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When do cognitive impairments emerge in patients with schizophrenia?

PsychQuiz: Cognition in Schizophrenia

 for significant procognitive effects for antipsychotics and other pharmacologic approaches.

 Therefore, treatment of cognitive impairment in schizophrenia represents a tremendous area of unmet need.

 on the effects of exercise on brain structure and functional performance.

 found that aerobic exercise exerted a positive effect on global cognition and some, but not all, cognitive domains in patients with schizophrenia. Unfortunately, findings are limited by small samples, as well as variable types and intensity of exercise and study designs.

“Mrs Morris” is a 48-year-old Black woman with a history of chronic schizophrenia. During hospitalization for an episode of illness exacerbation, her antipsychotic medication was modified. Over the next 4 months, she gained approximately 50 lb. Mrs Morris declined to lower the dose of her antipsychotic or change medications because of her clinical improvement. She worried about risk of another illness relapse. However, she was receptive to the recommendation for increased physical activity for weight loss.

Mrs Morris started walking with a neighbor for about 30 minutes at a moderate pace at least 3 times per week. Over the next year, she lost 36 lb. Although there were no clinically appreciable changes in her cognitive function, she reported feeling better as a result of her exercise regimen.

 performed a 12-week randomized controlled trial of the effects of aerobic walking on cognitive function in patients with schizophrenia.

 The goal was to determine if the intensity of aerobic walking is associated with changes in cognition. Patients were randomized 1:1 based on age and sex to usual treatment with antipsychotics with or without aerobic walking. Inclusion criteria were 20 to 60 years, DSM-5 diagnosis of schizophrenia, stable antipsychotic dose for at least 1 month, Positive and Negative Syndrome Scale (PANSS) total score < 95, no history of major physical illness, and no physical disability that caused difficulty walking.

The program comprised 150 minutes/week of outdoor walking, typically divided over 3 to 5 sessions and each with a 5-minute warm-up, followed by a 5-minute cool-down. Transportation was provided to the exercise sessions as needed. Participants wore a Fitbit to monitor heart rate and exercise intensity and were supervised by research staff who provided guidance based on heart rate. The patients could rest if needed. Participants were stratified into high- and low-intensity groups based on the average in-session heart rate reserve. Cognition was evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS).

Data were analyzed using intention-to-treat and per-protocol analyses. Multivariate general linear model repeated measures were used to investigate the effects of time, group, and the time x group interaction on cognition, controlling for illness duration. The authors randomized 67 patients to treatment as usual (TAU, n = 34) or aerobic walking (n = 33) who completed the baseline assessment. Thirty-three patients in the TAU and 31 in the aerobic walking group completed the 12-week trial (

). At baseline, participants in the aerobic walking group scored approximately 0.5 standard deviations lower on 

 than the TAU group. The mean duration of aerobic walking was 129 minutes/week. Eleven patients achieved high-intensity walking and 22 maintained low-intensity. In the entire intent-to-treat sample, the authors found a trend for a group effect for greater improvement in verbal fluency in the aerobic walking group. They also found a significant group effect on attention and processing speed in high- versus low-intensity aerobic walking.

This was the first trial of the effects of aerobic walking and exercise intensity on 

in schizophrenia, according to the study authors. Most (> 90%) patients completed the trial with a mean of 3 days of exercise per week. The findings suggest that this intervention is feasible and acceptable to patients, and that supervision and transportation are associated with retention. Study limitations included the modest sample size (especially in the high-intensity group) and a relatively short study duration, as well as the inability for blinding to the intervention.

A supervised aerobic walking program involving moderate-intensity exercise is feasible and acceptable in patients with schizophrenia. Higher intensity aerobic exercise may have modest procognitive effects in these patients. Considering the other health benefits of aerobic walking, these programs can be useful for patients with schizophrenia.

is a professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for 

. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain & Behavior Research Foundation, and the Stanley Medical Research Institute.

Pharmacological cognitive enhancement in schizophrenia

The magic of movement; the potential of exercise to improve cognition

Rosenbaum S, et al. Aerobic exercise improves cognitive functioning in people with schizophrenia: a systematic review and meta-analysis

Effects of aerobic walking on cognitive function in patients with schizophrenia: a randomized controlled trial

An earlier version of this article was published online as 

Exercise and Cognition in Schizophrenia: Is There a Link?

