixed understanding of dementia. Dementia-related negative cognitive attributions were found to be higher in (1) the older age cohorts, (2) amongst individuals who know someone with dementia, (3) speak a language other than English at home, and (4) have a better understanding of dementia. Older age cohorts, men, those who do not know someone with dementia, and those who speak a non-English language at home also reported significantly higher discriminatory behavioural reactions compared to the younger age cohorts, females, those who know someone with dementia, and those who speak English only at home.This study identifies a need for improved public education about dementia. A structured approach to the development of strategies that is specifically tailored to different age, gender and cultural groups may provide a beneficial approach to help improve dementia knowledge and reduce dementia-related stigma in the population.

Residential aged care staff perceptions and responses towards neuropsychiatric symptoms: a mixed methods analysis of electronic healthcare records.

OBJECTIVES: To investigate electronic care notes to better understand reporting and management of neuropsychiatric symptoms (NPS) by residential aged care (RAC) staff. METHODS: We examined semi-structured care notes from electronic healthcare notes of 77 residents (67% female; aged 67-101; 79% with formal dementia diagnosis) across three RAC facilities. As part of standard clinical practice, staff documented the NPS presentation and subsequent management amongst residents. Using a mixed-method approach, we analyzed the type of NPS reported and explored care staff responses to NPS using inductive thematic analysis. RESULTS: 465 electronic care notes were recorded during the 18-month period. Agitation-related behaviors were most frequently reported across residents (48.1%), while psychosis (15.6%), affective symptoms (14.3%), and apathy (1.3%) were less often reported. Only 27.5% of the notes contained information on potential causes underlying NPS. When faced with NPS, care staff responded by either providing emotional support, meeting resident's needs, removing identified triggers, or distracting. CONCLUSION: Results suggest that RAC staff primarily detected and responded to those NPS they perceived as distressing. Findings highlight a potential under-recognition of specific NPS types, and lack of routine examination of NPS causes or systematic assessment and management of NPS. These observations are needed to inform the development and implementation of non-pharmacological interventions and care programs targeting NPS in RAC.Supplemental data for this article is available online at https://doi.org/10.1080/13607863.2022.2032597 .

Mixed Evidence of an Association between Self-Rated Hearing Difficulties and Falls: Prospective Analysis of Two Longitudinal Studies.

INTRODUCTION: This study aimed to assess the extent to which a single item of self-reported hearing difficulties is associated with future risk of falling among community-dwelling older adults. METHODS: We used data from two Australian population-based cohorts: three waves from the PATH Through Life study (PATH; n = 2,048, 51% men, age 66.5 ± 1.5 SD years) and three waves from the Concord Health and Ageing in Men Project (CHAMP; n = 1,448, 100% men with mean age 77.3 ± 5.3 SD years). Hearing difficulties were recorded on a four-point ordinal scale in PATH and on a dichotomous scale in CHAMP. The number of falls in the past 12 months was reported at each wave in both studies. In CHAMP, incident falls were also ascertained by triannual telephone call cycles for up to four years. Multivariable-adjusted random intercept negative binomial regression models were used to estimate the association between self-reported hearing difficulties and number of falls reported at the following wave or 4-monthly follow-ups. RESULTS: In PATH, self-reported hearing difficulties were associated with a higher rate of falls at follow-up (incidence rate ratio = 1.15, 95% CI = 1.03-1.27 per a one-level increase in self-reported hearing difficulties), after adjusting for sociodemographic characteristics, health behaviours, physical functioning, balance, mental health, medical conditions, and medications. There were no significant associations between hearing difficulties and the rate of falls based on either repeated survey or 4-monthly follow-ups in CHAMP. CONCLUSION: Though we find mixed results, findings from PATH data indicate an ordinal measure of self-reported hearing loss may be predictive of falls incidence in young-old adults. However, the null findings in the male-only CHAMP preclude firm conclusions of a link between hearing loss and falls risk.

Psychosis as a Treatment Target in Dementia: A Roadmap for Designing Interventions.

Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials.

