Jennie L. Wells MSc, MD, FRCPC, FACP

Associate Professor of Medicine

Chair, Division of Geriatric Medicine

Schulich School of Medicine and Dentistry

Western University

31 May 2017

Therapeutic Recreation Ontario Conference

Before Pills . . . Or Why

Leisure is Important!

Disclosures I am currently the site PI or sub-I for pharma

sponsored clinical trials for dementia medications.

(Roche, Eisai, Lilly, Merck, Biogen, Transtech,

Boeringer)

In the past 3 years I have been the sub-I site

investigator for clinical trials sponsored by TauRx,

Lundbeck, Genentech, Bristol-Myers-Squib, Forum.

In the past 3 years I have not had any industry

sponsored honoraria.

I am a past employee of Pfizer Inc and own

employee stock.

Before Pills . . . Why leisure is important . . .

Learning objective:

You will be able to discuss the evidence and appreciate the important

role for Leisure Recreation Therapists to enhance the delivery of non-

pharmacological interventions of exercise, brain activity, meditation,

and diet to delay or evade the onset of dementia, death, and disability.

Outline:

1. Introduction: why is this important?

2. Case – “food for thought”

3. Nutrition

4. Brain exercise, ”thinking,” meditation, music

5. Physical exercise

6. Case discussion & Summary

Introduction—why is this important?

Over the past 25 years we’ve learned lots.

The causes of AD are complex and

multiple.

The baby boomers are aging.

We still don’t have a cure . . .

AD is a neurodegenerative disease that,

on average progresses to death in 6-12

years.

Before Pills . . .

If we can delay the onset of dementia by 5 years, we can reduce the prevalence by 57% and cut the cost by ~50%

(Sperling RA 2012)

Before Pills . . . But, “up to half of AD cases worldwide are . .

attributed to modifiable factors. . . . 1 million AD

cases could be prevented globally if a 25%

reduction in physical inactivity could be achieved in

the world population.”

Lautenschlager 2013

The time to act is now!

Case : Mrs. Toula

Sectamauve Mrs. TS is a 75 yo homemaker with fibromyalgia,

macular degeneration, OA, Depression/anxiety, walks with a cane, lives alone, says she is lonely. She is referred by her doctor to the Kiwanis for “activation.”

No home help; independent IADLS/ADLS. 1 fall with ER visit this year.

“I exercise walking in the Grocery store.”

Strategies? Barriers? Motivators?

Risk Factors for AD

Age

Family History

Gender

Stroke

Down’s syndrome

Head Trauma

Low level of

education

Hypertension

Blass and Poirier, 1996; CSHA 1991(Canadian Study on Heath and Aging)

New: Poor nutrition

Low level of exercise

Risk Factors for AD—what can

we change?

Age

Family History

Gender

Stroke

Nutrition

Level of exercise

Down’s syndrome

Head Trauma

Low level of

education

Hypertension

Blass and Poirier, 1996; CSHA 1991

^ new

What we eat:

Estuch et al. NEJM 2013: Primary Prevention of Cardiovascular Disease with Mediterranean Diet (MD)

“Even the best available drugs, like statins, reduce

heart disease by about 25 percent, which is in the

same ballpark as the Mediterranean diet,” --Dr. Walter

Willett, professor of epidemiology & nutrition at Harvard School of

Public Health.

. . that means that for every 1,000 people who

followed the Mediterranean diet, three people each

year avoid a heart attack or stroke because of the diet.

What we eat: Estruch et al 2013;

Mediterranean Diet (MD) and Cardiovascular Prevention

7447 persons age 55-80 were followed for 4.8 years.

Randomized to MD with extra-virgin olive oil (MDO) (n=2543); MD with nuts (MDN)(n=2454); or (C) control (n=2450)-- low fat.

All received dietician education.

The MD groups received 1 l of olive oil or 75g of mixed nuts (walnuts, hazelnuts, almonds) at no cost. Control (C) received a small non food gift.

Myocardial infarction, stroke or death were primary end points.

