Remembering, Forgetting and Protecting the Aging Brain
Presented by
Stuart Zola, Ph.D.
Emeritus Professor, Psychiatry and Behavioral Sciences Emeritus Co‐Director, Alzheimer’s Disease Research Center Emory University, Atlanta GA Senior Research Career Scientist, Atlanta VA Medical Center
Disclosure Neither Dr. Stuart Zola, the presenting speaker, nor the activity planners of this program are aware of any actual, potential or perceived conflict of interest.
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Participants completing this program should be able to identify: 1. Disorders associated with short-term, working, long-term, and habit based memory. 2. Strategies to protect the aging brain from memory impairments, Alzheimer’s disease and other dementias that have common risk factors. Policies and Procedures 1. Questions are encouraged. However, please try to ask questions related to the topic being discussed. You may ask your question by clicking on “chat.” Your questions will be communicated to the presenter during the breaks. Dr. Zola will be providing registrants with information as to how to reach him by email for questions after the day of the live broadcast.
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Stuart Zola, PhD Emeritus Professor, Psychiatry and Behavioral Sciences Emeritus Co‐Director, Alzheimer’s Disease Research Center Emory University, Atlanta GA Senior Research Career Scientist, Atlanta VA Medical Center Co‐Founder, NeuroTrack Technologies, Inc President and CEO, Quiet Developments, LLC Order of Merlin, International Brotherhood of Magicians
Feels no pain 75% water 3‐4 lbs. Sulci and gyri folds provide more area Soft; boiled tofu
80 billion neurons
Neurons can fire 50 times/sec
100 trillion synapses Hippocampus 60% of brain is white matter fibers Requires 20% of body’s blood and oxygen Neuron cell bodies and glia make up the gray matter
1 Healthy Habits Rule # 1: There is More than One Kind of Memory Healthy Brain
1. Healthy Diet 2. Exercise 3. Sound Sleep 4. Meditation Short‐Term Memory 5. Social Connections Working Memory 6. Intellectual Engagement
Quick Quiz
■ People’s earliest recollections do not date back before ??? years of age.
What is YOUR earliest conscious memory?
2 Short‐Term Memory and Working Memory Many Different Views
Short‐Term Memory Working Memory
Working Memory / Short‐Term Memory 1‐4‐9‐2‐9‐0‐2‐1‐0‐7‐1‐4
A collection of temporary memory capacities
Work spaces where the brain processes newly acquired information
Each work space is specialized in processing specific types of information ‐ visual, auditory, stories ‐ operate in parallel
What can be held actively in mind beginning the moment that information is received. 1 4 9 2 ‐ 9 0 2 1 0 ‐ 7 1 4 Working memory is the bridge between the first few seconds of encoding and the process of storing memory for a longer time.
Digit span test CHUNKING Short‐lasting, limited capacity, 7+2 items.
3 RULE # 2 Amnesia Can Be Pure
Memory impairment can occur in the absence of other cognitive Short‐Term Memory deficits and on the background of Working Memory normal IQ.
RULE # 3 Certain Memory Abilities Can Be Spared
• On the background of profound amnesia, certain kinds of memory abilities can be quite normal and entirely intact.
• Motor skills, habits, can be entirely normal.
• Different brain regions
4 Everything You Need to Know Understanding Dementia
Declarative Memory:
The ability to consciously recollect facts and events from Hippocampus our lives.
Our everyday memories Passage of time
Consolidation Encoding And Retrieval Storage
Depression Alzheimer’s Both
5 Dementia Amnesia:
Over 90 Causes Memory impairment; absence of other cognitive deficits (damage limited to the hippocampus)
❑ Alzheimer’s Disease Dementia: ❑ Lewy‐Body Disease Memory impairment together with other cognitive deficits (damage ❑ Vascular Dementia involves hippocampus plus cortical regions) ❑ Frontotemporal Dementia (Picks, PSG) Alzheimer’s Disease ❑ Parkinson’s Disease Parkinson’s Disease ❑ Huntington’s Disease Huntington’s Disease
Alzheimer’s Disease Alzheimer’s Disease Cognitive Profile
• Age‐related, and thus far an irreversible Early Changes brain disorder. • Memory - Rapid Forgetting • Cognitive impairments are related to the development of • Executive System Function plaques and tangles; abnormal deposits of proteins • Confrontation Naming • Develops gradually and results in memory loss initially (the hippocampus. • Behavior and personality changes, and a decline in thinking Later Changes abilities (cortical regions associated with each of the specific activities). • Course of decline varies from person to person. • Visuospatial • Age is the greatest risk factor; education is a reverse risk factor. • Increased severity in all cognitive domains
6 Neurodegeneration in Alzheimer’s Disease
Healthy Aging Alzheimer’s Disease
7 Impact of Alzheimer’s Disease Alzheimer’s Disease Links?
• No link between aluminum exposure and AD. • Over 4 million people currently • Age is biggest risk factor and there is a dramatic increase in life • No evidence that the use of aspartame is linked to AD or any other dementias. expectancy • No good evidence of increased risk of AD in individuals who were heavy drinkers earlier in life. • The group over 85 ‐ the group with the highest risk of AD ‐ is the fastest growing group in our population. • Blood transfusion: Sweden and Denmark study: authors conclude that "although our findings do not formally exclude the possibility of neurodegenerative diseases being transmissible via • By the year 2050, 14 million Americans will have AD, if no treatments transfusion, they do offer reassurance" that if transmission exists, it must either involve a available.40% will need intensive care latency period of more than 20 years or be extremely rare.
Risk Factors for Alzheimer’s Differences between men and women and race in Alzheimer’s •Age • Almost 2/3 of Americans with Alzheimer’s are women • it is mainly after the age of 60‐65 that proportion of AD patients becomes sizable • Women live longer than men, and older age is a prime risk factor • Genetics and Family History • New evidence suggests higher risk is due to genetic or biological • presence of ApoE4, the gene coding for apolipoprotein • (cholesterol); more likely to develop at younger age variations or even different life experiences • first‐degree relative with AD • Type and amount of education • 40‐65% of AD have 2 copies of APOe4 • Occupational choices • Gender • seem to be more women than men affected • Possible links between APOEe4 and estrogen • could be artifact because life expectancy longer in women • Older African‐Americans and older Hispanics more likely than older •Head Trauma • even brief period of unconsciousness Whites to have Alzheimer’s • Education • Variables such as cardiovascular disease, education, social engagement • dementia is greater among illiterate subjects • education may increase synaptic density
8 At Least 27 Genetic Variations Underlying Alzheimer’s Genes Are Essential But Not The Whole Story
• Genome‐wide association studies (GWAS) and whole exome sequencing (WES) and whole genome sequencing (WGS) Genes and environment interact. • Identified 27 susceptibility genes or loci • Genetically complex disease: each variant has a small effect on There is genetic vulnerability, but not inevitability. disease risk • Amyloid pathway “Having the gene for Alzheimer’s Disease”: • Immune system/inflammation there is an increased risk you’ll develop the disease, rather than • Tau pathology absolute certainty. • Hippocampal synaptic function The disease occurs only when you have a combination of Alzheimer’s‐ prone genes and Alzheimer’s‐inducing experiences. • Microglial and myeloid cell function • Phosphorylation‐dependent ubiqitination
Fight Back the Alzheimer’s Risk Factors Can We change the Course of
• Your Genes Alzheimer’s and Other Dementias? • APOE e4 [creates a protein that moves cholesterol around] • Fight back: cut cholesterol [many with APOE, and no AD]
• Your Family History • First degree relative with AD increases risk [APOE 60%] Cognitive Ability Primarily • Fight back: make healthy changes together Memory Additional Brain • Head Injury in Your Past Regions Two Strategies • Knocked out for 30 min or longer • Fight back: fall prevention, wear seat belts Alzheimer’s Disease 1. Treatments and cures • Diabetes Normal Mild Cognitive • Increases risk [Excess blood sugar harms blood vessels] Impairment -MCI and other Dementia 2. Early detection • Fight back: diet, medications, activity
• Smoking • 59% higher risk for AD [tobacco amps up oxidative stress] Other Cognitive Abilities • Fight back: stop! Neuropathology
• Microbes and Gut Bugs • Viruses can trigger late‐life brain infections
AARP Bulletin, December, 2017 • Unhealthy balance in digestive system leads to inflammation
9 Mild Cognitive Impairment Conversion Rate From MCI to AD
• Three‐year double‐blind study, 769 MCI patients (Thal, et al., 2003, Alzheimer’s Consortium) • Patients can exhibit the neuropathology of Alzheimer’s Disease (AD), but do not yet meet the clinical criteria for AD • Participants randomly assigned to treatment with placebo, vitamin E (2,000 IU/day), or donepezil (10mg/day)
• Some patients have had follow‐up for two years. • Objective evidence of memory impairment • Current annual conversion rate from MCI to AD is 10‐12% per year, or 30‐36% overall, thus far.
• Normal general cognitive function • Predictors of Progression from MCI to AD
• Presence of apolipoprotein e4 is a strong predictor of conversion. • Reduction in the volume of the hippocampus is a very strong predictor of conversion to AD. • Little or no impairment of activities of daily living • New behavioral assays ‐ digital phenotyping
PET Imaging of Amyloid in Alzheimer’s Disease and MCI
Alzheimer’s Disease Neuroimaging Initiative Control
(ADNI) Klunk et al., Ann Neurol, 04
Alzheimer Disease • Structural imaging detects AD at a stage at which the disease process is so far advanced that neurons are already irreversibly lost. • Can we detect imaging changes earlier, during the Mild Cognitive Impairment stage that will alert us to oncoming cognitive decline? MCI Meltzer et al.