Sex differences in neuropsychiatric symptoms in Alzheimer's disease dementia: a meta-analysis.

BACKGROUND: Neuropsychiatric symptoms (NPS) are common in individuals with Alzheimer's disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia. METHODS: Literature searches were conducted in Embase, MEDLINE/PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar from inception to February 2021. Study selection, data extraction, and quality assessment were conducted in duplicate. Effect sizes were calculated as odds ratios (OR) for NPS prevalence and Hedges' g for NPS severity. Data were pooled using random-effects models. Sources of heterogeneity were examined using meta-regression analyses. RESULTS: Sixty-two studies were eligible representing 21,554 patients (61.2% females). The majority of the included studies had an overall rating of fair quality (71.0%), with ten studies of good quality (16.1%) and eight studies of poor quality (12.9%). There was no sex difference in the presence of any NPS (k = 4, OR = 1.35 [95% confidence interval 0.78, 2.35]) and overall NPS severity (k = 13, g = 0.04 [- 0.04, 0.12]). Regarding specific symptoms, female sex was associated with more prevalent depressive symptoms (k = 20, OR = 1.60 [1.28, 1.98]), psychotic symptoms (general psychosis k = 4, OR = 1.62 [1.12, 2.33]; delusions k = 12, OR = 1.56 [1.28, 1.89]), and aberrant motor behavior (k = 6, OR = 1.47 [1.09, 1.98]). In addition, female sex was related to more severe depressive symptoms (k = 16, g = 0.24 [0.14, 0.34]), delusions (k = 10, g = 0.19 [0.04, 0.34]), and aberrant motor behavior (k = 9, g = 0.17 [0.08, 0.26]), while apathy was more severe among males compared to females (k = 11, g = - 0.10 [- 0.18, - 0.01]). There was no association between sex and the prevalence and severity of agitation, anxiety, disinhibition, eating behavior, euphoria, hallucinations, irritability, and sleep disturbances. Meta-regression analyses revealed no consistent association between the effect sizes across studies and method of NPS assessment and demographic and clinical characteristics. DISCUSSION: Female sex was associated with a higher prevalence and greater severity of several specific NPS, while male sex was associated with more severe apathy. While more research is needed into factors underlying these sex differences, our findings may guide tailored treatment approaches of NPS in AD dementia.

Diastolic Blood Pressure Variability in Later Life May Be a Key Risk Marker for Cognitive Decline.

BACKGROUND: There is an increasing awareness of the need to understand the interaction between long-term blood pressure patterns and their impact on the brain and cognition. METHODS: Our aim was to investigate the relationship between repeated blood pressure measures and change in cognitive performance over 12 years and imaging data at 12 years using a longitudinal population study. The data consisted of 2 cohorts, one midlife and one later life. Using linear regression, we examined the relationship between blood pressure (systolic, diastolic, change in blood pressure between visits, and visit-to-visit variability), change in cognitive performance and imaging at 12 years. RESULTS: Data on cognitive change were available in 1054 at midlife, baseline age 42.7 (SD 1.5) and 1233 in later life, 62.5 (1.5) years. Imaging data were available in 168 and 233, respectively. After adjustment for multiple comparisons greater diastolic blood pressure variability in later life was associated with a -1.95 point decline (95% CI, -2.89 to -1.01) on an attention-based task and a -0.42 point (95% CI, -0.68 to -0.15) decline in performance on a psychomotor task. A higher SD in diastolic pressure across follow-up was associated with greater white matter hyperintensity volume (%increase per 10 mm Hg increase in the SD [1.50 (95% CI, 1.16-1.94]). CONCLUSIONS: In a largely normotensive/mildly hypertensive population, our analyses reported no relationships between blood pressure and cognition in midlife but a potential role for diastolic blood pressure variability in later life as a risk marker for cognitive decline. This may indicate an at-risk period or a means to identify an at-risk population at the age where diastolic pressure is starting to decline.

Non-pharmacological interventions for neuropsychiatric symptoms of dementia in residential aged care settings: An umbrella review.