Events: MDO-96, p=0.009; MDN-83, p=0.02; C-109.

For just stroke: MDO 49, p=0.03; MDN 32, p=0.003; C 58.

What we eat:Scarmeas JAMA 2009:

Physical Activity, Diet, & Risk of AD

Prospective cohort of 1880 community elders NYC

with no dementia, average age 77, followed for 14 yrs.

Interviewed every 1.5 years, followed for activity &

diet.

Those with the highest adherence to Mediterranean

diet & exercise had the highest probability of

remaining AD-free.

Alzheimer Disease Incidence by High or Low physical Activity

Scores & by Mediterranean-Type Diet Adherence Score

Scarmeas JAMA 2009

MIND Diet study (Morris et al 2015)

Prospective observational study, 4.5 years, 923 subjects age 58-98. Food questionnaires analyzed based on adherence to the MIND diet and DASH diet.

Covariates: age, education, leisure activities, depression,stroke, hypertension, heart disease, BMI, diabetes, medication use.

144 incident cases of AD were diagnosed.

The 1/3 with highest adherence to the MIND diet had lowest rate of AD (HR 0.47, CI .26-.76); moderate adherence DASH-HR 0.67, CI .44-.98.

DASH only—only highest adherence group, HR .61, CI .38-.97.

Mediterranean only—HR .46, CI .26-.79.

Survivor function for incident Alzheimer Disease for the Mediterranean- DASH Intervention for Neurodegenerative

Delay (MIND) diet (tertile adherence)

MIND study (Morris 2015)

What we eat: Meta-analysis(Psaltopoulou et al Annals of Neurology 2013)

Interpretation: “Adherence to a Mediterranean Diet

may contribute to the prevention of a series of brain

diseases.”

22 eligible studies: 11-stroke; 9 depression; 8 cognitive

impairment; 1 Parkinson’s Disease.

The Mediterranean Diet consistently was associated

with a reduced risk for:

Stroke (RR .71 CI ,43-.83)

Depression (.68, CI .54-.86)

Cognitive impairment (.60, CI .43-.83)

What we think:

• Willis et al. JAMA 2006: Long-term effects of cognitive training on everyday functional outcomes in community.

• Randomized single blind study of 2832 people, mean age 73.6,

community dwelling in 6 cities in USA, MMSE > 22, 67% retention.

• Excluded if had diagnosis of AD, medical conditions causing disability,

imminent death; or if had hearing loss/blindness.

• Ten training sessions given for each training group: memory, reasoning,

speed of processing were given and 4 booster sessions were given at 11

& 35 months. The control group had no contact.

• At 5 years all trained groups better cognition than the control group.

• At 5 years, the reasoning trained group had less functional decline.

What we think:• Herholz et al review article 2013: observational,

longitudinal studies with positive cognitive effect

of:

• Life long learning

• Practicing languages throughout life

• Music practice

• Specialized training

• New research to include imaging coupled with

activity.

• Brain plasticity is modulated in animal models by

reward neurotransmitters. The role of reward

networks in human training needs to be explored.

What we think:Khalsa, D. Meditation & AD Prevention: the forgotten factor. P1-104, AAIC 2012.

A review of the literature: cognitive studies, imaging

studies, and other outcomes.

• Meditation slows aging by enhancing telomere length.

• Reduces inflammatory markers.

• Enhances memory.

• Reduces depression, stress, and hypertension.

• Enhances brain volume (Pagnoni 2007).

• Pilot study, 2012—reduces negative emotions in

persons with AD.

What we think: Potential benefits of

mindfulness-based interventions (MBI) in MCI & AD: an

interdisciplinary perspective (Larouche et al 2015)

Stress, depression, & metabolic syndrome accelerate

MCI & AD.

MBI reduces blood pressure, cortisol, inflammation,

regulates serotonin, & white matter hyperintensities.

Future research must achieve deeper understanding of

mechanism & bridge the gap with in fields of neuro-

science as well as basic and clinical knowledge.