10 A4 Is Alzheimer’s Diabetes of the Brain?
• Anti‐Amyloid in Asymptomatic Alzheimer’s study • Unclear exactly how type 2 diabetes makes you vulnerable to Alzheimer’s • Reisa Sperling, Harvard University ADRC • Clue: The two disorders have a similar genealogy of causes: • Amyloid plaque builds in the brain at least 20 years before symptoms appear • Obesity, highblood pressure, high cholesterol, high triglycerides, high‐fat diet, high‐ • Some people with plaque buildup do not develop Alzheimer’s sugar diet • It is a strong indicator that a person is at risk for the disease • Low physical activity • Will solanezumab, a monoclonal antibody, prevent amyloid buildup delay or • High blood sugar and dysfunctional insulin prevent the onset of Alzheimer’s? • 1,000 people in US, canada, and Australia in 3 groups: • All can lead to brain damage • Has amyloid and gets antibodies against it • Destroying neurons • Has amyloid and gets placebo, salt water solutions • Increasing inflammation • No amyloid monitored as a control group • Increasing risk of stroke
How Do We Assess Memory Impairment? Blood Sugar and Cognition
• Scores on memory tests decline as blood sugar control worsens
• The risk of Alzheimer’s tumbles as blood sugar dips (Whitmer, Kaiser Permanente) • Low‐saturated fat, low sugar diet slashed the odds of diabetics getting Alzheimer’s by normalizing insulin (Craft, Univ Washinton) • Brain levels of amyloid dropped by 25% • Diabetics who corrected periodontal problems improved blood sugar control
Rey–Osterrieth_complex_figure
11 VVisual Recall Immediate Recall
Delayed Recall
Draw a Clock‐Face with Hands Pointing to the Time of 1:50
12 Why Clocks? “SET HANDS TO TEN PAST ELEVEN”
Captures the challenge of visuospatial cognition Seeing the images in your head ‐ visual cortex Remembering the hands and the time requested ‐ hippocampus Plan ahead for the drawing and spacing the numbers ‐ prefrontal cortex The clock test taps the network and ability to integrate all the processes
Predicting Cognitive Decline
13 Approaches to Treating, Slowing, or Preventing AD The problem with Current Drugs
Cholinesterase inhibitors Anti-inflammatory drugs Estrogen-replacement therapy Antioxidants Complementary and alternative medicine The “use-it-or-lose-it” approach A vaccine?
NEURON 1 No effective preventive or therapeutic drugs for Acetylcholine Cholinesterase (enzyme) Alzheimer’s NEURON 2 Cholinesterase inhibitors • Therapies currently focus largely on cholinesterase inhibitors • Donepezil (Aricept) NEURON 1 • Galantamine (Razadyne) • Rivastigmine (Exelon) • Suppression of ionotropic glutamatergic signaling re-uptake • Memantine (Namenda) neurotransmitter • Most neglect the underlying clinical and molecular heterogeneity of the disease NEURON 2 • A4 trial incorporating information of underlying pathological mechanisms • Known genetic risks • Selecting patients more likely to respond to therapeutics tested
14 Ginko biloba Interactions The Right Way to Develop Cognitive Reserve
• Ginko biloba commonly used for dementia, and to improve memory and circulation • Estimated use: 11 million Americans • Ginko + caffeine: may cause bilateral subdural hematoma • Ginko + SSRIs: significant improvement in sexual functioning in women and men.
• F. Ayd, Psychiatric Times, December 2000
Brain Training Games ‐ Just a Placebo Effect? Foroughi, Proceedings of the National Academy, 2016 Taxi Drivers: Changes in the Hippocampus • 50 subjects recruited • 25 for a Brain Training and Cognitive Enhancement Study • 25 to Participate in a Study (no mention of brain Training) • MRI study of 16 London taxi drivers vs 50 age‐, hand‐, and gender‐ • Post playing scores matched controls. • Brain Training group showed a 5‐10 pt increase in cognition scores • In taxi drivers, right and left posterior hippocampus larger and • Study group showed no cognitive change anterior hippocampus smaller than in controls. • How long do any real cognitive benefits last? • Significant correlation between duration of taxi driving and increased • The placebo effect ‐ a bright side: size of R posterior hippocampus, and decreased R anterior. • People’s expectations can influence their cognitive performance • Maguire et al, PNAS, 2000
15 Level of Confidence and Accuracy of Memory Accuracy Score: 0 = poor, 7= good
Account # 1
When I first heard about the explosion I was sitting in my freshman dorm room with my roommate and we were watching TV. It came on a newsflash Score Percent and we were both totally shocked. I was really upset and I went upstairs to talk to a friend of mine and then I called my parents. 0‐1 34 2‐3 20 4‐5 30 Account # 2 6‐7 16
I was in my religion class and some people came in and started talking about it. I didn’t know any details except that it had exploded and the schoolteacher’s students were watching which I thought was so sad. Then after my class I went to my room and watched the TV talking about it and got all the details.
Confidence and Accuracy Making Something Memorable
1……………………………………………..5 Just guessing Absolutely certain • Decide what you need to remember Confidence Accuracy • Pay attention (repeat name) 2 0 • Pace yourself (spaced vs massed) 5 0‐2 • Use memory aids (lists, cards) 5 6‐7 • Be consistent (put keys in same place) • Keep your mind busy (active vs passive)
Overall Correlation (N=44) = .29
16 The Best Reminder Psychological Science, 2016
• ”Reminders by Association” – The Memory Palace • Walk though your home, car • When you see the object the rest will come back to you • Ideal reminder • Attention grabbing • Timing – just the right amount of time between when you see the reminder and need to do whatever it’s telling you
What Memory Challenges are Most Beneficial?
Alcohol Alcohol Induced Blackouts
Awoken after a night of drinking and were clueless about what happened or what you did? • When you drink, you’re killing brain cells. T or F ? Drinking and found yourself in a strange location but had no clue as to how you got there?
Blackouts occur when alcohol prevents neurotransmitters from imprinting memories • A lot of alcohol causes a lot of damage from short-term memory to long-term memory. • Moderate alcohol causes little or no damage Two types of blackouts (memory loss): Partial blackout - after you consume a small amount of alcohol. • But strong effects on developing neurons, they die Forgetting what topic you are talking about in the middle of a conversation is common Forget information that you know, like your address or phone number,or the names of people whom you know well. • Fetal alcohol syndrome When reminded, you can remember Complete alcohol blackout - chronic alcohol consumption May physically be able to function and perform mental tasks • Shrunken brains, reduction in numbers of neurons Ability to make decisions and judge your actions is impaired Little or no control over emotions and impulses during this interval of time Behavior can be wildly unpredictable. • Blackouts may last for a few minutes or up to a week after drinking. During this episode, you are unable to retain any memory. FC When others try to fill in the blanks, you are completely unable to recall any information. A HP
17 Alcohol Affects Many Brain Regions
Frontal Lobe Blood Alcohol Concentration
Impairment
Amygdala Cerebellum Hippocampus
Moderate Drinking in Later Years May Damage Does Alcohol Damage Female Brains More? Heart, and In Turn, Brain Solomon, Circulation, 2016 • Correlation of alcohol consumption in 4, 466 people, average age 76 • The more people drank, the greater the subtle changes in heart’s • Alcoholic women (36) have reduced gray and white matter volumes structure and function and their damage is greater than that of alcoholic men (43). • In men, heavy drinking (more than 14 drinks weekly) linked with enlargement of • Hommer, et al Amer J Psychiatry, February 2001 heart walls pumping chamber (left ventricular mass) • Alcoholic men (44) had striking decrease in brain volume, especially in • Among women, moderate drinkers had reductions in heart function frontal cortex, but not alcoholic women (42). Ventricles increased in • Women appear more susceptible than men to the cardiotoxic effects of both compared to controls. alcohol. • Sullivan and Pfefferbaum, Amer J Psychiatry, 2001, • Possible links to cardiovascular disease and increased incidence of Alzheimer’s in women
18 So is Alcohol Consumption Okay or Not? Drugs and Alcohol
• Alcohol’s effect on memory depends on the amount consumed • Hundreds of mind‐altering drugs • Binge drinking more than triples the risk of dementia later in life • Heroin, methadone, alcohol, cocaine, hallucinogens • Risk of dementia 10x greater if passed out twice in one year binging • Most work by interfering with actions of neurotransmitters • Mimic or block • Moderate intake might have protective effects; jury still out • Monoamine neurotransmitters are the stars, regulate mood, attention, sleep and movement • 1‐6 alcoholic drinks a week, 54% lower risk of dementia • Dopamine, serotonin, adrenaline, and noradrenaline • Alcohol in older brains probably more damaging • Parkinson’s, Huntington’s, depression, bipolar disorder, schizophrenia, headache, sleep disorder • Nondrinkers should not start drinking to prevent dementia • Depression ‐ Serotonin re‐uptake inhibitor • What if there were no alcohol? demo • A transporter protein draws it away • Nearby neurons instead of the synapse
Addiction…Prefrontal Cortex
Impulsivity is the inclination to act upon sudden urges or desires without considering potential consequences. Sometimes people describe impulsivity as living in the present moment without regard to the future.
Compulsivity is a behavior that an individual feels driven to perform to relieve anxiety. Once a person performs the compulsive behavior, the anxiety goes away and restores comfort.
Thus, the presence of these behavioral characteristics in addicted persons indicates that changes to the prefrontal cortex have occurred. Unfortunately, these changes also make the discontinuation of drug use more difficult.