 This article appeared in the March 2021 print issue of 

Aerobic exercise has been found to exert a positive effect on global cognition and some, but not all, cognitive domains in patients with schizophrenia.

Is There a Link Between Exercise, Cognition, and Schizophrenia

First recognized in 1872 by George Huntington, MD, 

 (HD) is a neurodegenerative disorder that is characterized by progressive decline in motor functioning, cognition, and behaviors.

 In North America, approximately 30,000 individuals have this 

, and an additional 150,000 individuals are at risk for developing it.

 HD tends to occur more commonly among individuals of European descent, with a prevalence rate of 10 to 15 per 100,000. The incidence of HD is approximately 4.7 to 6.9 

 per million per year in the Western population.

 The median age of diagnosis for HD is approximately 40 years.

 It is rare for HD to be diagnosed among individuals 20 years or younger, or among individuals 65 years or older. HD affects men and women equally.

The neuropathological hallmark among individuals with HD is the progressive atrophy of caudate nucleus and putamen due to neuronal loss.

 The clinical features of HD occur due to the loss of medium-sized projection spiny neurons in the dorsal striatum, which express the dopaminergic type 1 or 2 receptors. As the illness progresses, global neuronal loss and generalized cerebral atrophy occur, and the overall brain weight can decrease by up to 40%. These medium-sized projection spiny neurons use the inhibitory transmitter γ-aminobutyric acid and either dynorphin, enkephalin, or substance P as cotransmitters. It is thought that the loss of inhibitory input from the medium-sized spiny neurons, which usually exert an inhibitory effect, is the reason for the uncontrolled movements characteristic of individuals with HD. Individuals with HD also have intranuclear inclusions and protein aggregates in the dystrophic neurons of both the striatum and 

 Additionally, the number of cortical inclusions correlates directly with the length of the CAG repeat expansion and the age of onset of the illness. Furthermore, these intranuclear inclusions tend to appear before the loss in brain weight. The loss of brain weight precedes the loss of body weight and the onset of neurological symptoms.

There is significant variability in the type, timing, and progression of clinical symptoms.

 The clinical course can be divided into premanifest and 

 The premanifest period can be further divided into presymptomatic and prodromal periods. During the presymptomatic period, which is approximately 10 to 15 years before the onset of symptoms, individuals are not clinically distinguishable from those individuals without HD. During the prodromal period, individuals present with subtle motor, cognitive, and behavioral symptoms. Once individuals enter the manifest period with prominent motor, cognitive, and behavioral symptoms, the symptoms continue to progress and worsen, and the illness is ultimately fatal. The median survival time from the 

The symptoms of HD can be divided into 2 broad categories: progressive motor symptoms and neuropsychiatric symptoms.

A diagnosis of HD is made only when the characteristic motor features manifest, even among individuals who are gene positive.

The motor symptoms of HD can be divided into 2 main categories: abnormal involuntary movements and impaired voluntary movements.

 Among individuals with HD, the most common abnormal movements are characteristic of chorea, which is among the early presenting symptoms, especially among individuals with adult-onset HD. 

 are more common among individuals with earlier-onset HD (younger than 21 years).

 They are seen among patients with adult-onset HD during the severe stages of the illness. Impaired voluntary movements include motor incoordination, bradykinesia, rigidity, dystonia, gait disturbances, and eye movement abnormalities.

 Dysarthria and dysphagia are seen in later stages of the illness, often leading to choking and aspiration. 

 describes common treatments for motor symptoms.

Neuropsychiatric symptoms are often present well before the motor symptoms manifest, sometimes decades prior, and include depression, irritability/aggression, executive dysfunction (eg, apathy, obsessive-compulsive behaviors), psychosis, cognitive decline, and dementia.

Individuals with the HD gene who are presymptomatic exhibit a higher prevalence of neuropsychiatric symptoms.

 Neuropsychiatric complaints are the presenting symptom in approximately half of individuals. Among symptomatic individuals, more than 70% have neuropsychiatric symptoms, with symptoms often waxing and waning. 

 are often multifactorial in origin and are considered to be the most burdensome symptoms for caregivers and family members.

In a study of 1993 individuals with HD mutations from 15 European countries, 73% of the participants had some neuropsychiatric symptom within the past month.

