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The hippocampus & cortex are areas of brain affected by AD

“Hippocampus” means

“seahorse”, it is important for

spatial memory*.

2

*Maguire J. Neurosci. 1997 ©p

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Neurons store information

Neurons communicate with

each other through synapses

In AD, synaptic connections

are lost

Then dendrite “branches” are

lost

Eventually, the neurons dies

Other cell types are involved:

Oligodendricytes

Astrocytes

Microglia

Endothelia 3

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AD brain tissue has

microscopic Ab plaques &

Neurofibrillary tangles

The brain shrinks in

advanced AD

Hippocampus can virtually

disappear

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There are currently ~

3-4 million people in

the US with AD.

The available drugs

provide only

temporary

symptomatic relief.

New approaches

are necessary.

5 There is greater freedom to explore new

ideas using a pharmaceutical model in an

academic setting. ©p

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We identified a

compound “F03”

that increases

pro-cognitive

sAPPa.

F03* is now in

clinical trials for

Mild Cognitive

Impairment

(MCI)

“Anti-AD”

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*Spilman Brain Res. 2014

We also have an improved version of F03 moving

toward clinical trials!

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Early & accurate

diagnosis &

treatment are

key.

More than one

intervention will

likely be

necessary.

Drugs are more

likely to work if

health is

improved.

Early diagnosis of

cognitive

impairment

Healthstyle

support

“Multimodal

treatment”

7

See a description of Dr. Dale E. Bredesen’s MEND in Impact Aging

(www.impactaging.com) Sept 2014 & Aug 2015

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Intake

Scientific/biochemical

bases for how what/when

we eat & how

medications we take

affect cognition are

presented.

The importance of social

interaction, intellectual

challenges, exercise, &

general health to the

preservation of cognition

are discussed.

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Exercise improves

cognitive function!

Use body & mind together

by dancing, playing tennis

or golf, or by yoga practice

Strength building is equally

important – it increases

Brain-Derived Neurotrophic

Factor (BDNF)*

9 *Nascimento Curr. Alz. Dis. Res. 2014 ©pspilman2015

Walking/hiking combined

with a navigational*

challenge is excellent for

spatial memory.

Walk with a friend.

Take a break from “Nav”

apps – look at a map!

Try new routes, and re-enforce with

return trips.

*Brown, J. Neurosci. 2014

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Reduced estrogen/androgen associated

with decreased bone density.

Have calcium levels measured,

supplement if necessary

Have vitamin D3 levels measured

Strength training increases bone density.

Sunscreen may reduce vitamin D

conversion to active form

There is correlation between bone density &

cognitive decline*.

*Zhou, Curr Alzheimer Res. 2014

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Brain debris,

including Ab, are

cleared during sleep.

Memories are

consolidated during

sleep.

Lack of sleep impairs

cognition* &

increases disease.

Keep room dark &

cool.

Avoid chronic use of sleep

aids such as zolpidem** &

diphenhydramine# if possible.

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*Kreutzmann, Neuroscience. 2015; **Levy Expert Rev Clin Pharmacol. 2014;

#Chen, Acta Pharmacol Sin. 2001 ©p

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Apnea (cessation of

breathing while sleeping)

leads to damage to the

brain*.

Apnea prevents restorative

sleep & can cause vascular

disease.

It is caused by chronic

respiratory disease,

inflammation, orthopedic or

neurological issues.

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*Arli, Appl Neuropsychol Adult. 2014

A CPAP mask can help.

Also address causative

health issues, like obesity.

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Chronic stress increases tau

phosphorylation & tangles.

Exercise & sleep relieve stress.

Yoga & daily meditation are

also good - meditation

preserves gray matter

(neurons).

Pets, comedy, & music all

reduce stress.

Mindful-Based Stress

Reduction increases

“functional connectivity.*”

Some “stress” is good.

*Wells, Neurosci. Lett. 2014 ©

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Creating music stimulates brain areas

important for neurogenesis (new cell

formation)

Learn to play an instrument…

…even your own voice

Music triggers memory

A great book: Oliver Sacks’

Musicophilia A great documentary:

Alive Inside - Music & Memory

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*Cuddy Annal NY Acad Sci 2015

Humor, comedy & laughter can

effectively relieve stress.

Social laughter is correlated with an

elevated pain threshold”.*

A great book: Norman Cousin’s

Anatomy of an illness. Laughter can relieve stress &

depression.

Laughter Improves short-term memory.

Kawaii (cuteness) improves focus.

*Dunbar et al Proc Biol Sci. 2012 Mar 22;279(1731):1161-7

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Loss of sensory input impairs

cognition*.

Hearing – have it tested, get hearing

aids.

Have aldosterone levels determined &

corrected.

Olfaction (smell) – focus on olfactory

experiences.

Sight - Keep eyeglass prescriptions up-

to-date.

Taste – add variety!

Expand all sensory experiences. 17

*Bush. Ear Hear. 2015 ©p

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Use all of your cognitive abilities.