Addiction is a process that coordinates the transition from impulsive to compulsive behavior. Impulsivity occurs during the early stages of addiction. During this phase, people impulsively act on powerful urges to experience the pleasure of their addiction.
As addiction progresses a shift begins to occur. At this point, the compulsive aspect of addiction takes hold. When this shift occurs, people are no longer pursuing their addiction solely for pleasure. The compulsions compel them to participate in their addiction to relieve anxious, uncomfortable feelings. At this later compulsive stage, "pleasure" comes in the form of relief from these anxious, uncomfortable feelings. Thus, despite the negative consequences of addiction, the addictive behavior continues in a compulsive manner.
19 The Anti‐pot: Caffeine Coffee
• Enhances transmission at many glutamate and GABA releasing snaps • 500,000+ people in 10 European countries • A mild stimulant and cognitive enhancer • People who drank 3 daily cups live longer
Harvard University: researchers found that the participants who increased their coffee intake by more • Reduced deaths from all causes than one cup a day (on average, an increase of 1.69 cups per day) over a 4-year period had an 11% • Circulatory and digestive diseases lower type 2 diabetes risk over the subsequent 4 years, compared with people who did not change their intake. • Adjusted for diet, smoking Researchers in the U.S. carried out a study that assessed the link between coffee consumption and • 180,000 participants USC study Parkinson's disease risk. The authors of the study concluded that "higher coffee and caffeine intake is associated with a significantly lower incidence of Parkinson's disease” • African American, Native American, Latino, white
Researchers at Beth Israel Deaconess Medical Center (BIDMC) and Harvard School of Public Health, • Same outcome as European study concluded that drinking coffee in moderation protects against heart failure. They defined 'in moderation' as 2 European cups (equivalent to two 8-ounce American servings) per day. • 1 cup, 12% decrease mortality; 3 cups, 18% • Reduced inflammation, lower insulin resistance, antioxidant effects
Annals of Internal Medicine, 2017
Unexpected Allies in Medicine Brain Health: Go Easy on the Wine, Lysergic acid • Delta‐9‐tetrahydrocannabinol (THC) Caffeine, and Chocolate diethylamide (LSD) • Active ingredient in marijuana Binds so tightly to serotonin receptor that you cant • Reduces the release of transmitters glutamate Global Council on Brain Health ‐ 2018 overdose; dose, 1/10,000 of aspirin and GABA to excite or inhibit other neurons Wine ‐ “unclear if there is any beneficial level Side effects occur because drugs typically bind to of consumption foe brain health” more than their intended receptor • THC reduces the communication of many Not addictive, causes no lasting organic damage to neurons non‐selectively Coffee ‐ “Short‐term effects of increased the brain (as far as we now know) attention…but no consensus on beneficial Can cause psychosis, most often in users with an • Medical marijuana effects for brain health” existing tendency to mental illness • Divided views Hallucinogens often produce consciousness‐ altering experiences Dark Chocolate ‐ “Some evidence that high • 2017 NAS,NIH indicate it can relieve consumption of cocoa flavanols can cut Vivid imagery chronic pain but pain is personal and memory loss…but the amount of chocolate Unbounded thoughts you would need to eat to impact the brain subjective; more study needed would be cancelled out by calories and sugar Used for depression consumed”
Aamodt & Wang, Welcome To Your Brain, 2009
20 HEALTH RISKS Cerebrovascular Disease
Hypertension and Alzheimer’s Vascular Dementia
• In 2013, investigators showed that older people with high blood pressure, or • Inadequate blood flow can damage and eventually kill cells anywhere in the hypertension, were more likely to have biomarkers of Alzheimer’s in their body. The brain has one of the body's richest networks of blood vessels and is spinal fluid. especially vulnerable. • What’s the connection? High blood pressure can damage small blood vessels • In vascular dementia, changes in thinking skills sometimes occur suddenly in the brain, affecting parts of the brain responsible for thinking and memory. following strokes that block major brain blood vessels. So can controlling blood pressure through medication also lower Alzheimer’s • Thinking problems also may begin as mild changes that worsen gradually as a risk? result of multiple minor strokes or other conditions that affect smaller blood • “What we found was that if you didn’t have Alzheimer’s and you were taking vessels, leading to cumulative damage. blood pressure medication, you were somewhat less likely to develop • A growing number of experts prefer the term "vascular cognitive impairment dementia. And if you had dementia from Alzheimer’s disease and you took (VCI)" to "vascular dementia" because they feel it better expresses the certain antihypertensives, the disease was less likely to progress,” Constantine Lyketsos, M.D., director of the Memory and Alzheimer’s Treatment Center at Johns Hopkins. concept that vascular thinking changes can range from mild to severe.
21 Vascular Dementia Multi‐Infarct Dementia
• A series of small, short‐lived blockages that affect relatively small patches of brain cells. • After AD, the leading cause of dementia. • The cumulative effect of many small strokes can lead to multi‐infarct • Caused by blockages and breaches in the cerebral arteries leading to dementia. brain damage. • The severity of symptoms depends on both the location and number • About 20% of AD patients may also be suffering from vascular of blockages. dementia. • Stroke specialists suspect that this is the source of most cases of • AD is insidiously gradual; symptoms of vascular dementia can worsen vascular dementia. noticeably from one day to the next.
22 Concussion Seizures Major Depression
A seizure happens because of abnormal electrical activity in the Overview brain. A concussion is a traumatic brain injury that affects brain function. Effects are usually temporary Usually come on suddenly. Include headaches and problems with concentration, memory, and Length and severity can vary. coordination. Less than one in 10 people who have a seizure get epilepsy. Usually caused by a blow to the head.or violently shaking the head Some concussions cause you to lose consciousness, but most do not. Generalized Seizures It's possible to have a concussion and not realize it. These involve your entire brain from the start. Concussions are particularly common in contact sports, Most people usually recover fully after a concussion. Tonic-clonic (grand mal): The most common subtype. Arms and legs get stiff, and you may stop breathing for a bit. Then limbs will jerk and head will move about, as well. Symptoms Absence seizures (petit mal): Loss of awareness briefly. Can be subtle and may not show up immediately. Children get them more often than adults. Symptoms can last for days, weeks or even longer. Typically, they last only a few seconds. Common symptoms are headache, loss of memory and confusion. The amnesia usually involves forgetting the event that caused the concussion.
Second impact syndrome. Rarely, experiencing a second concussion before signs and symptoms of a first concussion have resolved may result in rapid and usually fatal brain swelling.
NEURON 1
serotonin Depression and Alzheimer’s NEURON 2 • The report, published by Butters in the British Journal of Psychiatry (2013), is a meta‐analysis of 23 previous studies that followed nearly NEURON 1 50,000 older adults over a median of five years. • The researchers found that depressed older adults (defined as those over age 50) were more than twice as likely to develop vascular dementia and re-uptake 65 percent more likely to develop Alzheimer’s disease than similarly aged neurotransmitter people who weren’t depressed. • “We can’t say that late‐life depression causes dementia, but we can say it NEURON 2 likely contributes to it,” said Meryl Butters, an associate professor of psychiatry at the University of Pittsburgh School of Medicine and a co‐ author of the paper.
23 Depression Linked to Alzheimer’s Depression and Alzheimer’s Overlap Symptoms
• Previous research has shown that a history of depression is linked to a • Identifying depression in someone with Alzheimer's can be difficult, doubling of the risk that someone will end up with Alzheimer’s disease. since dementia can cause some of the same symptoms. But this is the first analysis to demonstrate an even stronger association • Examples of symptoms common to both depression and dementia with vascular dementia, a condition caused by strokes or other include: interruptions to blood flow in the brain. • Apathy • Loss of interest in activities and hobbies • That does not mean a causal relationship between depression and • Social withdrawal dementia has been established; it hasn’t. Nor is there any solid evidence • Isolation yet that forestalling depression will prevent dementia. • Trouble concentrating • Impaired thinking
Depression: 3 Problems with Memory Aging attenuates antiviral responses 1. clinical aspects (encoding; attention, focusing problems) Older adults more likely to die after Influenza A viral infection than younger adults Older people produce less interferon 2. side‐effects of treatment (encoding, consolidation Reduced induction of antiviral genes problems) Lower response to infection
3. elevated glucocorticoids (hippocampus is “endangered”)
24 THE HABITS OF PEOPLE LEAST LIKELY TO DEVELOP ALZHEIMER’S DISEASE Behavior • Engagement • Activity
Biology •Age • Genetics • Biomarkers
Alzheimer’s Disease: Nun too Soon Overall Findings from Nun Studies: • The Nun Study of Aging and Alzheimer's Disease - 1986 It’s Never Too Late! • David Snowdon, at the University of Minnesota, • 678 School Sisters of Notre Dame (75-107 yrs old) - Similar environmental influences and general lifestyles make the nuns an ideal population to study, Traits in early, mid, and late life have strong relationships • Importance of early language skills – autobiographical essays with the risk of Alzheimer’s Disease • Complexity, vivacity, fluency – 80% vs 10% developed AD as well as mental and cognitive status in old age.
