CEXP 538 Brain Health Fall 2024 Module 9 PDF

CEXP 538 BRAIN HEALTH Fall 2024 Module 9 OUTLINE BRAIN HEALTH INTRODUCTION TYPES ALZHEIMER'S’ DISEASE MULTIPLE SCLEROSIS PARKINSON’S DISEASE BRAIN HEALTH: INTRODUCTION  BRAIN HEALTH Introduction Can be broadly defined as the...

CEXP 538 BRAIN HEALTH Fall 2024 Module 9 OUTLINE BRAIN HEALTH INTRODUCTION TYPES ALZHEIMER'S’ DISEASE MULTIPLE SCLEROSIS PARKINSON’S DISEASE BRAIN HEALTH: INTRODUCTION  BRAIN HEALTH Introduction Can be broadly defined as the optimal or maximal functioning of behavioral and biological measures of the brain and the subjective experiences arising from brain function 2018 Physical Activity Guidelines Scientific Report (1) concluded that there is unequivocal evidence that exercise influences brain health and that individuals with conditions that affect brain health could greatly benefit from engaging in exercise.  BRAIN HEALTH Introduction Attention Deficit/Hyperactivity Disorder Alzheimer’s Disease Anxiety & Depression Autism Spectrum Disorder Concussion Cerebral Palsy Guillain-Barré Syndrome Intellectual Disability & Down Syndrome Multiple Sclerosis Parkinson’s Disease  BRAIN HEALTH Alzheimer’s Disease Irreversible, progressive brain disorder Characterized by early and progressive declines in learning and memory, as well as other cognitive processes https://www.youtube.com/watch?v=hEw1Yq _4PaA&t=248s Genetic variants that cause Alzheimer’s disease Amyloid precursor protein (APP) on chromosome 21 Presenilin 1 (PSEN1) on chromosome 14 Presenilin 2 (PSEN2) on chromosome 1 Research shows that African Americans, American Indians, and Alaska Natives have the highest rates of dementia  BRAIN HEALTH Alzheimer’s Disease Age-related changes include: Shrinking of certain brain regions Inflammation Blood vessel damage The production of unstable molecules called free radicals Decreased energy production within cells Symptoms Memory impairment Mild Cognitive Impairment Stages Mild, moderate, severe  BRAIN HEALTH Alzheimer’s Disease Risk Factors APOE-e4 is the first risk gene identified and remains the gene with the strongest impact on risk for some populations Type II Diabetes Hypertension  BRAIN HEALTH Alzheimer’s Disease Medications Glutamate regulators are prescribed to improve memory, attention, reason, language and the ability to perform simple tasks Memantine (Namenda®) Cholinesterase inhibitor + glutamate regulator Donepezil and memantine (Namzaric®) Orexin receptor antagonist Suvorexant (Belsomra®) Atypical antipsychotics Brexpiprazole (Rexulti®)  BRAIN HEALTH Alzheimer’s Disease Medications Anti-amyloid treatments work by removing beta-amyloid, a protein that accumulates into plaques, from the brain Donanemab (Kisunla™) Lecanemab (Leqembi®) Cholinesterase inhibitors are prescribed to treat symptoms related to memory, thinking, language, judgment and other thought processes. These medications prevent the breakdown of acetylcholine Donepezil (Aricept®): approved to treat all stages of Alzheimer’s disease. Rivastigmine (Exelon®): approved for mild-to-moderate Alzheimer’s as well as mild-to-moderate dementia associated with Parkinson’s disease. Galantamine (Razadyne®): approved for mild-to-moderate stages of Alzheimer’s disease.  BRAIN HEALTH Alzheimer’s Disease Effects of Physical Activity (De la Rosa et al., 2020) Low levels of physical activity are a risk factor associated with Alzheimer's disease. Older adults who exercise are more likely to maintain cognition. Exercise modulates amyloid β turnover, inflammation, synthesis, and release of neurotrophins, and cerebral blood flow. High-intensity exercise Increase the amount of brain-derived neurotrophic factor (BDNF) in the body Delay the onset Reduce the risk Insulin management Enhance neuroplasticity  BRAIN HEALTH Alzheimer’s Disease Exercise testing considerations Clinical judgment is always needed to determine a person’s safety for conducting a test Standard measures of exertion such as the Borg scale may also be invalid in cases of severe Alzheimer’s disease but, in preclinical and early stages, could be considered a valid assessment tool consideration the presence of these comorbidities. Balance, muscle, or coronary contraindications Exercise considerations There is growing evidence that individuals with Alzheimer’s disease can realize benefits of exercise through improved aspects of physiological and brain health; whether an individual can perform exercise activities on their own depends on the severity of the disease. Long, continuous bouts of exercise are more likely to be helpful and safe in preclinical and early stages of the disease and less likely to be feasible during later stages of the disease. Metabolic, cardiovascular, joint, and muscle atrophy comorbidities may restrict the frequency and duration of exercise. Therefore, it may be appropriate to start an exercise regimen with short bouts of 10 min or less. Targeting multiple modes of activity might be the most effective for enhancing balance, flexibility, strength, and endurance. Adequate warm-up and cool-down periods with monitoring of vital signs are critical for minimizing safety concerns.  