Assessing cognitive function in longitudinal studies of ageing worldwide: some practical considerations.

Over 55 million people live with dementia worldwide. With 40% of modifiable risk factors estimated to contribute to dementia, the potential for prevention is high, and preventive measures, at an early stage of cognitive decline, are likely to positively influence future dementia trends. Countries need reliable health data and adequate measurement tools to quantify, monitor and track early changes in cognitive capacity in the general population. Many cognitive tests exist; however, there is no consensus to date about which instruments should be employed, and important variations in measurement have been observed. In this narrative review, we present a number of cognitive tests that have been used in nationally representative population-based longitudinal studies of ageing. Longitudinal panel studies of ageing represent critical platforms towards capturing the process of cognitive ageing and understanding associated risk and protective factors. We highlight optimal measures for use at a population level and for cross-country comparisons, taking into consideration instrument reliability, validity, duration, ease of administration, costs, literacy and numeracy requirements, adaptability to sensory and fine motor impairments and portability to different cultural and linguistic milieux. Drawing upon the strengths and limitations of each of these tests, and the experience gained and lessons learnt from conducting a nationally representative study of ageing, we indicate a comprehensive battery of tests for the assessment of cognitive capacity, designed to facilitate its standardised operationalisation worldwide.

A systematic review of the measurement properties of aspects of psychological capacity in older adults.

OBJECTIVE: to examine the measurement properties of instruments that have been used to measure aspects of psychological capacity in adults aged 60 years and over. METHODS: the databases PsycINFO, MEDLINE, EMCARE and Scopus from 2010 were searched using search terms related to psychological capacity, older persons and measurement properties. Both data extraction and risk-of-bias assessment were conducted using the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) criteria using Covidence software. RESULTS: the full text of 326 articles were reviewed and a total of 30 studies were included, plus two further articles identified from reference lists (n = 32). No single instrument measuring psychological capacity was identified. Twenty (n = 20) instruments were identified that measure seven constructs of psychological capacity: Resilience; Sense of coherence; Hope; Mindfulness; Optimism; Attachment to life; Emotional regulation. CONCLUSIONS: this systematic review identified potential measures of psychological capacity in older adults. The review will inform further work to develop a single comprehensive measure of psychological capacity in older adults.

The worldwide costs of dementia in 2019.

INTRODUCTION: Dementia is a leading cause of death and disability globally. Estimating total societal costs demonstrates the wide impact of dementia and its main direct and indirect economic components. METHODS: We constructed a global cost model for dementia, presenting costs as cumulated global and regional costs. RESULTS: In 2019, the annual global societal costs of dementia were estimated at US $1313.4 billion for 55.2 million people with dementia, corresponding to US $23,796 per person with dementia. Of the total, US $213.2 billion (16%) were direct medical costs, US $448.7 billion (34%) direct social sector costs (including long-term care), and US $651.4 billion (50%) costs of informal care. DISCUSSION: The huge costs of dementia worldwide place enormous strains on care systems and families alike. Although most people with dementia live in low- and middle-income countries, highest total and per-person costs are seen in high-income countries. HIGHLIGHTS: Global economic costs of dementia were estimated to reach US $1313.4 in 2019. Sixty-one percent of people with dementia live in low-and middle-income countries, whereas 74% of the costs occur in high-income countries. The impact of informal care accounts for about 50% of the global costs. The development of a long-term care infrastructure is a great challenge for low-and middle-income countries. There is a great need for more cost studies, particularly in low- and middle-income countries. Discussions of a framework for global cost comparisons are needed.

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

Dementia and caregiver burden: A three-year longitudinal study.