• The Religious Orders Study - 1992, • David Bennett at the Rush University Medical Center • Importance of engagement later in life: • Social, physical, intellectual creates redundancy in CNS
25 Early education is not the only way to build cognitive reserve (Rush Memory and Aging Project) Should I Worry About It? • If you don’t play the violin or speak another language, don’t fret Forgetting: % Complaining of problem • Various factors later in life can buy more years of cognition Names 83 • Purpose in life – derive meaning from life’s experiences Where you put things 60 • Have clear intentions and goals Words 53 Things people tell you 49 Thread of conversation 41 • Those who scored higher on purpose in life were 2.4 times more likely Things you have done 38 to have avoided an Alzheimer’s diagnosis. Frequently dialed telephone numbers 29 • Higher scores also associated with slower rates of cognitive decline (K. Bolla, 199 healthy adults, 39‐89 years old)
Early Detection Matters Alzheimer’s Association 10 Signs Maintain a Sound Memory
• Memory loss that disrupts daily life ~ Eat balanced, low‐fat diet, B6, B12, no • Challenges in planning or solving problems • Difficulty in completing familiar tasks alcohol • Confusion with time or place ~ Exercise (brain needs oxygen) • Trouble understanding visual images and spatial relationships ~ Minimize use of medications (most common • Problems with words in speaking or writing reason for memory loss in adults) • Misplacing things and losing the ability to retrace steps ~ Laugh (depression impairs memory) • Decreased or poor judgement • Withdrawal from work or social activities ~ Use your memory (stay mentally active) • Changes in mood or personality
26 The Right Amount of Stress Eight in 10 Americans Afflicted by Stress 44% US adults frequently feel stressed 35% sometimes feel stressed 17% rarely feel stressed 4% say they never feel stressed
Age ‐ 65+ less likely to feel stressed Employment ‐ having a regular job Parenthood ‐ children under 18 Gender ‐ women more likely to report Lower‐Income ‐ report more stress than middle‐ and upper‐income adults Hasn’t changed much since 2001‐ 2007
STRESS (acute ‐ OK; chronic ‐ NOT OK) Coping with Caregiving
• Cardiovascular system • Adrenaline produces scarring inside vessels • Scarring becomes magnets for clumping molecules ‐ plaques • High blood pressure • Find a support group • Block vessels of your heart • Elevated insulin levels • Develop a routine • Immune system • Cardiovascular disease • Give yourself a break; day care • White blood cells get stripped of power; killed • Impaired immune system • Don’t be afraid to say yes • Reduced antibodies • Sleep disorder to help • Turns on itself ‐ autoimmune disorders (asthma, diabetes) • Stress and depression (2x) • Care for yourself first • Memory and Problem Solving • Don’t go it alone • Cortisol and the hippocampus
27 Mindfulness Matters • Study each word for 1.5 sec:
In the most basic sense, mindfulness is • Garbage being consciously aware of your thoughts • Waste and emotions. • Jon Kabat‐Zin, Umass SOM, helped patients with Tip chronic pain lead healthier better quality lives. For just a few minutes, close your eyes and • Disposal focus your attention on your breathing. Didn’t reduce pain; helped cope better • Broom Do this without judgement, and don’t try to • Trash Be more attentive, aware of our bodies, functions change your breathing (or stop it from • Heap Reduced depression, anxiety, stress changing). Just be aware of your breathing - focus your • Dump Cognitive Behavioral Therapy (CBT) mind on your breath as it goes in and out. • Refuse Self‐awareness is more than just a fad, especially when • Sack it comes to your brain Done? • Recycle Improved memory has been described as • Junk one of the benefits of mindfulness. • Rubbish • Bag Lets see if it works for you. Most people get about 7
Contextual reminders fail to trigger memory Mindfulness versus reconsolidation in aged humans. Source Memory Normal aging is associated with deficits in episodic memory processes. Mindfulness meditation asks participants to relax and concentrate on the current Day 1: Young and older subjects learned a set of objects (Set 1) in Context A moment. Day 2: Subjects learned a different set of objects (Set 2) Meditators focus on their breathing and Mindfulness meditation creates a period of time in which people Context A (reminder context) reserve judgment on any thoughts that may decrease the amount of evaluation they do of new information Context B (no-reminder context) enter their mind. that they encounter. Day 3: Subjects were instructed to recall Set 1 Source Memory - ability to separate Results: information based on where you There are advantages to this. Young/Reminder subjects had more intrusions from set 2 than did Young/No-Reminder encountered it. Can you name two? Reminder context triggered a reactivation of some Set 1 items on Day 2 Source memory is the memory for By contrast, Older/No Reminder subjects made significantly more intrusions than those in the Reminder condition. where a particular piece of information was There also are disadvantages: seen, heard, thought, dreamt, or imagined. Conclusion: contextual reminders are not sufficient to trigger memory updating The more accurate your source memory for in aged humans, unlike in younger individuals. an event, the better able you are to focus only on things that actually happened. How many of you wrote down the word ‘bin”?
28 Do Puzzles Keep You Young? Up Your Creativity Quotient
• 17,000 people 50 and older 1. Seek Inspiration • More puzzles => better performance on 2. Find a Creative Crew attention, reasoning, and memory 3. Make Beautiful Music • Brains functioned 10 yrs younger 4. Take Time to Play • Need clinical controlled trial 5. Embrace Mistakes • Does function actually improve? 6. Cultivate Curiosity
National Geographic Science, December, 2017
Ward Off Cognitive Decline (MCI) ‐ Advice for Seniors Up Your Cognitive Potential JAMA Neurology, 2017 1. One Task at a Time Playing a game, surfing the web, making crafts and visiting with friends 2. Cultivate Small Wins Decreased risk of MCI in 1,900 adults, average age 77 3. Take Breaks On average about 25% less likely to decline Paradoxically, reading books did not demonstrate any protective effect against MCI, 4. Exercise But especially if in a book club, do not curtail your activity. 5. Quiet Your Space
29 If You Want to Avoid Dementia, Get Hitched! Guard Your Memory • Modifiable risk factors: diet, exercise, alcohol, smoking, and… • Marital status • Physical Activity • Brain Games • 800,000 participants, Asia, NA, SA, Europe • Eat Mediterranean • • Lifelong singletons 42% more likely to develop dementia Aluminum
• Widowed 20% more likely; divorce had no impact (small n) • Friends and Family • Vitamins • Caution ‐ only an observational study; no cause/effect • More social interaction ‐ cognitive dexterity • Managing Blood Pressure • Supplements • Healthier lifestyle decisions as a couple • Sleep • Ginseng and Ginko • Singletons might have difficulties in flexibility of thought (changing)
J. Neurology, Neurosurg, Psychiat, December, 2017 AARP Bulletin, December, 2017
Modifiable Risk Factors Modifiable Risk Factors (cont)
• Some risk factors can be changed to reduce risk of cognitive decline • Social and cognitive engagement • Regular physical activity • Remaining socially and mentally active throughout life may support brain health • Management of cardiovascular risk factors and possibly reduce risk of Alzheimer’s • Diabetes • Exact mechanism by which this might occur is unknown • Obesity • Traumatic brain injury (TBI) • Smoking • Hypertension • Disruption of normal brain activity by jolt or blow to the head • Falls and motor vehicle accidents are leading causes • Healthy diet and lifelong learning/cognitive training may reduce risk • Compared with no TBI, moderate TBI (less than 24 hrs loss of consciousness) is • Education could build a “cognitive reserve” associated with 2x risk for AD; severe (24hrs+) TBI, 4.5x risk for AD • Allows the brain to compensate for the early changes in Alzheimer’s • Decrease risk by wearing seat belts, wearing helmets, no blows‐to‐head‐sports
30 MEMORY MASTER Dressmakers’ Super Power: Vision NELSON DELLIS
• Brain’s ability to translate 2‐D information into 3‐D data • Needed to navigate the world
• Seamstresses 80% more accurate at judging distances “You want to turn information you are trying to memorize into something that your brain naturally prefers to absorb” ‐ typically an image.
“Once you have that picture, the next step is to store it somewhere in your mind where you can safely store it and retrieve it later.”
National Geographic Science, December, 2017
The Right Ways to Protect the Brain from They’re All Out There… Metabolic Syndrome
• Loss of cholinergic neurons • Hippocampal dysfunction via biology, or head trauma • Amyloid plaques and neurofibrillary tangles • Inflammation • Neurovascular damage • Genetic predispositions or vulnerability • Environmental factors, toxins
31 Anti-inflammatary DIets Whole Grains Boost Longevity Mediterranean diet • Three or more servings per day – Rich in good fats • Oats Multicolored fruits • Quinoa • Brown rice Vegetables • 20% lowered risk of dying early Protein from Fish • 25% lower risk of death from heart disease Improvement in Lipid Sensitivity • 14% lower risk of death from cancer Lower risk of Metabolic Syndrome • Whole grains contain the entire grain kernel • Fiber, iron, several B vitamins – improves cholesterol level
Development of Alzheimer’s The 5% Solution Possibly Linked to Infection
• Great Pyramid of Giza, over 203 huge steps to reach the 454‐foot summit. • Eiffel Tower? 1,665 steps and it's 984 feet tall. Beta amyloid accumulates in the brain as plaque, destroying synapses • Dubai's Burj Khalifa, the world's tallest building, scrapes the sky; it's 2,722 feet tall with 2,909 stairs. • Luckily, you don't have to take that many steps all at once to gain the great health benefits of losing weight. Rudy Tanzi, Harvard University: Amyloid protein might be a defense against • If you're overweight or obese, shedding just 5 percent of your body weight (that's 9 pounds for someone who's 180 pounds) can help reduce multiple risk factors for Type 2 diabetes and coronary heart disease. pathogens that sneak across the aging blood‐brain barrier • Recently, researchers compared the health improvements of 40 obese men and women who lost 5 percent of their body weight with those who shed 10 percent and 15 percent. The 19 people who shed 5 percent saw almost as much improvement in the function of their beta cells (that's where insulin is produced) and in insulin sensitivity as those who lost 10 and 15 percent. Injected bacteria into mice brains, and beta amyloid surrounded bacteria, • That's great news for folks who think they have to go from severely overweight to thin to see health improvements. trapping the bacteria, but then left behind plaques. • Just aim for 5 percent at a time by making simple lifestyle changes: start a walking routine pronto. Mice that could not produce beta amyloid died. Could we stop the bacteria from getting in?