What we think:

Sung H-C et al. J Clin Nurs 2010. A preferred music listening intervention to reduce anxiety older adults with dementia in nursing homes.

n=29 received a 2X/wk 30 min music session while

controls (n=23) had usual care with no music.

preferred music group had significantly lower anxiety

compared to those who received standard care. (p=0.001)

What we think . . . Ridder et al Aging & Mental Health 2013: RCT of

music therapy vs usual care of persons with agitation and dementia.

42 persons had 6 weeks of 2x/wk music sessions vs

standard care.

Agitation decreased in the music group p=0.027,

effect size (0.5)

The music group received less psychotropic

medication.

What we think (and do):Dr. Nina Kraus personal communication 2013:

Music engages sensory, cognitive and reward brain

circuitry. There is over-lap in brain areas for speech and

music.

OPERA: Overlap, Precision, Emotions, Repetition,

Attention.

Even if engaged in music for the first time in older life,

improvement is seen.

Adults aged 60-85 with no musical training improved on

processing speed & memory after 3 months of 30 min

piano lessons & 3 hours per week of practice.

What we think (and do):Satoh et al 2014:

Dual training with physical exercise & music:

119 subjects, age 65-84 were enrolled in once per

week physical exercise with trainer with music

accompaniment for 1 year or the same exercise

without music.

MRIs & cognitive tests done pre and post

The group with physical exercise with music had more

positive effects on cognitive function than exercise

alone.

What we do: Minutes of walking per day at age 50 is associated

with less dementia risk and better brain volumes.Borenstein A et al.

What we do, the habits we maintain moment to moment, day to day, week to week, month to month, year to year changes us.

What we do:

Erickson K et al. The influence of aerobic exercise intervention on Brain Volume in late adulthood. F1-0301, July 2012, AAIC.

120 older adults without dementia were randomized

to moderate walking or stretching/toning for 1 year.

In walkers but not stretchers:

MRI scans show increased hippocampal size.

Blood showed higher levels of Brain Derived

Neurotrophic Factor (BDNF).

What we do:

155 community dwelling Vancouver women 65-75 yrs. MMSE >24, capable of exercise, no resistance exercise in 6 mo, not depressed

Randomized to RT, Resistance Training 1X or 2x/wk, or 2x/wkBalance & Toning, BT--12 mos. 70-71% compliance rate for RT; 62% for BT.

Muscle power was stronger in RT group. (-16% power in BT)

MSK pain reported in 30% RT & 9.5 % BT. NO Pain reports after 4 wks.

RT was more efficacious than BT in improving attention and executive function. Improvement in both the 1x and 2x per week RT was 11-13% better. (BT – 0.5%)

Liu-Ambrose, Nagamatsu etal. Arch Int Med 2010. O1-08-06 AAIC 2012.

Resistance training & executive function: a 12-mo randomized controlled trial(†Refining exercise prescription to promote executive function in older adults)

What we do: (Liu-Ambrose etal CGS 2015)

There’s even more learning from this study!

RT compared with BAT had significantly reduced white

matter Hyperintensity (WMH) on MRI.

Reduced WMH progression is associated with maintenance

of gait speed (p=.04) & improved Stroop performance

(p=.06)

Aside commentary:

Nadkarmi etal JAGS 2013: Type of training of those >65 with

gait impairment matters. Task-oriented (n=23) with training

on timing & coordination resulted in gait speed change

independent of WMH; whereas walking, endurance, balance &

strength (WEBS) had smaller gait speed gains.

What we do:

Nagamatsu L et al. Resistance Training promotes cognitive functions and functional plasticity in senior women with probable mild cognitive impairment (MCI): a 6 mos RCT. F1-03-02, AAIC July 2012.

The EXCEL trial: Exercise for Cognition and Everyday Living.

N=86, 70-80 year old women with MCI were randomized to 6 mos of 2X weekly resistance training--RT (n=28), aerobic training--AT(n=30), or toning (n= 28).

RT improved on important tests of cognition (p=0.04 and <0.03).