BACKGROUND: Prevalence of neuropsychiatric symptoms amongst people living with dementia in residential aged care is high. Their presence is associated with poorer quality of life for residents and higher burden of care for staff. Existing reviews have not focused on the evaluation of efficacy of non-pharmacological interventions in specific population settings (community vs. residential aged care). OBJECTIVES: To determine the efficacy of non-pharmacological interventions to manage neuropsychiatric symptoms of dementia in residential aged care settings. DESIGN: An umbrella review was conducted. DATA SOURCES: PubMed/Medline, Embase, Cochrane Library and Web of Science were searched for eligible reviews in December 2019, February 2020 and June 2021. METHODS: Two authors independently screened titles and abstracts, and assessed full-text reviews for eligibility. The quality of reviews was appraised with 'AMSTAR-2: A Measurement tool to assess systematic reviews'. Narrative summaries grouped findings by intervention domains. RESULTS: From 1362 systematic reviews identified, 26 met the inclusion criteria. Of these, 10 focused on person tailored interventions, six on sensory stimulation interventions, three on environmental interventions, three on exercise interventions, and four on multiple intervention types. Quality ratings identified reviews to be of mostly moderate quality (73%). The majority or reviews reported positive results but not all were statistically significant. Tailored interventions that included music and social elements appeared to be most beneficial for depressive symptoms and mood. Furthermore, outcome measures and intervention protocols were highly heterogeneous across interventions. CONCLUSIONS: The findings of this umbrella review suggest that combining different types of interventions and tailoring them to the personal experiences of the resident is recommended. A more standardised approach for outcome measures used is vital to assess efficacy and allow comparison of future non-pharmacological interventions.

Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials.

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.

Gender differences in cognitive development in cohorts of young, middle, and older adulthood over 12 years.

Understanding gender differences in human cognitive development may contribute to understanding the gender differences in outcomes in cognitive ageing. However, evaluation of this topic has been hindered by a lack of representative, longitudinal data from different aged cohorts measured on the same cognitive tests. Gender differences in cognitive abilities were evaluated in three population-based cohorts (baseline age-span 20 to 76, 52% female, 94% Caucasian, 5% Asian and 1% other ethnic background, baseline N = 7,485), initially drawn from the electoral role in Australia where voting is compulsory, that were assessed four times over 12 years on measures of verbal memory, processing speed, working memory, verbal ability, and reaction time. Linear mixed models showed that within each cohort, women had better verbal memory and men had better working memory and faster reaction times. Verbal ability and processing speed showed variable gender differences in the young and middle-aged cohorts but no difference in the oldest cohort. In young and middle age, there were no gender differences in rates of change in verbal memory, processing speed, reaction time, verbal ability, or working memory. In old age, the gender differences were only observed in rates of change in verbal memory. Women showed more verbal memory decline between the 8-year and 12-year follow-ups than men, despite retaining higher average memory performance than men. We conclude that from ages 20-76, gender differences in cognitive abilities are stable except for faster memory ageing among women in the eighth decade. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Association of sex differences in dementia risk factors with sex differences in memory decline in a population-based cohort spanning 20-76 years.

Sex differences in late-life memory decline may be explained by sex differences in dementia risk factors. Episodic memory and dementia risk factors were assessed in young, middle-aged and older adults over 12 years in a population-based sample (N = 7485). For men in midlife and old age, physical, cognitive and social activities were associated with less memory decline, and financial hardship was associated with more. APOE e4 and vascular risk factors were associated with memory decline for women in midlife. Depression, cognitive and physical activity were associated with memory change in older women. Incident midlife hypertension (ß = - 0.48, 95% CI - 0.87, - 0.09, p = 0.02) was associated with greater memory decline in women and incident late-life stroke accounted for greater memory decline in men (ß = - 0.56, 95% CI - 1.12, - 0.01), p = 0.05). Women have fewer modifiable risk factors than men. Stroke and hypertension explained sex differences in memory decline for men and women respectively.

Agitation and impulsivity in mid and late life as possible risk markers for incident dementia.

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.