Or reduce the bacteria?
32 Chronic Inflammation That Fire in Your Brain Promotes Dementia
• Low‐level inflammation can persist in your brain, destroying neurons and making you vulnerable to memory loss and Alzheimer’s • A normal immune system response gone awry: microglia view amyloid as an invader, overreact and kill millions of healthy brain cells • Blood test measures inflammatory agents, such a c‐reactive protein • High blood concentrations associated with high risk of dementia • No question that inflammation is a prime enemy of the aging brain
Take Care of Your Teeth Reducing Inflammation • People with tooth and gum disease are apt to score lower on memory The Immune system response and cognition tests (Crout, UWV) Release of leukocytes (white blood cells) • Infection in gum disease gives off inflammatory by‐products that travel to areas of Fight off invaders, remove damaged cells, facilitate tissue repair the brain involved in memory function Sometimes this adaptive immune process can become pathological in its own right • Brushing flossing and generally preventing gum problems may keep your Auto‐immune diseases memory sharper Rheumatoid arthritis Inflammatory bowel disease • Having periodontal disease (loose and missing teeth) before age 35, Psychiatric conditions, depression quadrupled the likelihood of dementia later in life ‐ ‐ inflammation Depression ‐> obesity, cardiovascular disease, and other issues linked to depression • Elderly individuals with the most severe gingivitis – inflamed gums – are But inflammation is not causing the two to three times more likely to show impaired cognition depression, although the two are linked
33 THREE NATURAL WAYS OF FIGHTING INFLAMMATION The Dietary Inflammatory Index
•Curcumin The Dietary Inflammatory Index (DII) is used to assess the Curcumin is a powerful antioxidant that is the main chemical in inflammatory potential of nutrients and foods in the context Turmeric. Curcumin reduces inflammation by blocking of a dietary pattern. inflammatory cytokines and enzymes. Also, Curcumin improves Diet research is tricky. Turmeric may work anti-inflammatory the body's immune response. wonders for mice, but “that's in the context of rodent chow with a whole different set of macro and micro nutrients,” • Omega-3 fatty acids explains Martha Clare Morris, a nutritional epidemiologist at Omega-2 fatty acids commonly available in fish oils, function as Chicago's Rush University. And context matters. The typical anti-inflammatory substances and well-prescribed doses of the Mediterranean diet calls for loads of seafood a week, and yet omega-3 fatty acids help reduce inflammation. studies of people taking fish oils as a supplement have not found much benefit. The virtues of fish may lie elsewhere or • Probiotics have more to do with displacing meat. Probiotics are live but helpful bacteria and yeast that have good health benefits, especially for the digestion system, and they also That's why researchers such as Morris prefer to study overall help in reducing inflammation. dietary patterns rather than particular ingredients. Her current project examines whether cognitive decline can be slowed with a regimen called the MIND diet, which combines elements of the Mediterranean diet with another well-studied diet called DASH. It will look at inflammation, but results won't be out before 2021.
Steroids and Non‐steroidal Anti‐Inflammatory Aspirin, steroid and non‐steroidal anti‐inflammatory drugs use Drugs in Alzheimer’s Show Mixed Promise for treating Alzheimer's disease ‐2012 NO‐GO • Several epidemiological studies suggest that long‐term use of non‐steroidal anti‐inflammatory drugs (NSAIDs) may protect subjects carrying one or more ε4 allele of the apolipoprotein E (APOE ε4) against the onset of Alzheimer's • Aspirin, steroid and non‐steroidal anti‐inflammatory drugs (NSAIDs) disease (AD). (traditional and the selective cyclooxygenase‐2 (COX‐2) inhibitors) • The biological mechanism of this protection is not completely understood and showed no significant benefit in the treatment of Alzheimer's disease. may involve the anti‐inflammatory properties of NSAIDs or their ability of interfering with the β‐amyloid (Aβ) cascade. • Therefore, the use of these drugs cannot be recommended for the • Unfortunately, long‐term, placebo‐controlled clinical trials with both non‐ treatment of Alzheimer's disease. selective and selective inhibitors in mild‐to‐moderate AD patients produced negative results. • A secondary prevention study with a selective inhibitor, in patients with mild cognitive impairment was also negative.
34 Supplements-Anti-inflammatories Supplements-Anti-inflammatories Flavonoids Flavonoids Means “Yellow” in Latin CATECHINS Green tea, cocoa, lentil Once called “Vitamin P” for plants FLAVANONES Lemons, grapefruit, oranges May be more effective in cardiovascular FLAVANOLS disease Leafy vegetables, apples, onions ANTHOCYANINS Red Grapes, Berries
Supplements-Anti-inflammatories
Polyphenols
❖ Plant products originally used in tanning
❖ In some kinds of wood, high levels helps prevent rot
❖ Pre-clinical and clinical studies now being performed
35 Supplements-Anti-inflammatories Resveratrol
Polyphenols • Member of a group of plant compounds called polyphenols. • Thought to have antioxidant properties, protecting the body against the kind of damage linked to increased risk for conditions such as cancer and heart disease. Found in the skin of red grapes, but other sources include Curcumin (Turmeric) peanuts and berries. Wine! • Alzheimer's disease. Resveratrol may protect nerve cells from damage and the Resveratrol (Stilbinoid) buildup of plaque that can lead to Alzheimer's. • Diabetes . Resveratrol helps prevent insulin resistance, a condition in which the body becomes less sensitive to the effects of the blood sugar‐lowering Garlic hormone, insulin. Insulin resistance is a precursor to diabetes. • Activates the SIRT1 gene, a biological mechanism that seems to protect the Dark Chocolate body against the harmful effects of obesity and the diseases of aging. Ginger
Supplements Anti-inflammatories Statins Omega-3 Fatty Acids
EPA, DHA and ALA are three primary Omega-3’s Maintain efficiency of cell membranes EPA and DHA from fish, ALA from nuts and seeds Lowers triglycerides May act as an anti-inflammatory Western diets tend to be low in Omega-3 but hig The most prescribed drug in Omega-6
36 Statins and the Brain Statins Possibly Linked to Cognitive Decline
• Fat and the Brain • Cholesterol‐lowering statins are the most widely prescribed • It is not crazy to connect cholesterol‐modifying drugs with cognition; after all, medications in the world, and they are credited with saving the lives one quarter of the body’s cholesterol is found in the brain. of many heart disease patients. • Cholesterol is a waxy substance that, among other things, provides structure to the body’s cell membranes. • But a growing number of users have voiced concerns that the drugs • High levels of cholesterol in the blood create a risk for heart disease, because the elicit unexpected cognitive side effects, such as memory loss, fuzzy molecules that transport cholesterol can damage arteries and cause blockages. thinking and learning difficulties. • In the brain, however, cholesterol plays a crucial role in the formation of • Experts are starting to believe that a small percentage of the neuronal connections—the vital links that underlie memory and learning. population is at risk, and they are calling for increased public • Quick thinking and rapid reaction times depend on cholesterol, too, because the waxy molecules are the building blocks of the sheaths that insulate neurons and awareness of the possible cognitive side effects of statins speed up electrical transmissions. • —symptoms that may be misdiagnosed as dementia in the aging patients who take them.
