Your mind matters. Here's how to stay sharp.Prof Yoram Barak, MD, MHA.

“Dementia Beyond Disease”

We tend to presume that science and technology will create the future brain health…(Dr G. Allen Power)

Our “social” brain must be harnessed in order to truly achieve a comprehensive humane well-being.

This presentation is partly based on work by Dr Yakir Kaufman (Jerusalem) and Dr Max Cynader (Vancouver).

The secret to increasing brain function is growing neurons.More neurons means a better ability to learn and to remember.

Get quality restOne way to grow neurons? During the day, while you learn, you grow neural

connections in your brain. Then at night, you replay the day's memories while you sleep, helping neurons to wire and fire together.

Take the blues seriouslyA 2010 study published in Cognitive, Affective & Behavioral Neuroscience showed

people with depression performed worse on cognitive tasks than their non-depressed counterparts. 'Treat the depression and you can improve the cognitive

function,' says Aaron Newman, a neuroscientist and associate professor at Halifax's Dalhousie University.

Manage stressWhen we're agitated, our bodies flood our brains with cortisol. The hormone

attaches to receptors in our neurons, which allows more calcium to pass through their membranes. Neurons overloaded with calcium fire too rapidly. That hyper

firing kills neurons.

PlayResearch from the Berlin-based Max Planck Institute for Human Development and

two other German institutions showed that regularly playing Super Mario 64 increased study participants' brain volume in the regions that control memory and

spatial thinking.

Drink your coffeeCoffee contains polyphenols, antioxidant compounds that may protect the

hippocampus and the cortex, areas that are important for memory. Three to five cups a day is ideal.

Brush upA study published in the Journal of the American Geriatrics Society found that

people with none of their own teeth performed 10 per cent worse on memory tests than those with some natural teeth. Researchers have yet to determine why.

Monitor your hearingA 2013 Johns Hopkins study concluded that cognitive decline progressed 30% to

40% faster for people with hearing loss than for those with normal hearing. Treating impairment can improve cognitive ability.

Avoid smokingThe cortex, the bumpy surface layer of the brain, naturally thins as we age. Smoking

hastens this thinning, which is associated with cognitive decline.

BACKGROUND (1)

• The prevention of dementia, and particularly of Alzheimer’s disease, is a major challenge for researchers and clinicians.

• Currently there are 1,278 clinical trials listed on ClinicalTrials.gov

• In the last 30 years not a single new molecule was approved by the FDA for Alzheimer’s disease.

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Multiple factors causing disease

DementiaDiet

Stress

Depression

Health behaviors

Environmental exposure

Genetics

Pathogens

Lifestyleocc.,social,

physical etc.

Cause of disease is multifactorial

therefore effective prevention and treatment must be integrative

Meaning

Loneliness

Metabolic

ר יקיר קאופמן"ד

Nine Risk Factors May Explain Two Thirds of AD Cases

• We do NOT need to know the cause of Alzheimer’s disease in order to plan preventive strategies.

• Protective and Risk factors are our focus.

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Nine Risk Factors May Explain Two Thirds of AD Cases

Risk factors include:

• Obesity

• carotid artery narrowing

• low educational achievement

• Hyperhomocysteine

• Depression

• Hypertension

• Frailty

• current smoking

• type 2 diabetes (only in Asian populations).J Neurol Neurosurg Psychiatry. August 20, 2015.

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Antihypertensive medications (1)

The largest body of evidence since 1972 has focused on the treatment of hypertension and its effects on preventing or delaying the onset of AD.

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Antihypertensive medications (2)the future ?• Timing:

• For each additional year of antihypertensive treatment in middle-age there is a reduction in the risk of incident dementia. • In one large study the risk for dementia in subjects

with more than 12 years of treatment was lower than for hypertensive participants (hazard ratio for AD: 0.35; 95% CI: 0.16–0.78), and was similar to the normotensives

• Specificity of Drugs:

• ARS … modulation of the renin-angiotensin system (RAS)

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Diet & nutrients (2)

• One of the recent concepts regarding the relationship between diet and the risk of developing AD is that of dietary pattern (DP) analysis.

• DP analysis utilizes a broad view of nutrition.

• Humans eat meals with complex combinations of nutrients or food items that are likely to be synergistic.

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Don't count on superfoodsStudies have shown that turmeric, for example, breaks up brain plaque (which has

been linked to Alzheimer's), but it's no cure-all. 'It's not the food that's beneficial; it's the chemicals in it,' says Newman. It's impossible to get a high enough concentration

of those chemicals in your diet to recreate lab results.