BRAIN HEALTH Alzheimer’s Disease Exercise considerations In the earliest stages of Alzheimer’s disease, including MCI, individuals are still capable of performing exercise independently and in the community. Ex Rx should always be performed with the consultation of the individual’s physician and/or neuropsychologist. There may be benefits of training and exercising with the caregiver to help provide support, motivation, and monitoring of safety. Inform individuals, as well as caregivers, that a small amount of musculoskeletal pain during or immediately following an exercise bout is a normal consequence of starting an exercise regimen. Exercising in the morning hours might be easiest and most beneficial, as morning is often when an individual is demonstrating the lowest severity of symptoms. Exercise in nursing homes, memory clinics, or senior care facilities, is encouraged as long as there are properly trained staff to monitor individual progress and safety.  BRAIN HEALTH Introduction Anxiety & Depression Mental illness can be defined as a health condition that changes a person's thinking, feelings, or behavior (or all three) and that causes the person distress and difficulty in functioning 2022 National Survey on Drug Use and Health (NSDUH) Any mental illness (AMI) is defined as a mental, behavioral, or emotional disorder. AMI can vary in impact, ranging from no impairment to mild, moderate, and even severe impairment In 2022, there were an estimated 59.3 million adults aged 18 or older in the United States with AMI. This number represented 23.1% of all U.S. adults. The observed prevalence of AMI was higher among females (26.4%) than males (19.7%). Young adults aged 18-25 years had the highest prevalence of AMI (36.2%) compared to adults aged 26-49 years (29.4%) and aged 50 and older (13.9%). The prevalence of AMI was highest among the adults reporting two or more races (35.2%), followed by White adults (24.6%). The prevalence of AMI was lowest among Asian adults (16.8%)  BRAIN HEALTH Anxiety & Depression Mental Health Treatment — AMI NSDUH defines mental health treatment as having received inpatient treatment/counseling or outpatient treatment/counseling, or having used prescription medication to help with mental health. ○ In 2022, among the 59.3 million adults with AMI, 30.0 million (50.6%) received mental health treatment in the past year. ○ More females with AMI (56.9%) received mental health treatment than males with AMI (41.6%). ○ The percentage of young adults aged 18-25 years with AMI who received mental health treatment (49.1%) was slightly lower than adults with AMI aged 26-49 years (50.0%) and aged 50 and older (52.7%). Mortality ○ Number of suicide deaths: 49,476 ○ Suicide deaths per 100,000 population: 14.8 Costs Medical spending to treat adults with mental disorders totaled $106.5 billion in 2019  BRAIN HEALTH Anxiety & Depression (CDC, 2024) Risk factors Genetics Social drivers such as experiencing interpersonal and institutional discrimination Lack of access to housing, healthcare, education Lack of access to employment and economic opportunities Adverse childhood experiences and other types of interpersonal violence Social isolation Poor emotional well-being or coping skills Ongoing or chronic medical conditions, such as a traumatic brain injury, cancer, or diabetes Use of alcohol or drugs Examples of protective factors Access to quality employment, housing, education Strong social connection and stable, positive relationships Positive coping skills Living in safe communities with access to preventive care and mental and physical health services  BRAIN HEALTH Anxiety & Depression  BRAIN HEALTH Anxiety & Depression (CDC, 2024) https://www.youtube.com/watch?v=MEn0XlnxEnM Warning signs marked personality change, inability to cope with problems and daily activities, strange or grandiose ideas, excessive anxieties, prolonged depression and apathy, marked changes in eating or sleeping patterns, thinking or talking about suicide or harming oneself, extreme mood swings—high or low, abuse of alcohol or drugs, and excessive anger, hostility, or violent behavior. National Mental Health Hotline 866-903-3787 National Suicide Prevention Hotline 988  BRAIN HEALTH Anxiety & Depression (CDC, 2024) Medications Antidepressants Anti-anxiety medications Stimulants