AT improved on balance, mobility, and cardiovascular capacity (p=0.04).

The changes in exerciser cognition were evident in functional changes in MRI scans.

What we do:

Barnes et al. JAMA 2013. The Mental Activity and eXercise (MAX) trial: a RCT to enhance cognitive function in older adults.

126 inactive community living older adults, ave age 73.4, with memory complaints.

All subjects had physical exercise & brain exercise. What varied was the type. Stretching & tone vs aerobic, 1 hour 3x/wk. Mental activity was intensive computer vs educational DVDs, 1 hour 3x/wk. 12 week program.

All groups improved p<0.001.

There was no difference between groups, p= 0.26.

Impression: what matters most is to be active!

What we do:

Vreugdenhil et al. Scand J Caring Sci 2012. A community-based exercise programme to improve functional ability in PWD: a RCT.

40 persons with AD (ave age 74.1, MMSE 22) & their carer were

randomized to exercise vs usual care for 4 months.

Carer-lead daily home based walking & exercise program.

The MMSE improved by 2.6 points, p<0.001. !!!

Improvement on functional tasks, p=0.007.

Faster walking and transferring speed, p=0.004.

Literature review: Littbrand et al. Applicability & Effects of

Physical Exercise on Physical& Cognitive Function & ADL Among

People with Dementia. AJPMR 2011;90(6): 495-518.

What we do:Effects of the Finnish AD Exercise Trial: (FINALEX): a Randomized Control Trial Pitkala et al JAMA 2013.

210 home dwelling AD patients with caregiver.

Outcomes: Functional Independence Measure (FIM), physical performance measure, and social and health costs.

3 groups followed for 1 year: GE, group exercise 2X/week—4-hour sessions--1 hour training. HE, home exercise 2X/week—1-hour training. CG, Control group—usual care.

Deterioration was fastest in the control group (~2X as fast) p=0.015.

Both GE and HE had fewer falls than CG.

Costs trended less in the HE group vs CG.

Costs were less in the GE vs CG, p=0.03.

Lifestyle Interventions & Independence

for Elders (LIFE study) Sink et al JAMA

2015

RCT, single blind, 24 mo,1635 community living seniors, age 70-89, USA.

Inclusion/exclusion criteria: No dementia (3MSE cutoff adjusted for education

& ethnicity), co-morbidity, walk 400m w/o Ax < 15 min, at risk for mobility

dependency.

Participants: Mean BMI= 30, ~28% DM, 20% gluc. Intol., ~7% stroke, HTN

75%, CVD ~29%, ~66% college ed; walking speed = 0.83 m/s. At baseline,

ave. walking & strength training= 75, PA; 87, HE, min/wk.

Intervention: 2 group sessions/wk & home 3-4 X/week; goal 30 min walk, 10

min of leg resistance training & 10 min of balance training.

71% compliance at PA sessions; self report increase in activity 130 min/wk,

PA; 31 min/wk, HE .

Conclusion: Among sedentary older adults a 24 mo moderate intensity PA program compared with health education did not result in improvements in global or domain-specific cognitive function.

BUT!!

Those > 80 (n=307) & those with

poorer baseline physical

performance (n=328) had

improvement in executive function

compared to HE group. (p=0.01)

Lifestyle Interventions &

Independence for Elders (LIFE study)Sink et al JAMA 2015

What we do:

Is it ever too late to start walking? NO!!

Winchester J et al. Arch of Gerontol and Ger 2013.

Walking stabilizes cognitive functioning in Alzheimer

Disease.

Sedentary persons with AD declined over 1 year.

Those who had >2 hours per week of physical activity

improved.

Those with ~1 hours/week of activity plateaued.

Cognitive scores of walkers and sedentary over time

Winchester J et al Archives of Gerontology and Geriatrics 2013

Kemoun et al. 2010

Van De Winckel et al. 2004

Venturelli et al. 2011

Vreugdenhil et al. 2012

Study or Subgroup

Figure 1--A forest plot of the meta-analysis of RCT studies that have measured global cognitive outcome. Exercise interventions were found to have a positive effect on global cognitive outcome.Farina, N. et al. International Psychogeriatrics 2014, 26:1 9-18

Meta-analysis of Exercise interventions to enhance cognition. Farina et al 2014.