 Moderate to severe apathy and depression were seen in 28.1% and 12.7% of the participants, respectively. Similarly, irritable and aggressive symptoms were present in 13.9% of the participants, and 13.2% of the participants showed obsessive/compulsive behaviors (OCBs). However, moderate to severe psychotic symptoms were found in only 1.2% of the participants. Apathy was more prevalent in advanced stages of the disease (11% in early stages vs 54.6% in advanced stages); it may be the only neuropsychiatric symptom that is linearly related to progressive neurodegeneration. Additionally, the presence of all neuropsychiatric symptoms during the previous month was associated with a positive psychiatric history, and a past episode of depression was particularly associated with 

 Depressed mood, loss of interest, guilt, and suicidality were more indicative of depression than somatic symptoms (eg, poor appetite, sleep disturbances, and psychomotor slowing).

 In patients with HD, depression is more common among women.

 Independent correlates of depression include a positive psychiatric history for 

, OCBs, a previous suicide attempt, and the use of benzodiazepines or antidepressants.

Suicidal ideation is also common in individuals with HD (

 According to a recent review, lifetime rates of suicide attempts range from 6.4% to 16%, and the percentage of deaths from suicide range from 2.2% to 10%. The risk factors include the presence of psychiatric comorbidities, especially depression, followed by anxiety, aggression, and previous suicide attempt. Other related risk factors include irritability, apathy, OCBs, psychosis, history of suicidal ideation, alcohol abuse, and the use of antidepressants. No consistent evidence showed that the risk for 

 was associated with sex, ethnicity, having children, history of incarceration, severity of motor dysfunction, disease stage, and specific neuronal loss or pathophysiologic circuit.

Examining the neuropsychiatric symptoms in a European HD cohort (REGISTRY) study, 24.7% of individuals with HD reported mild irritability/aggression, and 13.9% reported moderate to severe irritability/aggression.

 The prevalence of moderate to severe irritability and aggression increased as disease stage progressed, from 10.4% in the milder stages to 19.6% in the later stages. Independent correlates included male sex, younger age, history of depression, psychosis, and a previous suicide attempt.

 One review found the prevalence of OCBs ranged from 5% to 52%, whereas perseverative behaviors (PBs) occurred in approximately 75% of the individuals.

 Individuals with premanifest HD reported more OCBs when compared with gene-negative controls. However, individuals with manifest HD reported a higher rate of OCBs when compared with those with premanifest HD. Both OCBs and PBs are associated with duration and severity of HD, but they tend to decrease in the most advanced stage of the disease. A formal diagnosis of 

 is also more prevalent than in the general population, and it is often classified as “obsessive-compulsive and related disorders due to another medical condition” using the DSM-5 criteria. OCBs tend to cause significant distress and impairment in functioning. PBs often occur without the individual’s full awareness or insight into their occurrence.

 A recent study of 7966 participants with manifest HD found that 12.95% had a history of psychosis.

 Only 2.83% of participants with premanifest HD had a history of psychosis. The mean age of psychosis onset was 48.34 years, and these individuals had mild-to-moderate psychosis. A family history of 

 in a first-degree relative was documented in 27.5% of participants with psychosis. Factors associated with psychosis in manifest HD included lower education level, unemployment, single marital status, depression, decreased verbal fluency score, and decreased total functional capacity. Psychosis was also associated with younger age of clinical HD diagnosis and younger age of motor symptom onset, and it was correlated with a general decrease in cognitive capacity.

 Available evidence indicates that between 13% and 71% of individuals may present with symptoms of anxiety.

 can occur at any stage of the disorder, including the prodromal stage, but it does not appear to be a measure of disease progression.

 Anxiety may present as generalized anxiety, social anxiety, anticipatory anxiety, or panic, or as 

, and it may co-occur with depression. Anxiety may occur as a result of environmental factors as well as cognitive and physical impairments. It can also be confused with akathisia, which occurs as a result of medications (eg, antipsychotics or tetrabenazine) used to treat HD symptoms.

 Approximately 90% of individuals report sleep problems, including insomnia, difficulties in falling asleep, frequent nocturnal awakenings, and excessive daytime sleepiness.

 Available evidence indicates that some sleep disorders are found in the early phase of the disease, even during the illness’ premanifest stage. These disorders may be associated with comorbid psychiatric disorders, especially mood and anxiety disorders. Involuntary movements and increased motor activity may also contribute to 

. Many drugs that are used to improve the core symptoms of HD may also contribute to sleep disturbances, including amantadine, clonazepam, diazepam, L-DOPA olanzapine, quetiapine, riluzole, sodium valproate, tetrabenazine, deutetrabenazine, and venlafaxine.