Statins Possibly Prevent Cognitive Decline The Statin Story as of 2016
• Experimental animal and laboratory studies have suggested that • Now, a team of investigatorsfrom Queens University, Belfast, has used standard Cochrane methodology to evaluate the efficacy and safety of statins for the prevention of dementia in people at risk for dementia owing to cholesterol metabolism in the brain is important in the causal pathway their age. for dementia, possibly by modifying amyloid metabolism. • There is good evidence that statins given in late life to people at risk of vascular • A few studies have shown a possible relationship between mid‐life blood disease do not prevent cognitive decline or dementia. cholesterol levels and risk of dementia, including AD. • Biologically, it seems feasible that statins could prevent dementia due to their role in • Case‐control studies report that patients with AD were less likely to use cholesterol reduction and initial evidence from observational studies was very lipid‐lowering drugs, especially statins. promising. • Longitudinal epidemiology studies have not demonstrated a decreased • However, there were limitations in the earlierstudies involving the cognitive risk of AD among statin users versus nonusers. assessments used and the inclusion of participants at moderate to high vascular risk only. • Two clinical trials of statin therapy to reduce cardiovascular disease have not shown any reduction in risk of cognitive decline or dementia. • Final caution: statins create the greatest problems for drug interactions
37 Healthy Diet Makes Brighter Brains Diet and Cognitive Decline Smythe, Neurology, 2016 Isaacson, Medscape Neurology, 2016
• 27, 860 over‐55s, 40 countries, 5 years • Two different types of nutritional categories that have gained attention • Type of dietary pattern that one follows – the Mediterranean diet, MIND diet • None had diabetes, history of heart disease or stroke • Caloric restriction • Proportion registering a decline in cognitive scores was lower in the people • Nutrients have exploded reporting the healthiest diets (14%) vs unhealthy diets (18%). • Omega‐3 fatty acids, E vitamins, curcumin, caffeinated foods • Higher diet quality is associated with a reduced risk of cognitive decline • Caution: Not all omega‐3’s are created equal • DHA and EPA have most evidence for reducing cognitive decline • Dietary intake may modify the risk of cognitive decline through multiple • People with certain genes may respond differently mechanisms • APOEe4 may respond favorably • Decreasing the risk of stroke • People without that gene may respond less • • Sufficiency of nutrients necessary for neuronal regeneration (group B vitamins) For people with Alzheimer’s disease, no good evidence of effect • Blueberries (flavonols) – ½ cup 3x wk – delayed onset of cognitive decline
Glycemic Index The MIND Diet
• One way to choose fruits and other high‐carbohydrate foods is to check the glycemic index (GI). • MIND stands for Mediterranean‐DASH Intervention for Neurodegenerative Delay. It’s similar to two The GI is a ranking of foods on a scale from 1 to 100, with their score indicating how quickly other healthy meal plans: the DASH diet and the Mediterranean diet. they raise blood sugar levels. • High GI foods are absorbed faster than medium or low GI foods. Low GI foods are best for • You eat things from these 10 food groups: Green leafy vegetables (like spinach and salad greens): At helping control blood sugar levels. least six servings a week; Other vegetables: At least one a day; Nuts: Five servings a week; Berries: • It may be a surprise to learn that most fruits have a low glycemic index. Starchy vegetables like Two or more servings a week; Beans: At least three servings a week; Whole grains: Three or more potatoes and grains are more rapidly digested and have a higher GI index. servings a day; Fish: Once a week; Poultry (like chicken or turkey): Two times a week; Olive oil: Use • Low GI fruits (GI less than 55) it as your main cooking oil; Wine: One glass a day • Apples • You avoid: Red meat, Butter and margarine, Cheese, Pastries and sweets, Fried or fast food • Avocados • One study showed that people who stuck to the MIND diet lowered their risk of Alzheimer’s disease • High‐GI fruits (GI Index of 70 or greater) by 54%. But maybe even more importantly, researchers found that adults who followed the diet • Dates only part of the time still cut their risk of the disease by about 35%. • Watermelon
38 Curcumin Tumeric
• Curcumin is the active ingredient of turmeric, the main spice in curry, and is also Help or Hype? found in limited amounts in Ginger. It is a potent anti‐inflammatory and cancer A relative of ginger, this vivid yellow- preventative molecule, and similar to Fish Oil it seems to be an effective orange spice is common in Indian, metabolic syndrome band‐aid. Black Pepper greatly enhances absorption. Southeast Asian, and Middle Eastern • CAUTION: Limited in vitro evidence suggests that curcumin may cause DNA cooking. It's also been used as medicine damage and suppress the immune system at high concentrations. How these in places like India for centuries to treat findings translate to actual impact on human health is unknown at this time issues such as breathing problems. Lately, turmeric has been touted as a super food that can fight cancer, ease depression, and more.
CURCUMIN Tumeric
Depression Alzheimer's Several compounds in turmeric Disease may support your health. The most People with Alzheimer's have well-known of these is curcumin. chronic inflammation, and turmeric Scientists are excited about seems to have natural anti- curcumin's potential to ease inflammatory effects. So does depression and help turmeric fight Alzheimer's? Sorry, antidepressants work better. But there's no strong scientific evidence so far, research results have been yet that taking turmeric is an mixed. effective way to prevent the disease.
39 The Right Dose of Physical Activity TURMERIC CURCUMIN
Type 2 Diabetes + Viral Infections + PMS ++ High Cholesterol + Arthritis + Headaches + IRB + Cancer +
Motivation – What’s the Dope on dopamine? How many Calories do we Burn? John Salamone, Ph.D., Behavioral Neuroscience Division at the University of Connecticut
• Motivation is regulated by a part of the brain known as the nucleus • Getting out of our chairs can help us better regulate blood sugar and accumbens, according to the latest studies. lessen the risk for diabetes and chronic diseases • This small region, and the neurotransmitters that filter in and out of it, strongly influence whether or not you do things like go to the gym, eat healthfully, or • What about calories? lose weight, experts say. • A key neurotransmitter in this process is dopamine. When it's released in the • Four groups, 74 volunteers, mid‐20s, normal weight nucleus accumbens, dopamine triggers motivation so that you're primed to do • Sit and type for 15 min, then stand up for 15 but don’t move around whatever it takes to achieve an objective, no matter what hurdles stand in • your way, Sit and watch TV for 15 min, then walked on treadmill for 15 min at gentle pace • Stand for 15 min, then sit for 15 min • Dopamine helps bridge what scientists call psychological distance. • Say you're sitting at home on your couch in your pajamas, thinking you really should • Walked on treadmill for 15 min, then sat for 15 min exercise, for example. Dopamine is what enables you to make the decision to be active." • Siting – 20 cal, Standing – 22 cal, Walking – 3x as many calories!!
40 Why Does Exercise Matter? Want to Remember? Go for a Run in 4 Hrs Fernandez, Current Biology, 2016
• The brain’s appetite for energy is enormous • Working out four hours after studying 90 images increased the • 2% of body’s weight, but uses 20% of body’s energy accuracy of recall of the images • The energy supply is glucose, a type of sugar • Watched 3 hrs of nature documentaries during the delay • Absorbed into bloodstream and small intestines • 35 minute interval training; “comfortably hard” effort (80% max heart rate) • Nutrients travel to all parts of the body, into cells • Exercising immediately after provided no boost at all • Cellular process generates a lot of toxic waste ‐ free radicals • Boost most likely affected memory consolidation, i.e., the • Wreck the innards of cells hippocampus and it neurotransmitters • Cause mutations in your DNA • When blood can’t deliver enough oxygen, toxic electrons overaccumilate • More access to blood is better ‐ that’s where exercise comes in • Provides greater access to oxygen and food
Brain Rules, John Medina, 2014
Effect of Exercise on the Aging Brain Direct Effects of Exercise on Brain & Memory in Aged Individuals
Exercise improves cognition and hippocampal One hour, three times per week for plasticity in APOE e4 transgenic mice. three months: Nicol et al., Alzheimer’s and Dementia, 2009 Increased Cerebral Blood Flow
Enhanced Memory
Lowered Blood Pressure
Increased Neurogenesis
41 Can Lifestyle Changes Really Not just exercise, but any activity can do it Reduce Cognitive Decline?
[1] from the National Institute for (Aaron Buchman, Rush) • Between 2009 and 2011, the team of investigators • Actigraph units on the wrists of 1000 participants Health and Welfare, Helsinki, Finland, screened 2654 individuals and randomly assigned 1260 to an • Captured formal exercise and any activity like playing cards, cooking intervention group (n = 631) or control group (n = 629). • Those in the bottom 10% of activity – the people who moved the least – were • A 2‐year, multidomain intervention comprised diet, exercise, cognitive more than 2x as likely to later be diagnosed with Alzheimer’s training, and vascular risk monitoring, while the control group received • Keep moving! general health advice. • The primary outcome was a change in cognition, as measured by a
• Life space – the subject’s range during the previous week (Bryan James, Rush) comprehensive, neuropsychological test battery and again at 2‐year • Left bedroom, porch, yard, neighborhood? follow‐up. • The most constricted to their homes were 2x as likely to develop Alzheimer’s • Those showed that the intervention group had small but significantly better neuropsychological outcomes than the controls.
The Right Dose of Sleep How many hours of sleep are you getting each night? Fewer than 7 ‐ short sleep duration ‐ SSD Health problems far beyond fatigue Linked to elevated risk for cardiovascular disease, diabetes, depression and anxiety Suppression of immune system Less efficient at work; less creative Driving crashes and injuries at work Alters hormone levels, weight gain Optimal sleep period for most adults, 7‐9 hrs Defend that precious time! But not during this workshop!
42 You Call This Rest? Sleep: How Much is Enough?
• Paradox • We don’t know • Sleep is a powerful restorative • Age • Gender • The brain is unbelievably active • Pregnancy • Rapid eye movement (REM) sleep • Puberty • Non‐REM sleep ‐ energy consumed is less than waking state • How much sleep don’t you need? • Sleep loss ‐ brain drain • Battle • Impairs thinking in almost every way • Homeostatic sleep drive (“process S”) • Biological drive for afternoon nap is universal • Circadian arousal system (“process C”) • “Sleep on it” ‐ do better problem solving
Brain Rules, John Medina, 2014
Power Napping Smart Tablets and Smart Phones at Bedtime = Not Good Sleep ~ Napping is a basic right, not a luxury • Blue light delays sleep (especially if sleep 6 or fewer hours a night) • Cells in retina finely tuned to tell the brain to cut melatonin when they are hit by short wavelengths like morning light ~ Duration: 20 minutes of sleep (otherwise not rejuvenated; • Most phones and tablets emit blue wavelength like that “sleep drunkeness”) • iPhones and iPads provide n option for yellowed light at nighttime • Sleep lab subjects who read from an iPad before bed for 5 nights ~ Enhance cognitive performance, reaction time, and mood • Nighttime melatonin levels plummet 55% • Took longer to fall asleep ~ More powerful than caffeine, and no negative side effects • Had less REM • More groggy in morning ~ Don’t need to lie down; can sit at desk
43 Supplements Poor Sleep May be Linked to Alzheimer’s
• Lack of sleep or waking up several times during the night may be bad Melatonin for the brain and may increase the risk of Alzheimer’s disease • Researchers at the Johns Hopkins Bloomberg School of Public Health in Baltimore found that getting less sleep or sleeping poorly was tied Enhances sleep architecture to an increase in brain levels of beta‐amyloid • 70 older adults, average age 76; those who said they got the least Resets circadian rhythm sleep, under five hours a night, or who slept fitfully had higher levels of beta‐amyloid in the brain than those who slept over seven hours a Best dose? night
Sleep and Alzheimer’s Sleep in the Elderly
• One reason why poor sleep may be linked to Alzheimer’s is that sleep • Earlier studies have shown that poor sleep can lead to memory and may help to clear toxic molecules from the brain. thinking problems, even in healthy people. • Studies in mice found that when mice slept, the cells in their brains • People with a common breathing disorder called sleep apnea, which causes literally shrank, making more room for the flow of fluids through the sleepers to awaken briefly hundreds of times during the night, has also been brain. linked to memory problems and an increased risk of dementia. • This increased flow of fluid acted something like the jet sprays in a • But poor sleep, as well as sleep apnea, is a common problem in the dishwasher, flushing away harmful waste products like beta‐amyloid. elderly. • Sound sleep seemed to blunt the effects of APOE‐E4, a gene that • Just because you don’t sleep well doesn’t mean you will get Alzheimer’s disease. predisposes to the development of Alzheimer’s disease. • A sound night’s sleep, though, may be a critical component of a healthy lifestyle – • Those who carried the APOE‐E4 gene, those who slept most soundly showed and might even help to keep Alzheimer’s at bay. the greatest preservation of memory and thinking skills.