Antipsychotics Mood stabilizers  BRAIN HEALTH Anxiety & Depression Exercise testing considerations All individuals with anxiety and/or depression should be screened for medication use prior to exercise testing for potential contraindications. In particular, benzodiazepines may cause drowsiness and poor coordination as well as reduce the plasma catecholamine response to exercise Individuals with anxiety disorders have had mildly impaired blood pressure (BP) responses to cardiovascular exercise and should be screened prior to exercise testing. In particular, individuals with generalized anxiety disorder have demonstrated elevated worry and poor vagal tone via heart rate (HR) variability, both of which could negatively impact their exercise testing. Women with anxiety disorders and without coronary artery disease history have an increased ischemia risk during exercise testing  BRAIN HEALTH Anxiety & Depression (CDC, 2024) Exercise considerations The 2018 Physical Activity Guidelines for Americans recommendations is appropriate for reducing anxiety Frequency— the effects of exercise appear to be greatest when sessions occur three to four times per week. Intensity–moderate and vigorous intensity PA (i.e., exercise) reduce anxiety (90). In individuals with primary diagnoses of other medical conditions, light, moderate, and vigorous intensity exercise were all associated with reduced anxiety. There is some evidence that higher intensity aerobic exercise programs ( e.g. , treadmill running at 60%–90% maximum heart rate [HRmax] or 60% V̇O2max or greater) had greater effects for decreasing anxiety than lower intensity ones (e.g., walking below 60% HRmax or V̇O2max) (91). Time–Anxiety reductions are evident following bouts lasting 1–30 min and may increase for bouts lasting 61–90 min. Effects are evident in programs lasting from 4 to 15+ wk; however, effects may taper over time. The largest responses have been found from sessions lasting 30+ min and programs lasting 3–12 wk (86). Type–Both aerobic and resistance exercise training appear to be effective for reducing symptoms of anxiety in healthy and clinical populations. Resistance training may reduce anxiety more in healthy populations than in populations with physical or mental illness. It is not clear whether combining different types of activity leads to greater reductions in anxiety.  BRAIN HEALTH Anxiety & Depression (CDC, 2024) Exercise considerations The effects of aerobic exercise are more profound among individuals who are clinically depressed Frequency–The cumulative frequency of exercise matters more for individuals with depressive disorders than those without. Programs with 12 or fewer days of exercise have inconsistent effects; however, programs lasting 13 or more days consistently reduce depressive symptoms in individual samples. Intensity–There is not enough evidence to indicate that one particular intensity is more effective than another for reducing depressive symptoms. PA at any intensity level appears to be effective for reducing depressive symptoms. Even though more evidence has been collected on moderate-to-vigorous than light PA, it appears that exercise at all intensities is beneficial for reducing depressive symptoms. Time–Exercise has acute or immediate effects on core affective states that can be useful for temporarily alleviating depressive symptoms after exercise. Bouts as brief as 20 min appear to be sufficient to reducing depressive symptoms in individuals without depressive disorders. For individuals with depressive disorders, 45 min is the recommended bout length. Type–The effects of aerobic exercise on depressive symptoms have been characterized better than the effects of flexibility exercises. In general, both aerobic and resistance training reduce depressive symptoms. Mixed programs including both aerobic and resistance training components appear to be more effective than programs with only one form of training; however, this conclusion is based on limited evidence. For individuals with depressive disorders, both aerobic and resistance exercises reduce depressive symptoms. Exercise produces similar effects on depressive mood to stretching, meditation, and relaxation (92).  