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The hippocampus & cortex are areas of brain affected by AD “Hippocampus” means “seahorse”It is important for spatial memory*

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*Maguire J. Neurosci. 1997©pspilman2015

Neuron lose synaptic connections, then dendrite branches & eventually die in AD.

Other cell types are involved:

astrocytesoligodendricytesmicrogliaendothelia

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AD brain tissue has microscopic Aβ plaques & neurofibrillary tangles of p-tau

The brain shrinks in advanced AD

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We identified a compound that increases in pro-cognitive sAPPα.

DDL110* is now moving to clinical trials for Mild Cognitive Impairment (MCI)& AD

“Anti-AD”

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*Spilman Brain Res. 2014©pspilman2015

Early 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

Healthstylesupport

“Multimodal treatment”

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©pspilman2015

IntakeScientific/biochemical bases for how what/when we eat & how medications we take affect cognition are presented.

OutputThe importance of social interaction, intellectual challenges, exercise, and general health to the preservation of cognition are discussed.

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Journal of Neurology Neurosurgery & Psychiatry. 2015

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

*Brown, J. Neurosci. 2014

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CAD may be silent early on, but result in TIA or stroke. Signs/symptoms:Sudden numbness or weaknessSudden trouble speaking and understandingSudden trouble seeing in one or both eyesSudden dizziness or loss of balanceSudden, severe headache with no known cause

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From

Visu

al.ly

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*Christakis N Engl J Med. 2007 ©pspilman2015

Support the Health of Others

?Not

Accurate Diagnosis is Critical

Diagnostics include:

Computer-assisted tomography (CAT) for structural abnormalitiesPositron emission tomography (PET) for glucose use & amyloid imagingFunction magnetic resonance (fMRI) for blood flowTests 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

UCLA Memory Disorders Clinic (310) 794-6039©pspilman2015

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Maguire EA, Frackowiak RS, Frith CD. Recalling routes around london: activation of the right hippocampus in taxi drivers. J Neurosci. 1997 Sep 15;17(18):7103-10.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.Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY). 2014 Sep;6(9):707-17.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. CurrAlzheimer Res. 2014;11(8):799-805. 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.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):706Cuddy 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.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.Paganini-Hill A, Kawas CH, Corrada MM. Lifestyle Factors and Dementia in the Oldest-old: The 90+ Study. Alzheimer Dis Assoc Disord. 2015 Mar 6. Christakis NA, Fowler JH. The spread of obesity in a large social network over 32 years. N Engl J Med. 2007 Jul 26;357(4):370-9. ©pspilman2015