44 Sleep Related “Sundowning” in Alzheimer’s Non‐drug Treatments for Sleep Changes
• Daytime napping and other shifts in the sleep‐wake cycle. • Maintain regular times for meals and for going to bed and getting up • Individuals may feel very drowsy during the day and then be unable to sleep • Seek morning sunlight exposure at night. • Encourage regular daily exercise, but no later than four hours before bedtime • They may become restless or agitated in the late afternoon or early evening, • Avoid alcohol, caffeine and nicotine an experience often called “sundowning.” • Treat any pain • Experts estimate that in late stages of Alzheimer’s, individuals spend • Make sure the bedroom temperature is comfortable about 40 percent of their time in bed at night awake and a significant • Provide nightlights and security objects part of their daytime sleeping. • If the person awakens, discourage staying in bed while awake; use the bed • In extreme cases, people may have a complete reversal of the usual daytime only for sleep wakefulness‐nighttime sleep pattern. • Discourage watching television during periods of wakefulness
Supplements The Right Nutrients
Americans spend over $30 Billion dollars on supplements annually
Hundreds of supplements have been identified to improve cognition and health in one form or another.
However, there is little evidence that supplements have significant enhancing effects.
45 Supplements Supplements For your eyes!
❖ Lutein Dietary Fiber ❖ Zeaxanthin Reduce absorbtion of glucose in gut (i.e. may improve insulin resistance) ❖ Both are Carotinoids ❖ Together may help with preventing free Leafy green vegetables, spinach radicals due to exposure to blue light
❖
Glycemic Index The Right Forms of Social Engagement
◇ A measure of how quickly and how much food intake raises glucose levels in blood
◇ Foods that have a high GI include refined grain products, sugary drinks and foods, potatoes
◇ Foods with low GI effects include legumes, fat-free dairy products, some fruits.
46 Staying Involved Socially Social Networks
• Promotes wellness and longevity • Those with larger social networks are better able to postpone some of the worst symptoms and how quickly Alzheimer’s encroaches • 7,000 Californians monitored for 17 years: those lacking social • Not Facebook, not Twitter connections were 2‐3 times more likely to die prematurely. • Close relatives and friends with whom you can discuss private matters • 1,400 people with heart disease: those with a spouse or other confidant, 1/3 less deaths. • People with larger social networks might have better developed people skills – and so a greater reserve of social • 21,000 older adults: attend weekly church associated with 7 years cognition – to fall back on. longer life for white Americans, 14 years for African‐Americans. • Healthwise, August, 2000, UCSD Press • Frequent but unsatisfactory interactions with your children can increase dementia risk (Laura Fratiglioni, Sweden’s Karolinska Institute) • Insanity is hereditary – you get it from your children (Sam Levinson)
Making Aging Positive Successful Aging “Pristine” Aging: • Between 1900 and 2000, average life expectancy increased by 30 years Changes in Cognition are Mild or None • Adults 60 and over are now the fastest growing segment in our population • We’ve created a new stage of life, but have mot yet envisioned its purpose. • We are wired to feel needed, respected, and purposeful • Empowered vs disempowered nursing home residents • Significant improvement in physical and mental well‐being; 50% less mortality • Key is feeling that you are leaving the world better than you found it.
Edna Parker Jeanne Calment Tomoji Tanabe Maria de Jesus 1893‐2008 1875‐1997 1895‐2009 1893‐2009 Age 115 Age 122 Age 112 Age 115
47 You’re Never Too Old
Successful Aging Mary Baker Eddy ‐ Established the Christian Science Monitor newspaper at 87
Frank Lloyd Wright ‐ designed the Guggenheim Museum at age 91
Golda Meir ‐ served as Prime Minister of Israel from age 70 to 76 Jeanne Louise Calment 1875‐1997 (122)
I took pleasure when I could. I acted clearly and morally and Charlene Zola ‐ consulting business, jewelry maker, without regret. I’m very lucky. still active at age
Performance Wisdom Better The ability to put things in context and reach a good decision with less information.
People who occupy positions of responsibility and power tend to be 50+.
The knowledge they have accumulated over the years. Young Aged
48 Rate of Cognitive Decline vs Average in Highest and Lowest Percentiles of Cognitive The Big Five Personality Traits Activity in Later and Earlier Life
• Conscientiousness * Lowest 10% Highest 10% • Organization Cognitive Activity Cognitive Activity • Self‐discipline • Dependability Older Life + 48.4 % ‐ 32.3 % • Drive to achieve
th • * Participants in the Religious Orders Study scoring in the 90 Younger Life + 41.5 % ‐ 31.9 % percentile had an 89% reduction in risk for developing Alzheimer’s.
Rush Memory and Aging Project, Neurology, 2013
Building Cognitive Reserve Compression of Morbidity (James Fries)
• Education – formal schooling but also other kinds of learning • The precipitous downturn among the highly educated • Bilingualism delays the onset of dementia by as much as four years (Fergus Craik) • Training in a second language as well as in music correlates with a slower rate of cognitive • It is possible and desirable to delay the onset of diseases decline (Robert Wilson) • Compress the number of years one spends ill and disabled at the end • The so‐called “change point” in cognitive status (Lei Yu) • cognitive decline does not occur at a steady pace of life • It begins at one rate, then after time it accelerates • More years of independent living translates into benefits for that • More education shifts the change point later in life person and for their family • More learning builds more brainpower to fall back on? • The more educated, the shorter on average their overall suffering • Fewer years of formal education, lower baseline, hit the change point sooner • The risk of death among patients who have Alzheimer’s is greater for those • Bad news: higher education, start decent later; but after CP, decline faster with more education (Yaakov Stern)
49 Methods to Assist Memory Building a Better Brain 10 Ways as We Age (Peter Rabins, Johns Hopkins White Papers)
• Place commonly misplaced items is a designated spot 1. Pick good parents 2. Engage in regular cognitive and physical activity • Write things down (make ”to do” lists) 3. Strengthen and maintain social ties • Say words out load (“I’ve turned off the stove” ‐ an extra verbal cue 4. Get out and explore new things • Use memory aids (cellphone, notepad, wristwatch alarm) 5. Chillax and be happy • Use visual images (Mr. Hackman) 6. Avoid people who are downers 7. Be conscientious and diligent • Group items using mnemonics (“every good boy does fine” – notes) 8. Engage in activities that are meaningful and goal‐directed • Concentrate and relax (George Burns – “kiddo”) 9. Be heart healthy • Get sufficient sleep (consolidation) 10. Eat a diet heavy with fresh fruit, vegetables, and fish 11. Be lucky!
Toward Precision Medicine in Alzheimer’s ACTivity (Reitz, Annals of Translational Medicine,2016)
• “personalized medicine”, “individualized medicine” vs “one‐size‐fits‐ all‐approach” • Considers an individual’s specific makeup of genetic, biomarker, phenotype, and psychosocial characteristics • Allows more accurate diagnosis and more effective disease prevention and treatment as well as understanding of disease onset It is possible that physical and social activity can lead to the development of new brain cells, even in adults. • Examples: Blood typing to guide blood transfusions; specific antibiotic based on known drug sensitivities; testing for specific mutations in BRCA1 and BRCA2 genes in breast cancer patients
50 Precision Medicine (PM) in Alzheimer’s Monkeying Around with Genes
• Applying PM to a complex disorder like AD is feasible • Huntington’s disease • Large‐scale biological databases • Likened to having Alzheimer’s, Parkinson’s, and ALS all at once • Variety of high‐throughput biomarkers (proteomics, metabolomics,genomics) • Scientists know the cause ‐ a mutation in a single gene • Advances in computational tools necessary for massive data analyses • No treatment or cure • Clinical and pathological heterogeneity of Alzheimer’s • Anthony Chan developed the first transgenic monkey model of • Several phases from latent symptomology to full clinical expression Huntington’s • Pathology intra‐ and extra‐cellular, neuronal loss, synapse loss, activated glia • 10 years developed symptoms similar to humans • Frequent clinical and pathological overlap with Lewy Body and cerebrovascular diseases • MRI of brains revealed changes similar to humans • Expanded colony will allow testing of different treatments
The Grand Challenge: How Do Genes and the Environment Interact? Tomorrow’s Treatments
• Where and when does gene expression important for memory function • Ultimately, the path to effective new treatments is through clinical occur? trials. Trials are recruiting people with Alzheimer's and mild cognitive impairment (MCI), as well as healthy volunteers to be controls. • How are cells expressing these genes influenced by the environment to either maintain the brain in top‐notch mode of healthful memory • Find out more about participating in a clinical study through the function or instead to head toward dysfunction? Alzheimer’s Association TrialMatch service , a free tool for people with Alzheimer's, caregivers, families and physicians to locate clinical trials • Where do we spot points of vulnerability that can make the difference based on personal criteria (diagnosis, stage of disease) and location. between healthy memory and diseases that impair memory?