What we

do:

Carcel et al. Ballroom dancing improves memory in older adults. P1-101,

AAIC 2012.

Tai Chi studies: Chu, AAIC 2014 ; Wu Y, J of Sport & Health Science

2013.(The effects of Tai Chi exercise on cognitive function in older adults: A

meta-analysis)

Planned FIT-AD trial (Yu 2014) will use cycling as intervention.

Neville & Henwood 2014. Swimming improves behaviour & well-being in

persons with dementia.

BOTTOM LINE: MOVE! DO SOMETHING!

What we do:Park J et al. JAGS 2017; 65:592-97

Chair yoga: an RCT of Sit and Fit versus Health

Education Program (HEP)

131 adults over age 65 with lower limb arthritis

8 week intervention, 2x/wk, for 45 min

The yoga group:

Had less pain, less interference of pain in activities,

less fatigue, and improved gait speed

What we do: Play mahjong! Cheng, Int J Psychiatry 2006

62 persons with Alzheimer’s (MMSE < 24)

Played 2-4X per week.

Improved MMSE, digit span, and verbal memory

Play Chess! Don’t watch TV! Wang 2006 “Leisure Activity & Risk of cognitive Impairment: The Chongqing Aging Study” Mind sport reduced the risk of cognitive impairment

TV watching was associated with increased risk!

Verghese 2006—higher participation in leisure activity is associate with lower risk of mild cognitive impairment in those >75 yr old.

What we do: Art

Storytelling, Reminiscence

Crafts

Theatre, drama

1. McGreevy J, Nurs Older People 2016

2. George DR, Dementia 2014

3. Pollanen SH, Occup Ther Health Care 2014

What we doBarengo NC et al. Leisure-time PA (LTPA)

Reduces Total & Cardiovascular Mortality & Cardiovascular Disease Incidence in Older Adults. JAGS 2017; 65: 504-10.

Finnish men & women, age 65-74, N=2456 followed 1997-2007.

Baseline LTPA reduces risk of CV & total mortality independently of known CV risks.

LTPA is dose dependent.

What we do:

What we do:

Head D et al. 2012. Exercise Engagement as a Moderator of the Effects of the APOE Genotype on Amyloid Deposition.

Amyloid binding in the brain is one marker associated with AD as is level of Cerebrospinal Fluid Markers.

CSF samples taken, Amyloid-PET scans done, self-reported 10-year exercise history, subjects were “genotyped.” Results controlled for age, sex, education, medical diseases. 201 total subjects. 168 had PET scans; 165 had CSF sampling.

201 cognitively normal, age 45-88, 108 ApoE carriers.

ApoE carriers who are exercisers had a marked protection from Amyloid deposition, p<0.001.

0

0.05

0.1

0.15

0.2

0.25

Nonexercisers

ApoE4 -

(n = 86)

Exercisers

ApoE4 -

(n=25)

Nonexercisers

ApoE4 +

(n = 39)

Exercisers

ApoE4 +

(n = 13)

Am

ylo

id

Bin

din

g

Head D et al. 2012. Exercise Engagement as a Moderator of the Effects of the APOE Genotype on Amyloid Deposition.

Association between Amyloid status & exercise engagement

What we do:

Wang H-X. An Active Lifestyle Postpones Dementia onset by More than One Year in very Old Adults. O1-08-

01 AAIC 2012.

The age of onset for dementia is later for persons with

higher levels of mental, physical, or social activity

(p=0.001).

~1400 people, mean age of 80, followed for 9 yrs.

Of the 388 who developed dementia, those who were

inactive were 17 months younger than their active

counterpart.

Case : Mrs. Toula

Sectamauve Mrs. TS is a 75 yo homemaker with fibromyalgia,

macular degeneration, OA, Depression/anxiety, walks with a cane, lives alone, says she is lonely. She is referred by her doctor to the Kiwanis for “activation.”