BRAIN HEALTH Multiple Sclerosis Chronic inflammatory disease, causing sclerotic lesions in multiple areas of the CNS, including the brain, spinal cord, and optic nerve. An inflammatory immune-mediated process damages the myelin sheaths that insulate neuronal axons, the underlying axons, and the myelin-producing oligodendrocytes These changes interrupt or slow the transmission of neural impulses within the CNS, impairing bodily functions that the CNS controls and eventually resulting in a wide array of associated conditions, disability, and shorter than normal lifespan  BRAIN HEALTH Multiple Sclerosis Onset of MS usually occurs between the ages of 20 and 50 yr and affects women at a rate two to three times more than men Disease course of MS is highly variable from individual to individual and within a given individual over time  BRAIN HEALTH Multiple Sclerosis Types Clinically isolated syndrome (CIS) is the first clinical presentation of neurologic symptoms indicative of inflammation and demyelination in the CNS. Some people with CIS may not develop MS, especially if there is no MRI evidence of lesions in the brain. Relapsing–remitting MS (RRMS) is characterized by clearly defined relapses followed by partial or full remissions. During periods of remission, there is no evidence of worsening symptoms. RRMS is the initial diagnosis for about 85% of MS cases. Primary progressive MS (PPMS) is characterized by progressive worsening of neurologic function and disability from the onset of symptoms, without relapses or remissions early in the course. About 15% of individuals with MS are initially diagnosed as following this clinical course. Secondary progressive MS (SPMS) follows the RRMS course, and most people with RRMS transition into this course. SPMS is characterized by a progressive worsening of neurologic function; however, the individual may have periods without progression.  BRAIN HEALTH Multiple Sclerosis Causes Abnormal immune response (inflammation) Environmental factors Geographic location Vitamin D Smoking Obesity Infectious disease Epstein-Barr virus (EBV) Human herpes virus-6 (HHV-6) Canine distemper Chlamydia pneumonia Measles  BRAIN HEALTH Multiple Sclerosis Symptoms blurred or double vision, or total vision loss hearing impairment reduced sense of taste and smell numbness, tingling, or burning in the limbs loss of short-term memory depression or personality changes headaches changes in speech facial pain Bell’s palsy muscle spasms difficulty swallowing dizziness, loss of balance, or vertigo incontinence or constipation weakness and fatigue tremors or seizures erectile dysfunction or lack of sexual desire  BRAIN HEALTH Multiple Sclerosis Diagnosis MRI spinal fluid analysis blood tests evoked potentials (such as an EEG) Prevalence White people (but not Latinx/Hispanic): 374.8 per 100,000 (about 4 people out of 1,000) Black people (but not Hispanic/Latinx): 298.4 per 100,000 (about 3 people out of 1,000) People of “other races” (including Asians, Native Americans, Alaska natives, multi-race individuals and unknown): 197.7 per 100,000 (about 2 people out of 1,000) Hispanic/Latinx people (of any race): 161.2 per 100,000 (about 1 ½ people out of 1,000)  BRAIN HEALTH Multiple Sclerosis Exercise benefits Bladder and bowel function Bone density Cardiovascular fitness Cognitive function Energy levels Flexibility Mood Strength  BRAIN HEALTH Multiple Sclerosis Exercise testing considerations Avoid testing during an acute exacerbation of MS symptoms. Closely monitor for any signs of fatigue, overheating, or general worsening of symptoms as exercise intensity increases. Perform exercise testing earlier in the day because fatigue generally worsens throughout the day in individuals with MS. Conduct exercise testing in a climate-controlled room (72° to 74° F [22.2° to 24.4° C], low humidity) and use electric fans or cold neck packs as appropriate. Furthermore, assess for impaired sensation prior to applying a heat pack. Use RPE in addition to HR to evaluate exercise intensity. Individuals with MS may experience cardiovascular dysfunction as a result of autonomic dysfunction (254). HR responses may be blunted during exercise, and therefore, HR may not be a valid indicator of exercise intensity (255). In most individuals with MS, a cycle ergometer is the recommended method of testing aerobic fitness because this modality requires less balance and coordination compared with walking on a treadmill (256). Individuals with balance and coordination problems may require the use of an upright or recumbent cycle leg ergometer with foot straps. In select individuals, a recumbent stepping ergometer or dual action stationary cycle that allows for the use of upper and lower extremities may be advantageous because it distributes work to all extremities, thus minimizing the potential influence of local muscle fatigue or weakness in one limb on maximal exercise testing. Individuals who are nonambulatory with sufficient upper body function can be assessed using an arm ergometer.  