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Aging Life Care AssociationOctober 2017

“Brain Fitness”Jason Brandt, Ph.D.

Professor of Psychiatry & Behavioral Sciences and NeurologyDirector, Division of Medical Psychology

The Johns Hopkins University School of Medicine

Late 2000’s

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Early 1990’s

Late 1980’s

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Early 1980’s

Late 1970’s

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How Many of You Have Experienced the Following?

• You were just introduced to someone two minutes ago and now you can’t recall his/her name.

• You walk into a room in your house to get something and, when you get there, you forget what you were looking for.

• You plan to stop at the supermarket to pick up a few items on the way home, and you go directly home instead.

• You find yourself groping for the right word; it’s on the “tip-of-your-tongue.”

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Prevalence of Memory ComplaintsAmong Community-Residing Older Adults

(Salthouse, 1991)

• “Do you have memory problems?”– 67% say “yes”

• “Do you have memory problems compared to most people your age?”– 6% say “yes”

Prevalence of Memory ComplaintsAmong Community-Residing Older Adults

(Jorm et al., 1994)

• Large sample of adults, age 70 and older• 62% reported that memory was currently

worse than earlier in their lives– 6% believed memory difficulties interfered with

their daily lives

• 30% reported that they couldn’t think or reason as well as earlier in life– 5% believed this interfered with daily life

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Major Cognitive Changes in Normal Aging

• Reduced speed of information processing• Reduced working memory capacity

– Problems “multi-tasking”

• (Yes, these are normal!)• Preserved semantic memory

– Vocabulary– Accumulated world knowledge– Wisdom?

Salthouse (2006)

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Goals of Brain Fitness Interventions

• To prevent Alzheimer’s disease and other memory-impairing disorders

• To reverse the effects of normal aging

• To maximize cognitive functioning and enhance quality of life

Goals of Brain Fitness Interventions

• To prevent Alzheimer’s disease and other memory-impairing disorders NO

• To reverse the effects of normal aging NO

• To maximize cognitive functioning and enhance quality of life YES

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Factors Affecting Memory in Neurologically Normal Adults

• Genetics• Depression• Stress, anxiety• Medications

• Effort• Attention• Encoding Strategy

Treatment of Memory Impairment

• Three Basic Strategies– Medications, Vitamins, and Nutrients– Memory Retraining

• Methods of vanishing cues, errorless learning, etc.– Extremely laborious– Little evidence of transfer to everyday memory

– “Memory Prostheses”• Calendars, reminder notes, electronic cuing

devices, etc.• Patient and family support

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Treatment of Memory Impairment

• Three Basic Strategies– Medications, Vitamins, and Nutrients– Memory Retraining

• Methods of vanishing cues, errorless learning, etc.– Extremely laborious– Little evidence of transfer to everyday memory

– “Memory Prostheses”• Calendars, reminder notes, electronic cuing

devices, etc.• Patient and family support

Medications, Vitamins & Nutrients– Alzheimer’s medications

• Cholinesterase inhibitors– donepezil (Aricept®), rivastigmine (Exelon®),

galantamine (Reminyl®, Razadine®)

• NMDA receptor antagonists– Lower glutamate– memantine (Namenda®)

• Do not improve memory in persons without dementia

– Nonsteroidal anti-inflammatory drugs (NSAIDs) and cholesterol-lowering drugs (statins)

• Little evidence of effectiveness

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Adverse Cognitive Effects of Medications in Older Adults

• Beers List of potentially inappropriate medications for use in older adults

• American Geriatrics Society, updated 2012• Many have anticholinergic properties• Many have high potential for drug-on-drug

interactions• If you are taking any of these medications, consult

your physician. DO NOT DISCONTINUE USE OF ANY MEDICATION WITHOUT THE APPROVAL OF YOUR PHYSICIAN.

Medications, Vitamins & Nutrients

– Hormones• Estrogen replacement therapy

– Promising, based on epidemiological studies– Ineffective (and possibly damaging) in clinical trials– May depend on when taken vis-à-vis menopause

• Testosterone supplementation– Only anecdotal evidence

– Herbal preparations• Gingko biloba, etc.• Little evidence of effectiveness

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Forget About Ginkgofor Memory Enhancement

(Solomon et al, JAMA, 2002)

• Randomized, double-blind, placebo-controlled study of 230 community residents over age 60

• Administered tests of learning, memory, attention, concentration, naming and verbal fluency at entry and after 6 weeks of “treatment”

• Received 40 mg. ginkgo biloba (N=115) or placebo (N=115), 3 times a day (120 mg. is recommended dose)

Forget About Ginkgofor Memory Enhancement

(Solomon et al, JAMA, 2002)

• 203 participants completed study• Better performance in both groups

after treatment than before treatment (practice effect)

• No difference between groups on any of the neuropsychological tests, self-reports of memory efficiency, or rater reports

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Treatment of Memory Impairment

• Three Basic Strategies– Medications, Vitamins, and Nutrients– Memory Retraining

• Methods of vanishing cues, errorless learning, etc.– Extremely laborious– Little evidence of transfer to everyday memory

– “Memory Prostheses”• Calendars, reminder notes, electronic cuing

devices, etc.• Patient and family support

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Figure from: Salthouse (2006)

Sharpening Your Memoryis Big Business!