 Due to the degenerative nature of HD, individuals develop gradually progressive cognitive decline.

 Individuals develop the prototypical frontal-subcortical type of dementia, with frontal-executive disturbances, attentional deficits, and reductions in processing speed.

 These symptoms are the result of striatal and thalamic degeneration as well as degeneration in the caudate nucleus and putamen. As the illness progresses, abnormalities in visuomotor integration, visual perception, mental rotation, language production, and organization occur. However, the rate of progression of cognitive decline varies significantly among individuals, suggesting that other mechanisms (including environmental and genetic variables) may contribute to the neuropathological and clinical progression of cognitive decline.

Available evidence indicates a comprehensive and multidisciplinary approach is required. Given the complexity of the illness’ clinical presentation, it should be treated by a group of providers including physicians, nurses, occupational and speech therapists, physical therapists, and social workers.

 Both nonpharmacological and pharmacological management strategies have benefited individuals with HD-associated neuropsychiatric symptoms.

 The use of nonpharmacological treatment strategies often complements pharmacological treatments. A thorough 

 assessment can assist in identifying the environmental and medical triggers and causes of neuropsychiatric symptoms, which then can be used in developing individualized treatment plans. Cognitive dysfunction can be reduced by structured daily schedules, providing cues, and having regular routines. In addition, respite care may significantly relieve caregiver burden.

There are no controlled trials for the pharmacotherapy of neuropsychiatric manifestations of HD, but evidence has been gathered from published case reports, case series, and an expert-based consensus guideline (

HD is a progressive and often fatal neurodegenerative disorder that is associated with severe motor and neuropsychiatric manifestations. The neuropsychiatric manifestations of HD can occur decades before the motor symptoms of HD become apparent, and they are associated with pathological changes that occur within the striatum and cortical regions of the brain, including the frontal lobes. Only apathy appears to be linearly related to the progressive neurodegeneration associated with HD. These manifestations are associated with significant disabilities and cause distress to both the individual with HD and their caregivers.

Currently, there are no disease-modifying strategies for the treatment of individuals with HD. Available treatment strategies focus on comprehensive multidisciplinary assessments and appropriate management of symptoms. There are no controlled studies for the treatment of neuropsychiatric manifestations of HD, but available evidence indicates efficacy for both nonpharmacological and pharmacological treatment modalities. The goal of treatment is to improve the quality of life for both the individual with HD and their caregivers.

is professor and chairman, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, Ohio, and is the section chief for geriatric psychiatry, Cleveland Clinic, Cleveland, Ohio. 

is the manager of Behavioral Health Social Work, Cleveland Clinic Akron General, Akron, Ohio. 

, is an attending psychiatrist, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, Ohio.

Medical, surgical, and genetic treatment of Huntington disease

Huntington disease: pathogenesis and treatment

3. Bates GP, Dorsey R, Gusella JF, et al. 

Huntington’s disease: neuropsychiatric manifestations of Huntington’s disease

Mechanisms of neurodegeneration in Huntington’s disease

Huntington disease: natural history, biomarkers and prospects for therapeutics

7. Teixeira AL, de Souza LC, Rocha NP, et al. 

Revisiting the neuropsychiatry of Huntington’s disease

9. Loi SM, Walterfang M, Velakoulis D, Looi JC. 

Huntington’s disease: managing neuropsychiatric symptoms in Huntington’s disease

10. van Duijn E, Craufurd D, Hubers AAM, et al; European Huntington’s Disease Network Behavioural Phenotype Working Group. 

Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY)

11. Kachian ZR, Cohen-Zimerman S, Bega D, et al. 

Suicidal ideation and behavior in Huntington’s disease: systematic review and recommendations

12. Oosterloo M, Craufurd D, Nijsten H, van Duijn E. 

Obsessive-compulsive and perseverative behaviors in Huntington’s disease

Understanding HD psychosis: an analysis from the ENROLL-HD database

14. Anderson KE, van Duijn E, Craufurd D, et al. 

Clinical management of neuropsychiatric symptoms of Huntington disease: expert-based consensus guidelines on agitation, anxiety, apathy, psychosis and sleep disorders

15. Herzog-Krzywoszanska R, Krzywoszanski L. 

Sleep disorders in Huntington’s disease

16. Martinez-Horta S, Sampedro F, Horta-Barba A, et al. 

Structural brain correlates of dementia in Huntington’s disease

Cholinesterase inhibitors for rarer dementias associated with neurological conditions

Neuropsychiatric manifestations of Huntington disease can present decades before the motor symptoms become apparent, making the role of the psychiatrist all the more important.