BRAIN HEALTH Multiple Sclerosis Exercise considerations Commonly used disease-modifying medications such as interferon β-1a and glatiramer acetate have common side effects including altered mood, flu-like symptoms, liver failure, and localized irritation at the injection site. Take medication side effects into consideration with exercise testing and scheduling. The individual should be helped to understand the difference between more general centrally mediated MS fatigue and temporary peripheral exercise-related fatigue. Some individuals may restrict their daily fluid intake because of bladder control problems. They should be counseled to increase fluid intake with increased PA levels to prevent dehydration and hyperthermia, secondary to impaired thermoregulation. Many individuals with MS have some level of cognitive deficit that may affect their understanding of testing and training instructions. They may also have short-term memory loss that requires written instructions and frequent verbal cueing and reinforcement. Watch for transient worsening of sensory and motor symptoms, most commonly, visual impairment, associated with exercise and elevation of body temperature. Symptoms can be minimized by using cooling strategies and adjusting exercise time and intensity.  BRAIN HEALTH Introduction Parkinson’s Disease Progressive neurodegenerative disorder associated with aging Primary area of the brain that is impacted in PD is the substantia nigra pars compacta in the midbrain The motor features of PD are the result of degeneration of the dopaminergic nigrostriatal pathway of the midbrain, which results in a reduction in the neurotransmitter dopamine in the striatum  BRAIN HEALTH Introduction Parkinson’s Disease PD is a form of parkinsonism a clinical syndrome including other neurodegenerative parkinsonian disorders multiple systems atrophy progressive supranuclear palsy corticobasal degeneration The cause of PD is unknown aging, genetic susceptibility, and environmental factors Inflammation and mitochondrial dysfunction may also contribute to the disease process  BRAIN HEALTH Introduction Parkinson’s Disease A 2022 Parkinson’s Foundation-backed study reveals that nearly 90,000 people are diagnosed with Parkinson's disease every year in the U.S. 1.2 million people will be diagnosed by 2030 This represents a steep 50% increase from the previously estimated rate of 60,000 diagnoses annually PD incidence estimates increase with age in the 65+ range.(primary risk factor) PD incidence estimates are higher in males as compared to females at all ages. The increase in the incidence of PD aligns with the growth of an aging population. PD incidence rates are higher in certain geographic regions: the “Rust Belt” (parts of the northeastern and midwestern U.S. previously regulated by industrial manufacturing), Southern California, Southeastern Texas, Central Pennsylvania and Florida. Parkinson’s Disease Treatment Complex due to the progressive nature of the disease, the vast range of motor and nonmotor symptoms, and the different side effects associated with therapeutic interventions Primary medical management for PD is typically some type of dopamine replacement therapy drug therapy, surgery, physical rehabilitation, and exercise programming DBS stimulates the brain at high frequencies and thus replaces abnormal high and variable neuronal firing with a consistent pattern Exercise can reduce disease severity and slow down the progression of the signs of the disease improves strength, aerobic capacity, gait performance, and quality of life in individuals with PD Goal of the Ex Rx for individuals with PD slow down the rate at which the signs of the disease progress reduce the signs of the disease reduce comorbidities prevent secondary complications from muscle disuse improve functional ability, independence, and quality of life  BRAIN HEALTH Parkinson’s Disease ACSM exercise testing recommendations: The variability of motor fluctuations may influence testing outcomes and also daily exercise performance Autonomic nervous system dysfunction can occur with these individuals, thereby increasing the risk of developing BP abnormalities, which can be further affected by medications The occurrence of orthostatic hypertension is directly related to the duration and severity of the disease and can also be induced by any of the dopaminergic drugs that are used to manage PD symptoms Tests of balance, gait, general mobility, ROM, flexibility, muscular strength, core stability, and aerobic capacity are recommended individuals with very advanced PD (HY stage ≥4) and those unable to perform a GXT for various reasons, such as inability to stand without falling, severe stooped posture, and deconditioning, may require a radionuclide stress test or stress echocardiograph A gait belt should be worn For individuals with DBS, the signal from the DBS pulse generator interferes with the ECG recording. Therefore, clinicians should consult with a