51 1. Spain: Phase 2 clinical trial evaluating active immunotherapy, or vaccine, ABvac40. ~ 120 participants, some will not yet have developed The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Trial Alzheimer’s Vaccines symptoms of dementia — called prodromal patients — The A4 trial is studying the effectiveness of solanezumab, a drug targeting beta-amyloid, in Update and some will have mild cognitive impairment (MCI). 1,150 symptom-free volunteers whose PET scans show abnormally high levels of beta- ~ Confirming safety data, evaluate cognition amyloid in the brain. High levels of beta-amyloid in the brain increase the risk for developing Alzheimer's disease. Researchers hope that early intervention in individuals at 2. AADvac1, a vaccine against tau protein that increased risk of developing Alzheimer's will prevent the cognitive decline of this accumulates and forms tangles devastating and ultimately fatal disease. ~ Showed therapeutic potential in Alzheimer’s disease (AD) and frontotemporal dementia (FTD) in Phase 1
TOMMORROW Trial 3. University of California, Vaccine and oral medication that The TOMMORROW Trial includes 3,500 asymptomatic individuals, some of whom have the target amyloid beta, the primary component of amyloid Alzheimer's risk gene apolipoprotein E e4 (APOE-e4) or the TOMM40 risk gene. The trial plaques in AD will explore whether the anti-diabetes drug pioglitazone can prevent mild cognitive ~ Participants randomly assigned for five to eight years. impairment due to Alzheimer's disease. Studies suggest that pioglitazone may decrease ~ The vaccine assists in the development of amyloid beta inflammation and beta-amyloid levels in the brain, improve blood flow to the brain and antibodies, and the oral medication blocks an enzyme that increase the brain's ability to use glucose to fuel nerve cells. makes amyloid beta.
Maintain Your Mind and Brain
Mind and Bind Young Blood? Stay intellectually and socially engaged Education is a reverse risk factor for cognitive decline; increase cognitive reserve; Research Nun study suggests additional possibilities of brain resistance to pathology; Alkahest in San Carlos, CA Say “ I do” ‐ 9 out of 10 married women live to 65; only 8 out of 10 single or divorced women live to same age. Young plasma boosted cognition in old mice Pump not Rump
Exercise (oxygen; growth‐inducing proteins for neurons) Clinical Trial Most major studies point to simply walking; associated with less cognitive Blood donated by healthy young people decline over the years; and more physically fit individuals experience less brain shrinkage of regions involved in learning and memory associated with aging; 18 people with mild or moderate AD Leisure‐time physical activity (breathless, sweat) 2x week at midlife reduced risk; Caregivers reported better at daily One leisure activity associated with increased likelihood of developing AD? But no better on cognitive tests Choose to Snooze Without adequate sleep, concentration suffers (8 hours?)
Planning more clinical trials Lessen your Stressin’ Excess stress ‐> stress hormone ‐> memory loss
52 One last point…
Thank You!
53 Remembering, Forgetting and Protecting the Aging Brain – Stuart Zola Bibliography
Aamodt, Sandra and Wang, Sam Welcome to Your Brain – Why You Lose Car Keys but Never Forget How To Drive Bloomsburt, New York, 2008
Bherer, Louis, Kirk Erickson and Teresa Liu‐Ambrose A Review of the Effects of Physical Activity and Exercise on Cognitive Functions in Older Adults J. Aging Research, v2013, pp 1‐8, 2013
Budson, Andrew E., and Maureen K. O’Connor Seven Steps To Managing Your Memory – What’s Normal, What’s Not and what to do About It Oxford University Press, 2017
Buzan, Tony The Mind Map Book – Unlock Your Creativity, Boost Your memory, Change Your Life Pearson Education Group, Essex, UK, 2010
Buzan, Tony Ageproof Your Brain Proactive Press, Cardiff, UK, 2012
Cimons, Marlene Genes Don’t Doom Your Weight – Obesity is 80% genetic and 100% environmental Atlanta Journal‐Constitution/ Washington Post, Aug 22, 2017
Clear, James The Science of Sleep – A Brief Guide JamesClear.com, Blog, 2016
Cohut, Maria Walk 4,000 steps every day to boost brain function – walking supports resilience of function MedicalNewsToday.com, Dec 28, 2017
di Perna, Robin and Alan di Perna The Science of Mindfullness – How does meditation affect and even improve your brain? Mindfulness An Everyday Guide, Athlon Publications, Nashville, 2017
Daniels, Patricia S. Your Brain: A User’s Guide – 100 things you never knew about your brain National Geographic Partners, LLC, Washington, DC, 2018
Farr, Christine Can Digital Therapeutics be as Good as Drugs? – Entrepreneurs are betting on apps that improve – or just replace – prescription medications TechnologyReview.com, MIT, Cambridge, MA, April 7, 2017
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Genova, Lisa Feel Helpless Against Alzheimer’s Disease? You can do something to prevent it. Ideas.TED.com, January 10, 2018
Green, Holly G. Using Your Brain to Win The Human Factor, Inc., New York, 2013
Haliday, Glenda Pathology and hippocampal atrophy in Alzheimer’s disease The Lancet Neurology, v16 pp 862‐864, 2017
Harrar, Sari Avoid Alzheimer’s – Understanding Your Risk Factors Can Stave Off Memory Loss AARP Bulletin, pp 16‐24, December, 2017
Horsley, kevin Unlimited Memory – How to use advanced learning strategies to learn faster, remember more TCK Publishing, Granger, IN, 2016
Jaeggi, Susanne, Martin Buschkuehl, et al. Short‐ and long‐term benefits of cognitive training Proceedings of the National Academy of Sciences, v108, pp 10081‐10088, 2011
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Kuhar, Michael The Addicted Brain – Why We Abuse Drugs, Alcohol and Nicotine FT Press, New Jersey, 2012
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Malone, Michael The Guardian of All Things – The Epic Story of Human Memory St. Martin’s Press, New York, 2012 55
Medina, John Brain Rules – 12 Principles for Surviving and Thriving Pear Press, Seattle, 2014
Morris, Martha Claire The MIND diet and Best Diets Overall USNews.com Health blog, 2017
Napier, Nancy The Myth of Multitasking – Think You Can Multitask Well? Think Again! Psychology Today, May, 2014
Rabins, Peter Memory – Guide to Alzheimer’s and dementia University of California Press, Berkeley, 2018
Sapolsky, Robert Behave – The Biology of Humans at Our Best and Worst Penguin Press, New York, 2017
Stetka, Bret In Search of the Optimal Brain Diet Scientific American, Mysteries of the Mind, pp 69‐75, 2017
Stickgold, Robert Sleep on it! – How sleep balances hormones and boosts immunity among other things Scientific American, Mysteries of the Mind, pp 54‐59, 2017
Yapko, Michael Mindfulness and Hypnosis – The Power of Suggestion to Transform Experience W. W. Norton & Company, New York, 2011
Zola, Stuart Maximizing. Memory – Two new brain behavioral approaches to mitigate memory impairments Pan European Networks: Science and Technology, v23, pp. 1‐2, 2016
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IBP programs are designed to be based on the best available evidence from current scientific research. However, the interpretation of evidence-based research may vary among researchers. The views and opinions expressed in this program are those of the presenter and do not necessarily reflect the views and opinions of IBP.
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Remembering, Forgetting and Protecting the Aging Brain – Stuart Zola Self‐test
1. The brain weighs only 3‐4 pounds but uses ___ of the body’s blood, oxygen and energy. a. none b. 70% c. 50% d. 20%
2. One of the most important brain structures for memory is the a. decimal b. cerebellum c. hippocampus d. none of the above
3. Working memory, short‐term memory and immediate memory a. involve pretty much the same brain regions b. are important in setting the stage for long‐term memory c. have fairly limited capacity for holding information d. all of the above
4. There are many different dementias, but one accounts for about 70% of cases a. Huntington’s disease b. Alzheimer’s disease c. Biswangus disease d. None of the above
5. The biggest positive risk factor for Alzheimer’s disease is a. age b. bullet wound to the shoulder c. childhood emotional trauma d. advanced education
6. The relationship between sugar and cognition: a. no relationship b. scores on memory tests decline as blood sugar raises c. b and d d. the risk of Alzheimer’s tumbles as blood sugar dips
7. Alcohol a. all of the below b. heavy use can lead to addiction c. withdrawal and sudden abstinence can be fatal d. interferes with many elements of our biochemistry
8. Stress a. has no real impact on the cardiovascular system b. can directly affect memory and problem solving c. as long as it is chronic, is okay d. only impacts older people
9. Mindfulness refers to a. watching someone else’s child b. has no relation to meditation c. being consciously aware of thoughts and emotions d. can only be practiced in a dark quiet environment
10. Exercise a. provides the brain with greater access to oxygen b. 4 hrs after studying can boost memory c. can help management of high blood pressure d. all of the above