Estruch R et al.

The New England Journal of Medicine, Feb 2013

Primary Prevention of Cardiovascular

Disease with a Mediterranean Diet

A randomized trial of this diet pattern for the primary prevention of cardiovascular events was conducted.

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Ramón E, et al. N Eng J Med, 2013

Mediterranean Diet and Age-Related Cognitive Decline:A Randomized Clinical Trial

CONCLUSIONS AND RELEVANCE

In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated

with improved cognitive function.

JAMA Intern Med. 2015;175(7):1094-1103.24

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Cognitive engagement

• Valenzuela and colleagues (2008) systematically reviewed recent evidence linking mental activity and dementia risk, which commonly invokes ‘brain reserve’ as the mediating construct.

• Significant protective risk ratios for individuals with higher mental activity in the range of 0.41–0.67 were demonstrated in research. • In addition, a number of these studies point to dose-

dependent effects.

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Get ZenMeditating for half an hour a day, for eight weeks, has been shown to grow grey

matter in the hippocampus, which may improve memory and learning.

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Break a sweatOne-hour weightlifting sessions, twice a week, have been shown to slow the

progress of mild cognitive impairment

Physical activity (2)“A sound mind in a sound body is a short but full description of a

happy state in this world.”John Locke; English empiricist philosopher (1632–1704)

Identification of elderly individuals who consistently demonstrate intact cognition demonstrated:

maintainers had a unique profile associated with being a maintainer and not a decliner :

Weekly moderate or vigorous exercise (OR: 1.31)

Not smoking (OR: 1.84)

Exercising translates into DAILY 30-45 minutes fast walking. “Breathing” measure

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Physical activity (3)“A sound mind in a sound body is a short but full description of a

happy state in this world.”John Locke; English empiricist philosopher (1632–1704)

An analysis of 13,500 participants in the Nurses’ Health Study found that the likelihood of ‘successful survival’ (living past 70 years of age in general good physical and mental health) was nearly doubled for women who had been in the highest quintile of overall physical activity 10–15 years earlier, than for the most sedentary participants.

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Loneliness

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Build friendships, volunteer.As little as 10 minutes of socializing a day improves cognitive performance.

Volunteering has been shown to increase successful ageing.

Social isolation in old age has been associated with risk of developing dementia.

• Wilson (Rush Alzheimer’s Disease Center, Chicago) and his fellow researchers aimed to test the hypothesis that loneliness is associated with increased risk of Alzheimer's disease.

• The risk of Alzheimer's disease doubles in lonely persons.• Loneliness did not change significantly over the study

period so that lonely elderly in essence remained lonely for many years.

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Social isolation

• Objective markers such as:• small social network

• Unmarried

• participating in few activities with others

• are now confirmed as associated with increased risk of Alzheimer's disease.

• It is intriguing to follow the way knowledge accumulated rapidly to unravel the link between these social markers and dementia.

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Purpose in Life

• A dictionary definition of purpose will incorporate the following elements:" The reason for which something exists or is done, made, used. An intended or desired result; end; aim; goal. Determination; resoluteness."

• It is hard to imagine a purpose in life, especially for older adults, that does not involve a social aspect.

• Indeed, when researchers looked at the purpose in life of nearly 1,000 people over a seven-year period those with a high score on the purpose in life measure were approximately 2.4 times more likely to remain free of Alzheimer's disease.

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Hope at last !

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New Insights into the Dementia Epidemic

Larson et al, Nov 2013

Although demographics will drive an increase in the number of dementia cases, recent reports — generally based on population-based community studies or survey data —point to declining age-specific prevalence or incidence rates among people born later in the first half of the 20th century.

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New Insights into the Dementia EpidemicLarson et al, Nov 2013

• They conclude that populations born later have a lower risk of dementia than those born earlier, probably because of:• higher education levels

• better prevention of vascular disease

• even in the face of countervailing factors such as diabetes and survival after stroke, which could increase age-specific dementia prevalence.

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Hope at last !

• The study in England and Wales published in July of 2013 made the following headline in the New York Times: "Dementia Rate Is Found to Drop Sharply…“

• The article in the New York Times goes on to say that this is the strongest, most credible evidence yet. At the close of the article Dr. Anderson, of the National Institute on Aging, said the news was good. “we are beginning to see that more and more of us will have a chance to reach old age cognitively intact, postponing dementia or avoiding it altogether. That is a happy prospect.”

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Thank you for your attention…

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