neurologist prior to performing the exercise test in these individuals, and deactivation of the DBS should be done by a trained clinician or neurologist. HR monitoring can be used when DBS is not activated. RPE should be used to monitor physical exertion levels during exercise testing. There have been no known serious adverse effects exacerbated by the interaction of PD medications and exercise. Cognitive impairment is frequently observed in individuals with PD, although not all individuals with PD will experience cognitive deficits. This may present as feeling distracted, forgetful, slower thinking and information processing, and difficulty concentrating or managing complex tasks. It is recommended that all testing instructions be explained slowly, concisely, and repeated as necessary.  BRAIN HEALTH Exercise training considerations Levodopa/carbidopa may produce exercise bradycardia and transient peak dose tachycardia and dyskinesia. Caution should be used in testing and training an individual who has had a recent change in medications because the response may be unpredictable (263). Several nonmotor symptoms may burden exercise performance The outcome of exercise training varies significantly among individuals with PD because of the complexity and progressive nature of the disease Cognitive decline and dementia are common nonmotor symptoms in PD and may burden the training and progression. It is recommended that instructions be explained slowly, clearly, concisely, and repeated as necessary. Exercises should be demonstrated and broken down into a series of short, simple steps. Utilize verbal, visual, and tactile cues while instructing the individual. Fall history should be recorded. Individuals with PD with more than one fall in the previous year are likely to fall again within the next 3 mo. Precautions should be taken to prevent falls whenever possible, such as avoiding narrow and/or uneven walkways, avoiding sharp turns and pivots, and removing any obstacles on the floor. Incorporate and emphasize fall prevention/reduction and education into the exercise program. Instruction on how to break falls should be given and practiced to prevent serious injuries. Free weights vs. machines Flexibility and ROM exercises should include slow static stretches and passive ROM exercises for all major muscle groups and joints, with an emphasis on the upper extremities and trunk functional exercises such as the sit-to-stand, step-ups, turning over, and getting out of bed as tolerated should be incorporated in an exercise program to improve neuromotor control, balance, and maintenance of ADL.  BRAIN HEALTH Exercise training considerations Programs Parkinson’s Wellness Recovery Neuroplasticity principle–the brain's ability to adapt and rewire itself, by incorporating learning strategies and repetition into exercise routines Up, Rock, Twist, Step Supine, Prone, Quadruped, Sitting, Standing Dual-Task training Retropulsion Power Nordic walking The Lee Silverman Voice Training (LSVT) BIG program Rock Steady Boxing Dance for PD Neuromotor training Specific to goal The ability of the body to change direction or orientation The ability to accelerate and decelerate The ability to stop and start Recognition and reaction times Dual Task Cost/Cognitive Footwork REFERENCES Danielson ML, Claussen AH, Bitsko RH, et al. ADHD Prevalence Among U.S. Children and Adolescents in 2022: Diagnosis, Severity, Co-Occurring Disorders, and Treatment. De la Rosa, A., Olaso-Gonzalez, G., Arc-Chagnaud, C., Millan, F., Salvador-Pascual, A., García-Lucerga, C., Blasco-Lafarga, C., Garcia-Dominguez, E., Carretero, A., Correas, A. G., Viña, J., & Gomez-Cabrera, M. C. (2020). Physical exercise in the prevention and treatment of Alzheimer's disease. Journal of sport and health science, 9(5), 394–404. https://doi.org/10.1016/j.jshs.2020.01.004 Dishman, R.K., Heath, G.W., Schmidt, M.D., & Lee, I.M. (2021). Physical activity epidemiology. Human Kinetics, Inc. DiPietro, L., Buchner, D. M., Marquez, D. X., Pate, R. R., Pescatello, L. S., & Whitt-Glover, M. C. (2019). New scientific basis for the 2018 U.S. Physical Activity Guidelines. Journal of sport and health science, 8(3), 197–200. https://doi.org/10.1016/j.jshs.2019.03.007 Hittle M, Culpepper WJ, Langer-Gould A, et al. Population-Based Estimates for the Prevalence of Multiple Sclerosis in the United States by Race, Ethnicity, Age, Sex, and Geographic Region. JAMA Neurol. 2023;80(7):693–701. doi:10.1001/jamaneurol.2023.1135 Liguori, G. (2021). ACSM's Guidelines for Exercise Testing and Prescription (11th Edition). American College of Sports Medicine. Wolters Kluwer. National Institute of Mental Health. (2022). https://www.nimh.nih.gov/health/statistics/mental-illness.