Early Warnings: Neuropsychiatric Manifestations of Huntington Disease

Since the 1980s, shareholder-value ideology (boosting profits above all other considerations) has led to a pattern of corporate behavior with troubling consequences. It has created employment instability, undermined productivity and innovation, exacerbated income inequality, and compromised the environment. The erosion of middle-class jobs has created enormous mental stress and uncertainty. Structural changes in employment help account for this, including the fissuring of the workplace, the end of the norm of a career with one company, and offshoring of employment to low-wage nations (driven by globalization and technological change).

Corporations have implemented these practices purely for financial gain, pursuing strategies to maximize returns to shareholders and high-level executives. This has encouraged an excessive focus on short-term returns and a decline in long-term investment. It has not sufficiently taken into account the human cost of such strategies. As an alternative, there are a number of efforts to advance stakeholder capitalism. Stakeholder capitalism would ensure that the broader interests of workers, local communities, and society are represented on corporate boards. The stakeholder value model thus builds a multi-bottom line approach, which goes beyond shareholder value creation to include a broader array of economic and societal values.

The Economic Burden of Brain Health Disorders

 emotional, behavioral, and cognitive health across the lifespan. In this context, compromised brain health greatly increases the risk of disorders (for example, depression, anxiety, substance misuse, dementias, neurodevelopmental disorders, and neurocognitive disorders).

 In total, brain health disorders cost the global economy more than $3 trillion per year in lost productivity.

In particular, mental health has been a growing concern among workers as the pandemic has worn on. According to data from the Society for Human Resource Management (SHRM), roughly 41% of employees feel burnt out, drained, or exhausted from their work.

 In addition, nearly 1 in 4 employees report frequently feeling down, depressed, or hopeless—yet more than 1 in 3 employees reported having done nothing to cope with these feelings.

 Having a significant proportion of the workforce reporting such symptoms is particularly concerning, as depression is associated with acute changes in cognitive capacity that can persist as residual symptoms after pharmacological treatment.

 These changes in cognitive capacity can have a detrimental impact on problem solving, memory recall, and motivation.

 Given the implications of these effects on workforce productivity and overall well-being, mental health should be among companies most pressing concerns.

Looking beyond mood and psychiatric illness, companies should also consider the implications of dementia and Alzheimer disease. According to a study conducted in Spain, the costs related to loss of labor productivity due to informal caregiving for people with dementia amounted to $5370 per individual per year.

 These informal caregivers experienced partial absenteeism and burdens that disabled them from maximizing productivity. Furthermore, research shows that 23% of individuals who will eventually be diagnosed with Alzheimer disease show accelerated cognitive decline around 5 years before an official diagnosis.

 This accelerated cognitive decline can be clinically referred to as mild cognitive impairment, but it is critical to note that the deterioration in brain health is progressive. Prior to mild cognitive impairment, individuals likely experience a period of undiagnosed mild cognitive decline 6 to 7 years prior, though they may be able to remain in the workforce during this time. 

Notably, issues of mental health and cognitive health are often considered separately, although they are inextricably linked. Brain Capital provides a mechanism to consider these in a more integrated way. 

Brain Capital is a novel form of capital that puts a premium on brain health and brain skills.

 Brain skills are critical in a digitized economy and include self-control, emotional intelligence, creativity, compassion, altruism, systems thinking, collective intelligence, and cognitive flexibility. Brain health must be optimized to support the necessary brain skills to thrive.

We refer to a digitized economy that places a premium on cerebral rather than manual skills as a Brain Economy. Brain Capital is clearly critical in an already digitized economy, especially as automation replaces traditional jobs that relied on manual skill.

 In a Brain Economy, innovation is a tangible and increasingly pivotal measure of employee productivity, and innovation is channeled through employee thoughts, ideas, and creativity.

Innovative Approaches to Promoting Brain Capital in the Workplace

Several approaches can promote Brain Capital in the workplace. These range from multiorganization workplace initiatives (

), to novel accounting frameworks, to social impact investing, to venture capital investing, to novel indices for tracking and measuring issues over time.