OBJECTIVES: Dementia, with its progressive cognitive and functional decline and associated neuropsychiatric symptoms, places a large burden on caregivers. While frequently studied, longitudinal findings about the overall trajectory of burden are mixed. The study sought to characterize caregiver burden over a 3-year period and identify predictors of this burden. METHODS: Seven-hundred-and-eighty-one patients with dementia were recruited from nine memory clinics around Australia. Measures of caregiver burden, cognition, function, and neuropsychiatric symptoms were completed with patients and their caregivers at regular intervals over a 3-year period. Patients' level of services and medication use were also recorded. RESULTS: Of the 720 patients with measures of caregiver burden at baseline, 47.4% of caregivers had clinically significant levels of burden. This proportion increased over time, with 56.8% affected at 3 years. Overall levels of burden increased for caregivers of patients without services, though did not change for caregivers of patients receiving services or residential care after controlling for other variables. Patient characteristics-including greater neuropsychiatric symptoms, lower functional ability, fewer medications, lack of driving ability-and female sex of caregivers were associated with greater burden. CONCLUSIONS: High levels of caregiver burden are present in a large proportion of caregivers of people with dementia and this increases over time for those without services. Clinical characteristics of patients (including neuropsychiatric symptoms, function, overall health, driving status), level of services, and caregiver sex appear to be the best predictors of this burden. These characteristics may help identify caregivers at greater risk of burden to target for intervention.

Online training and support program (iSupport) for informal dementia caregivers: protocol for an intervention study in Portugal.

BACKGROUND: Informal caregivers (IC) of people with dementia (PwD) are at greater risk of developing physical and mental health problems when compared to the general population and to IC of people with other chronic diseases. Internet-based interventions have been explored for their potential to minimize the negative effects of caring, accounting for their ubiquitous nature, convenient delivery, potential scalability and presumed (cost) effectiveness. iSupport is a self-help online program developed by the World Health Organization (WHO) to provide education, skills training and support to IC of PwD. This paper describes the design of an intervention study aimed at determining the effectiveness of a Portuguese culturally adapted version of iSupport on mental health and other well-being outcomes. METHODS: The study follows an experimental parallel between-group design with two arms: access to the five modules and twenty-three lessons of "iSupport" for three months (intervention group); or access to an education-only e-book (comparison group). One hundred and eighty four participants will be recruited by referral from national associations. Inclusion criteria are: being 18 years or older and provide e-consent; being a self-reported non-paid caregiver for at least six months; of a person with a formal diagnosis of dementia; being skilled to use internet; and experience a clinically relevant level of burden (≥ 21 on Zarit Burden Interview) or depression or anxiety symptoms (≥ 8 on Hospital Anxiety and Depression Scale). Data is collected online, resorting to self-administered instruments, at baseline, 3 and 6 months after baseline. The primary outcome is caregiver burden, measured by the Zarit Burden Interview. Symptoms of depression and anxiety, quality of life, positive aspects of caregiving and general self-efficacy are secondary study outcomes. The data analysis will follow an Intention-to-treat (ITT) protocol. DISCUSSION: This protocol is an important resource for the many organizations in several countries aiming to replicate iSupport. Findings from this intervention study will offer evidence to bolster an informed decision making on scaling up iSupport as a new intervention program with minimal costs aimed at minimizing the psychological distress of IC of PwD in Portugal and elsewhere. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04104568. Registered 26 September 2019.

Mild Cognitive Impairment and Caregiver Burden: A 3-Year-Longitudinal Study.

OBJECTIVES: Mild cognitive impairment (MCI) is common, affecting 10%-35% of people over 65, and poses unique challenges for patients and their caregivers. Comparatively little research has examined caregiver burden in this population, with longitudinal research, in particular, lacking. We examined caregiver burden in a sample of people with MCI over 3 years. DESIGN: Three-year observational study. SETTING: Nine memory clinics in Australia. PARTICIPANTS: One-hundred-and-eighty-five people with MCI and their caregivers. MEASUREMENTS: Measures of caregiver burden, cognition, function, neuropsychiatric symptoms, driving status, and medication use were completed with patients and their caregivers at regular intervals over a 3-year period. RESULTS: Between 21.1% and 29.5% of caregivers reported a clinically significant level of burden over the study. Patients' higher levels of neuropsychiatric symptoms, lower functional ability, and lack of driving ability, and caregivers' employment were associated with greater caregiver burden over time. Caregiver burden did not increase over time when controlling for patient and caregiver characteristics. CONCLUSIONS: High levels of caregiver burden are present in a significant proportion of caregivers of people with MCI. Clinical characteristics of patients - including severity of neuropsychiatric symptoms and functional impairment - and the employment status of caregivers predict burden. Such characteristics may help identify caregivers at greater risk of burden to target for intervention.

Validity and reliability of the Persian version of general practitioner assessment of cognition (P-GPCOG).