• Internet search on May 29, 2013• Searched on Google for “improve memory”• Found approximately 19,400,000 English

language web pages• Most advertise unproven commercial

products• SAVE YOUR MONEY!• Invest in a date book and memo pads

instead

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Brain Fitness on the Internet

• Appeals to “neuroscience”• Vigorous advertising campaigns

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“Lumosity Game Developer Agrees to $2 Million Settlement”

By the Associated Press, January 5, 2016

Lumos Labs, the developer of Lumosity “brain training” games, will pay $2 million to settle accusations it misled customers about the cognitive benefits of its online apps and programs. The Federal Trade Commission said on Tuesday that ads deceptively suggested that playing the games a few times a week could increase work and school performance, and even delay conditions like dementia. Lumos Labs must contact customers and offer them an easy way to cancel their subscriptions, which range from $15 to $300. The $2 million will be refunded to customers. Jessica L. Rich, director of the F.T.C.’s Consumer Protection Bureau, said the company “simply did not have the science to back up its ads.” Only products that have been reviewed by the Food and Drug Administration can claim to treat or prevent serious diseases or conditions.

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How to Maximize Learning and Memory

• Make sure you can see and hear!• Minimize distractions while learning

– Facilitate attention

• Avoid alcohol and other drugs while trying to learn something new

• Avoid “cramming”– Spaced learning is superior to massed

learning

• Minimize retroactive interference– Go to sleep after studying

How to Maximize Learning and Memory

• Process material “deeply”– Link it to ideas already known– Make it relevant; create personal narratives, and

stories

• Use mnemonic devices– Every Good Boy Does Fine– ROY G. BIV– Thirty days hath September, …

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How to Have aGood Memory as You Age

• Inherit good genes!• Maintain good nutrition• Control blood pressure• Take all medications only as

prescribed• Avoid excessive alcohol

How to Have aGood Memory as You Age

• Keep mentally active– Whatever you do should be fun, challenging, and

stimulating.– You should like to do it, and do it often.

• Keep physically active– Aerobic exercise and strength training– Work with fitness coach or in a group– In general, what’s good for the heart is good for

the brain.

• Keep socially active– Communicate frequently with friends and family– Cultivate new relationships

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How to Have aGood Memory as You Age

• Seek treatment for depression, anxiety, or other psychological disorders– Major depression is a major cause of memory

impairment.– Stress hormones (e.g., cortisol) can damage brain

cells.

• Forgive yourself.– You’re allowed to forget once in a while!

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Mediterranean Diet• Large amounts of

legumes, cereals, nuts/seeds, fruits, vegetables, fish, and polyunsaturated fats (e.g., olive oil)

• Small amounts of meat, dairy products, saturated fats.

• Low to moderate amounts of wine

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Mediterranean Diet• Scarmeas et al. (2006)• Studied 1,984 elderly New

Yorkers– 10% had AD

• Rated diets 0-9, based on how closely they adhered to Mediterranean diet (MD)– Those in top third had a 68%

lower risk of AD than those in the bottom third.

– Those in the middle third had a 53% lower risk.

Mediterranean Diet• Scarmeas et al. (2007)• Studied 192 New Yorkers with AD• Followed for more than 4 years, on average• 85 patients died during the study period

– Those who closely followed the MD were 76% less likely to die

– Those who closely followed the MD lived an average of 4 years longer

– Moderate adherence to the MD added an extra year of survival

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Glucose and the Brain in AD• The brain requires a constant supply of glucose for

normal function– >90% used for synthesis of adenosine triphosphate (ATP)– Brain’s glycogen stores sufficient for only 5 min. of normal

function

• Cerebral glucose metabolism is known to be abnormal in even very early AD

Alternative Fuels for AD• Glucose is the primary and preferred fuel for

most cells, including neurons.• Supplying an alternative fuel could bypass

problem of insulin deficiency and insulin resistance in AD brain

• Humans are programmed by evolution to switch to use of alternative fuels during starvation, when glucose stores have been used up

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Ketone Bodies• Acetoacetate, β-hydroxybutyrate (BHB),

acetone• Produced in the liver by fat metabolism

– Usually when glucose stores are limited• Prolonged fasting, starvation, severe anorexia nervosa

• Early in human evolution, ketosis was probably a valuable survival mechanism to fuel brain in times of food scarcity

• Hypothesis: Ketosis can be used as an alternate source of energy for the brain in AD

Medium Chain Triglycerides are Converted to Ketone Bodies by the Liver

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Ketogenic Diet• 4:1 ratio of fats to proteins and

carbohydrates– The typical Western diet is >50%

carbohydrates

• Very complex and precise– All foods must be carefully weighed and

measured– Usually requires strict supervision by a

professional nutritionist or dietician

Ketogenic Diets for MCIand Alzheimer’s Disease

• Patients with Alzheimer’s disease show:– Reduced cerebral glucose metabolism– Impaired insulin and insulin-like growth factor

expression (type 3 diabetes)

• Ketone bodies (BHB; AC-1202) shown to correlate with improvement on Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog).

• Ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of AD.

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2005

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Modified Atkins Diet (MAD)• A moderate ketogenic diet proposed in

2003 by Eric Kossoff at Johns Hopkins University

• 10-20 grams net carbohydrates per day, depending on age of patient– Net carbs = Total carbs – Fiber

• No weighing foods• No hospital admission• No fasting• 1:1 to 2:1 ratio

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Study Design: Eligibility• Recruit 60 persons with MCI or early AD

– Age >60– CDR Global Score = 0.5 or 1– MoCA score between 18 and 25– Normal blood labs– Assent of primary care physician– Cognitively normal, cohabitating study

partner• MMSE-2 T-score > 40 for age and education• Must help with meal preparation and adherence

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Study Design: Study Contacts• Eligibility Screening by Telephone• Enrollment/Baseline Visit

– Neuropsychological testing– Blood sample– Randomized to MAD or “NIA Healthy Eating After 50” Diet

• Group Educational Session (week-0)• Week-3 follow-up• Week-6 follow-up

– Neuropsychological testing

• Week-9 follow-up• Week-12 follow-up / Close-Out

– Neuropsychological testing– Blood sample

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Thank You!