One example is emotional flexibility training for private sector knowledge workers. In 1 pilot study conducted to explore the effects of such a program, emotional flexibility advancement was found to be a highly effective treatment in clinical settings for depression, anxiety, and chronic pain.

 This approach—which had not previously been empirically explored with private sector, high-paced, high-demanding, and highly educated knowledge workers—demonstrated broad improvements in self-efficacy for those in the treatment group versus the control group. These results suggest that emotional flexibility boosts both well-being and performance.

Human capital can be a company’s greatest asset; it can make or break the business strategy and is a key differentiator. A company’s intangible assets, including human capital and culture, are now estimated to comprise on average 52% of a company’s market value.

 To date, given the intangible nature of strong corporate culture, stakeholder leadership, and employee well-being, companies have struggled to quantify the contribution of their human capital assets. But the principles of the Human Capital Accounting Framework, recently published by the World Economic Forum and Willis Towers Watson, could help firms measure Brain Capital effectively.

 A Human Capital Accounting Framework couldenable a company to monitor and assess the return on its investments in its employees in the same way that it measures returns on financial and intellectual capital.

The Global Reporting Initiative (GRI), in partnership with the Robert Wood Johnson Foundation, has developed health metrics that include social impact in current sustainability indexes.

 Encouraged by the added measure of certainty and transparency surrounding their activities, investors large and small would allocate more capital to financing positive initiatives, and entrepreneurs would devise business models whose ambition and growth potential match investor and market demand. Continued refinement of these taxation and accounting practices that prioritize Brain Capital may support improved workplace and societal well-being.

Venture capital companies have recently made record-breaking investments in mental health, with $637 million invested in more than 60 different mental health companies, almost 23 times the investment observed in 2013.

 Lyra Health was just valued at more than $1 billion, making it the first unicorn in mental health.

 The company, which provides mental health benefits for large employers, offers an array of in-person and remote behavioral therapy that helps remove access barriers to high-quality mental health care. The demand for teletherapy services is soaring, particularly as employers look to support workers during the 

. The company has added more than 800,000 new members since the start of the pandemic.

Novel Indices for Tracking and Investing in Brain Capital

 The central components of Brain Capital need to be formalized and developed into an investment plan. Since one cannot manage what one does not measure, developing a Brain Capital Index (BCI) to track the progress of this approach is critical.

Such an index could help track the Brain Capital impacts of companies and governments. The index could also track the value of investments in this area. If such an index were investable—as is the case for mutual funds or exchange-traded fund—it would encourage investment in the entire space by opening it to the passive investor. Index-tracking funds have recently passed the $10 trillion mark of assets under management globally, surpassing assets under active management for the first time. Attracting even a small fraction of global passive investment using a BCI would transform the Brain Economy as a whole. Consequently, creating a well-defined and easily computed index is a key part of investing in a Brain Economy.

The BCI could be associated with a range of potential components. Health-related metrics could include incidence and prevalence metrics, access to care, and relapse rates. In particular, access to mental health care for child and youth populations is of paramount importance, so coverage for families and employees should be prioritized. As of September 9, 2020, the National Council for Behavioral Health stated on its website that the demand for mental healthcare is at an all-time high; however, the ratio of professionals to patients is incredibly low, suggesting it should be tracked. To improve access, more efforts toward training and incentivizing providers need to be made. A BCI could also track purpose at work, as it has been shown to have a range of brain health benefits, including reducing the likelihood of dementia and stroke.

 Created in partnership between Thrive Global, SAP SuccessFactors, Qualtrics, and Fortune, the Thrive XM Index aims to assess and quantify individual experiences to gauge how employee well-being is directly connected to business outcomes. According to the Thrive Global website, the Index will combine employee-reported experience information, HR-reported performance insights, and business performance data, allowing companies to receive a comprehensive view of the way experience metrics (X-data™) and HR metrics (O-data™) can collectively serve as leading indicators for business performance.

Refining the Return on Investment Analysis

An emphasis on returns on investment (ROI) is critical for tracking and investing in Brain Capital. According to a recent report by Deloitte Canada, a pioneering research initiative determined that positive ROI for workplace mental health initiatives are within reach for Canadian businesses.

 Companies with mental health programs in place for 1 year had a median annual ROI of $1.62 for every dollar invested, and the median annual ROI more than doubled for companies with programs in place for 3 or more years, valued at $2.18 for every dollar spent.