Objectives: The study aimed to examine the validity, reliability, and practicality of the Persian version of the General Practitioner Assessment of Cognition (P-GPCOG) as a brief, efficient cognitive assessment instrument in Iranian older adults. Method: The sample comprised 151 community-dwelling older adults and 79 nursing home residents (aged ≥60 years). The English GPCOG was translated, back-translated, and revised to prepare the final P-GPCOG. The Abbreviated Mental Test score (AMTs) and the Depression in Old Age Scale (DIA-S) were administered to the two different samples to establish the convergent and discriminant validity of the P-GPCOG. Results: The mean age of the sample was 70.67 (SD = 9.51); 57.4% were male. The mean P-GPCOG scores for the total, cognitive and informant subscales were 7.67 (SD = 4.59), 4.18 (SD = 2.73), and 3.49 (SD = 2.24), respectively. Cognitive (P < 0.001), informant (P < 0.001) and total scores (P < 0.001) differed significantly between community-dwelling participants and nursing home residents. Worse cognitive performance on the P-GPCOG correlated significantly with worse scores on the AMTs (r = 0.61, P < 0.001) and less so with depressive symptoms as measured with the DIA-S (r = -0.20, P < 0.05). Cronbach's alpha for the P-GPCOG cognitive and informant subscales were 0.90 and 0.83 respectively, indicating a high degree of internal consistency and homogeneity between items. The test-retest correlation for the total P-GPCOG score was 0.82 in 30 participants after 19 days. P-GPCOG cognitive scores correlated significantly with education. Conclusion: The P-GPCOG displayed strong psychometric properties, offering healthcare professionals a quick and efficient cognitive instrument for older Persian speakers. As with other cognitive assessment tools, the P-GPCOG cognitive score is affected by a person's level of education.

The stability of neuropsychiatric subsyndromes in Alzheimer's disease.

INTRODUCTION: Neuropsychiatric symptoms are common in Alzheimer's disease. Previous research has attempted to identify subsyndromes-sets of symptoms related to one another-to clarify underlying mechanisms and treatment targets. We examined the stability of these subsyndromes over time. METHODS: We administered the Neuropsychiatric Inventory annually for 3 years to 447 patients with Alzheimer's disease recruited from memory clinics. We conducted principal component analyses at each time point and multiple-group confirmatory factor analyses across time. RESULTS: Principal component analyses showed that no two time points shared the same factor structure. Factor solutions did not exhibit strong simple structures and substantial cross-loadings were common. Confirmatory analysis revealed significant differences in factor loadings and model fit over time. DISCUSSION: Symptoms cannot be neatly partitioned into discrete clusters that are stable over time. The findings highlight the significant challenges that clinicians and caregivers face and may help explain the lack of success in intervention studies.

The prevalence and causes of younger onset dementia in Eastern Sydney, Australia.

BACKGROUND: Service planning for people with younger onset dementia (YOD; an onset of symptoms before the age of 65 years) relies on prevalence estimates, with existing models based upon older people. This pilot study investigated the prevalence and causes of YOD in a defined catchment area of Eastern Sydney, Australia. METHODS: The study was conducted in three stages: publicity building, case finding, and case validation. A brief structured questionnaire was sent to health professionals in the catchment area asking how many patients with YOD they had seen over the previous 12 months. Memory clinics and hospital records were also searched for YOD patients. Clinicians assigned a Statistical Linkage Key to each patient to prevent double counting, and indicated the cause of dementia. The majority of patients were validated by a review of medical case notes. Prevalence data were calculated for the following age groups: 30-64, 30-44, and 45-64 years. RESULTS: Two hundred and four potential patients were identified, of which 141 met inclusion criteria. The primary clinical subtypes were alcohol-related dementia (18.4%), Alzheimer's disease (17.7%), vascular dementia (12.8%), and frontotemporal dementia (11.3%). Eighty-eight patients were aged 30 to 64 years on census date and were therefore included in the prevalence calculations. The overall prevalence was 68.2 per 100,000 population at risk for the 30-64-year age group (95% Confidence Interval (CI): 54.9-83.4); 11.6 per 100,000 for the 30-44-year age group (95% CI: 5.3-21.7); and 132.9 per 100,000 for the 45-64 age group (95% CI: 105.8-164.2). CONCLUSIONS: Younger onset dementia affects a significant number of people in Eastern Sydney with a diverse range of clinical types. This prevalence rate is higher than previous reports from the United Kingdom and Japan, with a different distribution of etiologies, which have important implications for service planning for this group.