No home help; independent IADLS/ADLS. 1 fall with ER visit this year.

“I exercise walking in the Grocery store.”

Strategies? Barriers? Motivators?

Case : Mrs. Toula

Sectamauve What is her personal history of hobbies, community

engagement?

What is her personality?

What are her personal goals? (common ground)

What are her fears for the future?

Now, what are your strategies?

Summary: There is growing strong evidence that a Mediterranean

Diet prevents dementia and vascular disease.

Exercise is a strong modulator of cognition with a

protective effect.

Meditation is a health promotion practice that has a

multimodal effect on brain health.

Learning and doing new things is associated with

brain health.

What you do at RTs matters!!!

It’s never too late!

References:• Barnes et al. The Mental Activity and eXercise (MAX) trial: a RCT to enhance cognitive

function in older adults. JAMA 2013; 173(9): 797-804..• Beking K and Vieira A. Flavenoid intake & disability-adjusted life years due to AD and

related dementias: a population-based study involving 23 developed countries. Public Health Nutrition 2010; 13(9): 1403-9.

• Borenstein A et al. Minutes of Walking per day at ate 50 is associated with Dementia risk. P1-098. AAIC 2012.

• Buchman A et al. Association Between Late-life Social Activity & Motor Decline in Older Adults. Arch Intern Med 2009; 169(12): 1139-46.

• Cao C. et al. High Blood Caffeine Levels in Older Adults Linked to Avoidance of AD. J Alz Disease 2012; 29: 1-14.

• Carcel C et al. Can ballroon dancing make you smarter: An investigation of its relationship with hippocampal volume and memory performance in older adults. P1-

101, AAIC 2012.• Carey AN et al. The beneficial effects of tree nuts on the aging brain. Nutrition &

Aging 2012; 1(1): 55-67.• Cheng S-T et al. Mental & Physical Activities Delay Cognitive Declinie in Older

Persons with Dementia. Am J Ger Soc Feb 2013.• Erickson K et al. The influence of aerobic exercise intervention on Brain Volume in

late adulthood. F1-0301, AAIC 2012.• Estruch et al.Mediterranean Diet & Cardiovascular Prevention. NEJM 2013;

368(14):1279-1290.• Fallah N et al. Refining exercise prescription to promote executive function in older

adults using multistate transition modeling. O1-08-06 AAIC 2012.

Frautschy S et al. Impact of diet and exercise on development of tau pathology. O2-

05-01 AAIC 2012.

Helcer J et al. Cognitive Behaviour Therapy to Combat Hopelessness and Low Self

Efficacy in AD. P2-325, AAIC 2012

Head D. et al. Exercise Engagement as a Moderator of the Effects of APOE Genotype

on Amyloid Deposition. Arch Neurol 2102;69(5):636-643.

Khalsa, D. Meditation & AD Prevention: the forgotten factor. P1-104. AAIC 2012.

Kraus Nina. Canadian Conference on Dementia, Oct. 2013; Vancouver, BC.

Kraus N. Music Training: an Antidote for Aging? The Hearing Journal 2013;66(3):52.

Kuriyama S. Green Tea consumption & cognitive function: a cross-sectional study

from the Tsurugaya Project 123. Am J Clin Nut 2006;83(2):355-61.

Lamport DJ et al. The effects of flavenoid & other polyphenol consumption on

cognitive performance: a systematic review of human experimental & epidemiological

studies. Nutr & Aging 2012;1(1):5-25.

Lautenschlager N. Can participation in Mental and Physical Activity Protect Cognition

in Old Age? JAMA 2013;173(9):805-6.

References: Lindsay J et al. Risk Factors for AD: A prospective Analysis from the Canadian Study on Health

and Aging. Am J of Epi 2002;156(5):445-453.

Lopez J e tal. Spirituality & self-efficacy in dementia family caregiving: trust in God & in yourself. Internat Psychoger Assoc 2012; 12(24):1943-52.