Try something new.

Be a teacher.

Discuss ideas.

Master a new skill.

Focus intently on a new subject.

Consider video* or brain training

software or games to follow

performance.

Why are we expected to learn less as

we age?

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*Kuhn Mol. Psychiatry 2014 ©p

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Give yourself a sense of purpose

beyond career.

Volunteer using your skill set.

Interact with & contribute to your

community*.

Maintain inter-generational

relationships.

Pursue spirituality, whatever that

means to you.

Help your friends to do this too!

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*Paganini-Hill Alz. Dis & Assoc. Dis. 2015 ©p

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X

X

X

Share activities with friends & family.

Be a “good” host providing healthy

choices.

Suggest a walk after a meal.

The holidays do not have to be

unhealthy!

Friends & spouses share similar

“healthstyles”.*

Share your knowledge.

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*Christakis N Engl J Med. 2007 ©p

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? Not

Accurate Diagnosis is Critical

Diagnostics include:

Computer-assisted tomography (CAT) for structural

abnormalities

Positron emission tomography (PET) for glucose use

& amyloid imaging

Function magnetic resonance (fMRI) for blood flow

Tests of cognitive function

Other causes of memory loss:

Depression, infection, multiple sclerosis, low B12,

hypothyroidism, medication interactions, tumor

Not all dementia is AD:

Vascular dementia, Parkinson’s/Lewy Body

disease, frontotemporal dementia

Memory & Aging Centers at UCSF/Stanford

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You can donate to the Buck Institute.

You can donate to a specific laboratory.

You can donate to the Drug Discovery lab as

an individual or as an action group.

Meet with our team to discuss “Venture

Philantropy” – your contribution might be a

better investment than you can imagine!

Get updated reports and presentations with

your support.

www.theBuck.org

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2. Spilman P, Descamps O, Gorostiza O, Peters-Libeu C, Poksay KS, Matalis A, Campagna J, Patent A, Rao R, John V, Bredesen DE. The multi-functional drug tropisetron binds APP and

normalizes cognition in a murine Alzheimer's model. Brain Res. 2014 Mar 10;1551:25-44.

3. Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY). 2014 Sep;6(9):707-17.

4. Nascimento CM, Pereira JR, de Andrade LP, Garuffi M, Talib LL, Forlenza OV, Cancela JM, Cominetti MR, Stella F. Physical exercise in MCI elderly promotes reduction of pro-

inflammatory cytokines and improvements on cognition and BDNF peripheral levels. Curr

Alzheimer Res. 2014;11(8):799-805.

5. Brown TI, Whiteman AS, Aselcioglu I, Stern CE. Structural differences in hippocampal and prefrontal gray matter volume support flexible context-dependent navigation ability. J

Neurosci. 2014 Feb 5;34(6):2314-20.

6. Zhou R, Zhou H, Rui L, Xu J. Bone loss and osteoporosis are associated with conversion from mild cognitive impairment to Alzheimer's disease. Curr Alzheimer Res. 2014;11(7):706

7. Kreutzmann J, Havekes R, Abel T, Meerlo P. Sleep deprivation and hippocampal vulnerability: changes in neuronal plasticity, neurogenesis and cognitive function.

Neuroscience. 2015 Apr 29.

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9. Chen Z, Chen JQ, Kamei C. Effect of H1-antagonists on spatial memory deficit evaluated by 8-arm radial maze in rats. Acta Pharmacol Sin. 2001 Jul;22(7):609-13.

10. Arli B, Bilen S, Titiz AP, Ulusoy EK, Mungan S, Gurkas E, Oztekin ZN, Ozcan M, Ak F. Comparison of Cognitive Functions Between Obstructive Sleep Apnea Syndrome and

Simple Snoring Patients: OSAS May Be a Modifiable Risk Factor for Cognitive Decline. Appl

Neuropsychol Adult. 2014 Dec 12:1-5.

11. Wells RE, Yeh GY, Kerr CE, Wolkin J, Davis RB, Tan Y, Spaeth R, Wall RB, Walsh J, Kaptchuk TJ, Press D, Phillips RS, Kong J. Meditation's impact on default mode network and

hippocampus in mild cognitive impairment: a pilot study. Neurosci Lett. 2013 Nov 27;556:15

12. Bush AL, Lister JJ, Lin FR, Betz J, Edwards JD. Peripheral Hearing and Cognition: Evidence From the Staying Keen in Later Life (SKILL) Study. Ear Hear. 2015 Jan 13.

13. Cuddy LL, Sikka R, Vanstone A. Preservation of musical memory and engagement in healthy aging and Alzheimer's disease. Ann N Y Acad Sci. 2015 Mar;1337:223-31.

14. Kühn S, Gleich T, Lorenz RC, Lindenberger U, Gallinat J. Playing Super Mario induces structural brain plasticity: gray matter changes resulting from training with a commercial

video game. Mol Psychiatry. 2014 Feb;19(2):265-71.

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©pspilman2015