Correlates of psychological distress in study partners of older people with and without mild cognitive impairment (MCI) - the Sydney Memory and Ageing Study.

OBJECTIVES: Psychological effects of supporting someone with mild cognitive impairment (MCI) are often overlooked. We aimed to establish correlates of psychological distress in study partners of individuals with and without nonclinical MCI. METHODS: Demographic, psychosocial and health measures were obtained cross-sectionally from 714 participants (39% MCI) and study partners of a longitudinal community-based study on cognitive aging. Study partners (i.e. family members/friends) were categorized as providing support with instrumental everyday activities or not. Psychological distress was measured by the Kessler psychological distress scale. Multiple hierarchical regressions examined determinants of psychological distress within Pearlin's stress process model. RESULTS: Psychological distress was generally low and not associated with MCI or whether study partners provided support or not. Instead, distress was greater if participants were male irrespective of study partners' sex and if study partners reported negative reactions to participants' behavioral symptoms, felt burdened by providing support and showed worse coping abilities; overall explaining 37% variance. Self-rated disability and aspects of health-related quality of life explained additional 7%. CONCLUSION: Objective impairment measures were not associated with distress in partners or supporters. However, study partners' appraisals of functional and behavioral symptoms were linked to increased distress even in this very mildly affected community cohort.

Validation of the General Practitioner Assessment of Cognition - Chinese version (GPCOG-C) in China.

BACKGROUND: To assess the reliability, validity, and diagnostic utility of the Chinese version of General Practitioner Assessment of Cognition (GPCOG-C). The GPCOG, which is specifically designed for use in primary care to screen for cognitive impairment, consists of a patient section testing cognition, and an informant section asking about decline in cognitive and functional abilities. METHODS: The English version of GPCOG was translated, back-translated, and subsequently revised to determine the final GPCOG-C. Our sample comprised 253 community-dwelling volunteers with memory concerns aged 50 years and over and 103 outpatients of a psychogeriatric clinic with memory complaints. Participants were assessed by one of the four general practitioners or six psychogeriatricians. The Mini-Mental State Examination (MMSE), the Hasegawa's Dementia Scale (HDS), and the GPCOG-C were compared against the DSM-IV-defined dementia diagnosis. RESULTS: The internal consistency (Cronbach's α) was 0.68 for the GPCOG patient section. The test-retest was 0.98 for the GPCOG-C total. The sequential administration of both components of GPCOG-C had a sensitivity of 97% and a specificity of 89%, with a positive predictive value of 72% and a negative predictive value of 99%. Both the GPCOG-C total and sequential two-stage scoring methods performed at least well as the MMSE and HDS in detecting dementia. The administration time for the two-stage approach was 4.3 ± 2.4 min. CONCLUSIONS: The GPCOG-C is a valid, time efficient instrument for dementia screening in China.

Sydney Memory and Ageing Study: an epidemiological cohort study of brain ageing and dementia.

Non-demented community-dwelling older adults aged 70-90 years (n = 1,037) randomly recruited from the electoral roll completed neuropsychological and medical assessments over six years. The overall prevalence of mild cognitive impairment (MCI) at baseline was 36.7%. Risk factors for MCI include APOE ε4 allele carrier status, high homocysteine, heart disease, poor odour identification, low visual acuity and low mental activity, but notable age and sex differences were observed. Neuropsychiatric symptoms were rare; depression was the most common and was associated with cognitive impairment in at least one domain as well as subsequent dementia 2 years later. Poorer cognitively demanding functional abilities were associated with cognitive impairment. Biomarkers for cognitive impairment and decline were identified. Inflammatory markers and plasma apolipoprotein levels were associated with poorer performance in the attention/processing speed domain. Measures of white matter lesions, white matter integrity, sulcal morphology and tractography were identified as novel biomarkers of early cognitive decline. Stronger deactivation in the posteromedial cortex with increasing memory load on functional MRI predicted future decline. Compared to previous reports, our prevalence rates of MCI were higher but rates of progression to dementia and reversion to normal were similar, as were risk factors for progression to dementia.