Littbrand H et al. Applicability & Effects of Phyical Exercise on Physical& Cognitive Function & ADL Among People with Dementia. AJPMR 2011;90(6):495-518.

Liu-Ambrose T et al. Resistance training and executive functions: a 12-month randomized controlled trial. Arch Int Med 2010;170(2):170-8.

Moss A et al. Effects of an 8 week Meditation Program on Mood & Anxiety in Pts with Memory Loss. J Alt M & Compl Med 2012;18(1):48-53.

O’Brien J et al. Long-term consumption of nuts in relation to cognitive function and decline in women. P2-158, AAIC 2012.

Pagnoni G & Cekic M. Age effects on grey matter volume & attentional performance in Zen meditation. Neurbio of Aging 2007;28:1623-27.

Nagamatsu L et al. Resistance Training promotes cognitive functions and functional plasticity in senior women with probable mild cognitive impairment (MCI): a 6 mos RCT. F1-03-02, AAIC 2012.

Nelson P et al. Self-reported Head Injury (HI) and risk of Cognitive impairment & AD type pathology in a Longitudinal AD Center Cohort O5-05-04, AAIC 2013.

References for 2013 talk: Pettersen J. Vitamin D & Verbal fluency: Are higher levels better? P3-141, AAIC 2013.

Pitkala et al Effects of the Finnish AD Exercise Trial: (FINALEX): a Randomized Control Trial. JAMA 2013; 173(10):894-901.

Raglio A et al. Efficancy of Music therapy in the Treatment of Behavioural & Pschiatric Symptoms of Dementia. Alz Dis Assoc Disord 2008; 22(2):158-162.

Rendeiro C et al. Dietary Levels of Pure Flavonoids Improve Spatial Memory Performance & Increase Hippocampal Brain-derived Neurotrophic Factor. Plos One 2013;8(5):1-9.

Rovio S et al. Leisure-time physical activity at midlife and the risk of dementia & AD. The Lancet Neurology 2005;4:705-711.

Scarmeas N et al. Physical Activity, Diet, & Risk of AD. JAMA 2009; 302(6):627-37.

Shah T et al. Cross Training of Auditory and visual Brain Training Software program improves cognition and alters plasma BDNF levels in Healthy older adults. O1-08-03 AAIC 2012.

Sung H-C et al. A preferred music listening intervention to reduce anxiety in older adults with dementia in nursing homes. J Clin Nurs 2010;19:1056-64

Svansdottir HB & Snaedal J. Music therapy in moderate & severe dementia of Alzheimer type: a case-control study. Internat Psychogeriatri Assoc 2006;18(4):613-21.

Tippet W & Rizkalla M. Training the Brain: Can Cognitive Training Alter the Global Effects of Alzheimer Disease? Abstract # O2-01-03. Alzheimer Association International Conference AAIC July 2012.

References: Vreugdenhil et al. A community-based exercise programme to improve

functional ability in people with AD: a RCT. Scand J Caring Sci 2012;26(1):12-

19.

Wang H-X. An Active Lifestyle Postpones Dementia onset by More than One

Year in very Old Adults. O1-08-01 AAIC 2012.

Westerlund O et al. Relationship Between Marital & Parental Status and Risk

of Dementia & AD. P3-204, AAIC 2013.

Willis et al. Long-term effects of cognitive training on everyday functional

outcomes in community JAMA 2006; 296(23)):2805-14.

Winchester J et al. Arch of Gerontol & Ger 2013;56:96-103.

Wu Y et al. The effects of Tai Chi exercise on cognitive function in older adults:

A meta-analysis. J Sport & Health Sci 2013; Sept 28: on-line publication.

For 2015 talk:

What we do: Diet and Exercise: AD mouse model.

Frautschy S et al. Impact of diet and exercise on development of tau pathology. O2-05-01 July 2012 AAIC.

Curcumin (anti-inflammatory), Omega-3 FA, α-lipoic acid (anti-oxidant) and voluntary exercise reduced “tau pathology” synergistically.