 Components of the research included determining and tracking key performance indicators, assessing the effectiveness of interventions with employees, and regularly calculating ROI. Though often overlooked, these elements are essential to demonstrating the financial and nonfinancial benefits of mental health programs. Robust performance measurement enables organizations to “achieve desired program impact, improve adoption rates, and enhance decision-making.”

 Deloitte’s work helps build a framework for determining the ROI of workplace mental health initiatives. However, for optimal, far-reaching impact, the framework must be expanded to include a wider span of issues that Brain Capital encapsulates, such as brain skill issues and aging brain health conditions.

Recommendations for Building Brain Capital at Work

To propel this field forward in the coming years, clear recommendations are required for all stakeholders. These stakeholders include human resource managers, employee benefit managers, social impact investors, and beyond. Recommendations are outlined in 

Brain and mind issues must play a central role in measuring the sustainability and societal impact of investment in a workforce. A Brain Capital perspective needs to be integrated into existing frameworks, programs, and investment models to prevent or mitigate the profound effects and economic toll brain health disorders have on the workplace and society.

is a pre-medical human biology student at Stanford University.

is an MD candidate at David Geffen School of Medicine at UCLA.

is an associate with the PRODEO Institute and Thiel Fellow at Stanford University.

is head of the OECD New Approaches to Economic Challenges Unit and Senior Advisor to the OECD Secretary General.

is a neuroscientist and senior director at the Milken Institute Center for Strategic Philanthropy.

is the founding director of the Center for Brain Health at UT Dallas.

is a T. Boone Pickens Distinguished Scientist at the Center for BrainHealth, a co- director at Global Brain Health Institute, professor emeritus at Trinity College Dublin, and founding director of its Institute of Neuroscience.

is the global head of Science for Minds at Johnson & Johnson.

is president of the Euro-Mediterranean Economists Association.

is a co-founder of the PRODEO Institute, adjunct associate professor with the Institute for Mental and Physical Health and Clinical Trials (IMPACT) at Deakin University, and an instructor with the Global Brain Health Institute.

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Brain health INnovation diplomacy: a model binding diverse disciplines to manage the promise and perils of technological innovation

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https://www.benefitnews.com/news/its-a-fools-choice-when-employers-ignore-invest-in-mental-health-benefits

4. Perini G, Ramusino MC, Sinforiani E, et al. Cognitive impairment in depression: recent advances and novel treatments. 

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The American Consumer Institute Center for Citizen Research

https://www.theamericanconsumer.org/2016/05/productivity-gdp-alzheimers/

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8. Wilson M, Wilkerson B, Price T, et al. BRAIN Health + BRAIN Skills = BRAIN Capital. 2011. Accessed February 15, 2021. 

http://www.mentalhealthroundtable.ca/report/MHR_FinalReport.pdf

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10. SHRM. SHRM Foundation, One Mind, Psych Hub launch mental health and wellness in the workplace initiative for employers. News release. July 15, 2020. 

https://www.shrm.org/about-shrm/press-room/press-releases/pages/shrm-foundation-one-mind-psych-hub-launch-mental-health-and-wellness-in-the-workplace-initiative-for-employers.aspx

11. PsychHub. Mental health & wellness in the workplace. Accessed February 15, 2021. 

https://psychhub.com/initiatives/mental-health-wellness-in-the-workplace/

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"R U OK?": A meaningful question to foster a culture of caring at EY

http://workplacementalhealth.org/News-Events/News-Listing/R-U-OK-A-Meaningful-Question

14. UsAgainstAlzheimer's. The Global CEO Initiative on Alzheimer Disease (CEOi). Accessed February 15, 2021. 

https://www.usagainstalzheimers.org/our-enterprise/CEOi

Brain health disorders cost the global economy more than $3 trillion per year in lost productivity. What can we do about it?

Cognitive Disorders

PsychQuiz: Cognition in Schizophrenia

Is There a Link Between Exercise, Cognition, and Schizophrenia

Early Warnings: Neuropsychiatric Manifestations of Huntington Disease

Smart Growth: the Case for Measuring Brain Capital

Mini Quiz: Evaluating Dementia

The Troublesome Tale of Cognitive Deficits in Patients at CHR for Psychosis

The Battle of the Sexes in First-Episode Psychosis

A Recipe for Homemade Obesity: The Association Between Depression, Obesity, and Cognitive Deficits

Cognition, Bipolar Disorder, and the Self

Diverse Patients, Common Ground