Predictors and outcomes for caregivers of people with mild cognitive impairment: a systematic literature review.

BACKGROUND: Dementia caregiving is strongly linked to depression, anxiety, and burden in caregivers. Little is known about whether the same holds for people supporting an older person with mild cognitive impairment (MCI). We aim to systematically review the current evidence for negative caregiver outcomes in MCI using Pearlin and colleagues' stress process model as a theoretical framework. METHODS: Widely used scientific literature databases were searched using MCI- and caregiver-related terms with "AND" relations. Results were limited to quantitative English language articles published in peer-reviewed journals between 1980 and November 2010. RESULTS: Of the 266 identified articles, six reported relevant depression data on 988 MCI caregivers (73% spouses). The pooled Center for Epidemiologic Studies Depression scale (CES-D) mean score was 12.95 (standard deviation = 6.16). The pooled depression prevalence (i.e., CES-D score ≥ 16 or equivalent) was 23%. Two studies compared depression in MCI and dementia caregivers, indicating higher levels in dementia caregivers. Other outcomes, such as burden, stress, or anxiety, were only investigated by individual studies precluding pooling of data. Similarly, pooling of the data on the predictors of caregiver outcomes was impossible because of data heterogeneity. However, descriptive analysis of predictors revealed that Pearlin and colleagues' caregiver stress process model at least partially applies to the MCI context. CONCLUSIONS: The studies reviewed were all cross sectional in design, involving clinical samples, thus limiting generalizability. Depression and psychological comorbidity, although not as pronounced as in dementia caregivers, are common complications in MCI caregivers. The long-term course of outcomes in MCI caregivers requires further investigation.

A Systematic Review of Quality Dementia Clinical Guidelines for the Development of WHO's Package of Interventions for Rehabilitation.

BACKGROUND AND OBJECTIVES: As part of the WHO Rehabilitation 2030 call for action, the WHO Rehabilitation Programme is developing its Package of Interventions for Rehabilitation (PIR) to support ministries of health around the globe in integrating rehabilitation services into health systems. As a vital step for this PIR development, we conducted a systematic review of clinical practice guidelines (CPGs) for dementia to identify interventions for rehabilitation and related evidence. RESEARCH DESIGN AND METHODS: Following WHO Rehabilitation Programme and Cochrane Rehabilitation's methodology, quality CPGs published in English between January 2010 and March 2020 were identified using PubMed, Embase, CINAHL, PEDro, Google Scholar, guideline databases, and professional society websites. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation (II). RESULTS: Of the 22 CPGs that met the selection criteria, 6 satisfied the quality evaluation. Three hundred and thirty rehabilitation-related recommendations were identified, mostly concentrated in the areas of cognition, emotion, and carer support. There were many strong interventions, with moderate- to high-quality evidence that could be easily introduced in routine practice. However, major limitations were found both in the quality of evidence and scope, especially in areas such as education and vocation, community and social life, and lifestyle modifications. DISCUSSION AND IMPLICATIONS: Further rigorous research is needed to build quality evidence in dementia rehabilitation in general, and especially in neglected areas for rehabilitation. Future work should also focus on the development of CPGs for dementia rehabilitation. A multipronged approach is needed to achieve Universal Health Coverage for dementia rehabilitation.

Pre-existing neurological conditions and COVID-19 co-infection: Data from systematic reviews, meta-analyses, and scoping reviews.

BACKGROUND: Pre-existing neurological diseases have been identified as risk factors for severe COVID-19 infection and death. There is a lack of comprehensive literature review assessing the relationship between pre-existing neurological conditions and COVID-19 outcomes. Identification of high risk groups is critical for optimal treatment and care. METHODS: A literature review was conducted for systematic reviews, meta-analyses, and scoping reviews published between January 1, 2020 and January 1, 2023. Literature assessing individuals with pre-existing neurological diseases and COVID-19 infection was included. Information regarding infection severity was extracted, and potential limitations were identified. RESULTS: Thirty-nine articles met inclusion criteria, with data assessing >3 million patients from 51 countries. 26/51 (50.9%) of countries analyzed were classified as high income, while the remaining represented middle-low income countries (25/51; 49.0%). A majority of evidence focused on the impact of cerebrovascular disease (17/39; 43.5%) and dementia (5/39; 12.8%) on COVID-19 severity and mortality. 92.3% of the articles (36/39) suggested a significant association between neurological conditions and increased risk of severe COVID-19 and mortality. Cerebrovascular disease, dementia, Parkinson's disease, and epilepsy were associated with increased COVID severity and mortality. CONCLUSION: Pre-existing neurological diseases including cerebrovascular disease, Alzheimer's disease and other dementias, epilepsy, and Parkinson's disease are significant risk factors for severity of COVID-19 infection and mortality in the acute infectious period. Given that 61.5% (24/39) of the current evidence only includes data from 2020, further updated literature is crucial to identify the relationship between chronic neurological conditions and clinical characteristics of COVID-19 variants.

Pharmacologic treatment of apathy in dementia.

Apathy in patients with dementia is common, underrecognized, and undertreated. We sought to improve understanding of the pharmacologic treatment of apathy in dementia by performing a systematic literature review of studies that used apathy outcome scales to document results of pharmacologic treatments for apathy. There is limited evidence of efficiency of pharmacotherapy for treatment of apathy in dementia. The best results were found for acetylcholinesterase inhibitors. There was some evidence of efficacy for memantine, but less evidence of efficacy for stimulants, calcium antagonists, and antipsychotics. There was no evidence to support the use of antidepressants or anticonvulsants. The research quality of studies was modest. Recommendations for standardizing research and for holistic evaluation and treatment are provided.

Dementia time to death: a systematic literature review on survival time and years of life lost in people with dementia.

BACKGROUND: Life expectancy with dementia directly influences rates of prevalence and service needs and is a common question posed by families and patients. As well as years of survival, it is useful to consider years of life lost after a diagnosis of dementia. METHODS: We systematically reviewed the literature on mortality and survival with dementia which were compared to estimated life expectancies in the general population. Both were then compared by age (under 65 years vs. 65+ years), gender, dementia type, severity, and two epochs (prior to and after introduction of cholinesterase inhibitors in 1997). RESULTS: Survival after a diagnosis of dementia varies considerably and depends on numerous factors and their complex interaction. Relative loss of life expectancy decreases with age at diagnosis across varying gender, dementia subtypes (except for frontotemporal dementia and dementia with Lewy bodies), and severity stages. Numerous study deficiencies precluded a meta-analysis of survival in dementia. CONCLUSION: Estimates of years of life lost through dementia may be helpful for patients and their families. Recommendations for future research methods are proposed.

Brain health as a global priority.

Brain health is an evolving concept that has become increasingly popular within clinical and academic centers, journalism and the general public. It can be defined as the state of brain functioning across cognitive, sensory, social-emotional, behavioural and motor domains, allowing a person to realize their full potential over the life course. Multiple, interconnected determinants play a role in shaping brain health from pre-conception through the end of life. Brain health can be optimized by addressing the following determinants: physical health, healthy environments, safety and security, learning and social connection, and access to quality services. Optimizing brain health improves brain structure and functioning across all domains and benefits health by lowering rates of neurological disorders, mental health conditions, and substance use; improving quality of life for people with lived experience of these conditions; and improving physical health (particularly through improved endocrine and immunological functioning and lower rates of stress-related physical health conditions). Additionally, optimizing brain health can lead to social and economic benefits including increased school retention and academic achievement, lower rates of teenage pregnancies, lower rates of incarceration, lower health care costs and rates of disability, higher productivity, and greater wealth. Optimizing brain health for all is paramount to ensuring human health and well-being globally. It is central to achieving global commitments outlined in the Intersectoral global action plan on epilepsy and other neurological disorders 2022-2031, WHO's Triple Billion targets, the UN SDGs and the 2021 Geneva Charter for Well-being. Efforts to optimize brain health require multi-stakeholder collaborations and must be integrated across all sectors of society: health and social care; education; legislature and governance; finance and economy; employment; infrastructure, urban planning and housing; and ecology, nature and climate. In return, robust investments in actions that optimize brain health across the life course promise to improve multiple health outcomes and lift development and well-being globally. Multisectoral engagement and collaboration are urgently needed in order to move the brain health agenda forward for all people.