Practices and Investigational Approaches to Symptom Management

ADC Spring Meeting 2015 Clinical Core Leaders Meeting April 18, 2015 , Washington, DC

What should we do until we have a prevention for AD? Practices and Investigational Approaches to Symptom Management

FDG PET Tau PET Amyloid PET Association of AD Pathology with Cognition

in Rush ROS and MAP* *Adj for age, sex, educ z ) Global Cognition (

Plaque & Tangle Composite (z) Some Successful Treatments for AD* Tg2576 Dihydropyridine antihypertensives PF-04447943 (PDE9A-I) pS396/404 Tau vaccine 4-O-methylhonokiol Paeonia suffruticosa 5-lipooxygenase (AAV) Dihydromyricetin (flavanoid/GABA) Sodium selenate PF-04447943 (PDE9A-I) a-lipoic acid (dietary) DP-155 (indometacin lecithin derivative) T-817MA (neuroprotectant) PF-3084014 (g-secretase Ab oral vaccine (salmonella) Dihydropyridine antihypertensives Tau immunization Abeta-Hsp70 active immunization DP-155 (indometacin lecithin derivative) Phenylbutyrate (HDAC-I) Uridine prodrug Activated Protein C Early cognitive stimulation Phytic acid EGCG (green tea) + fish oil PN401 (uridine) Adipose mesenchymal stem cells P301L Aged garlic extract Erythropoietin Pomegranate 3xTg (APP/PS1/Tau ) AM580 (RARa) Exrercise, voluntary Propanolol Aminohydantoins (BACE1) Figs from Oman Quadrivalent foldable Ab(1-15)(AAV) 2-Deoxy-D-glucose Aminoimidazoles (BACE1i) Flurbiprofen R-flurbiprofen Allopregnenalone Amniotic stem cells (TGF-b) Folate (homocystein normalization) Rosiglitazone Apomorphine Chinese celery extract L-NBP) Anesthesia (isoflurane, propofol, others) Gastrodin Sildenafil Dantrolene Antalamin (CRF1) Ginkgo biloba SK-PC-B70M Dihydrotestosterone (DHT) Anti-Ab antibody (AAV) Ginsenoside (Ginseng) SPI-1865 (g-secretase -I) APP antisense oligonucleotide TAK-070 (BACE1) Dimebon Grapeseed polyphenols H2S APP b-secretase cleavage site antiboy GRL-8234 (b-secretase inhib) TO901317 (LXR agonist) AS2715348 (g-Secretase modulator) Huperzine A (AcheI) GSI-953 (Begacestat, g-secretas)e Triflusal AZ-4217 (BACE-I) Ibuprofen Huprine X Turmeric extract (optimized) Bacailein (flavanoid/GABA) APP b-secretase site antibody IAC (bis(1-hydroxy-2,2,6,6-tetramethyl- Umbilical cord blood cells BAY73-6691 (PDE9A-I) Luprolide 4-piperidinyl) decantionat Valsartan Memantine BC05 (Ab42(43) C-term antibody) Vitamin D3 BDE-209 IGF2/1 (AAV) Mitoquinone (Redox) Walnuts BDNF (SVV) JNJ-40418677 (g-secr modulator) NDP-a-MSH X11beta BMS-433796 (g-secreatse inhibitor) Magnolia extract Neuropep-1 C5aR antagonist Melatonin Yokukansan phyto-b-SERM Caffeoylquinic acid Memapsin-2 (b-secrease immunization) Zinc (p.o.) Pioglitizone Calorie restriction Minocycline R-flurbiprofen (NSAID) Captopril (ACE-I) MRK-560 (g-secretase inhib) P301L S14G-HN Humanin Cerebrolysin NDP-a-MSH (Melanocortin) Tau Tg SC-560 (COX-1 inhibitor) Spirolides CHF5022 (g-secretase inhib) Neprilysin 17-AAG Thalidomide (TNFa) CHF5074 (NSAID/g-secretase-I) Neuritin (AAV) Deferoxamine Voluntary running Ciproxifan (H3R antag) Nicotinamide riboside (PPARg) Grape seed polyphenolic extract Zileuton COX2 inhibitor NNC-26-9100 (somatostatin) Immunization (active) Dates from Oman oAb immunization Lithium Deferoxamine Obovatol Methylene blue Dihydromyricetin (flavanoid/GABA) Paeonia suffruticosa * in mice, 2005-2014 An Example of Anti-Amyloid Immunotherapy for AD

Pre-Clinical PBS Control Phase 2

PabAβ1-42 Treatment

Adapted from Bard et al, Nature Medicine, 2000 Phase 3 Association of AD Pathology with Cognition

in Rush ROS and MAP* *Adj for age, sex, educ z ) Global Cognition (

Plaque & Tangle Composite (z) Association of AD Pathology with Cognition

in Rush ROS and MAP* *Adj for age, sex, educ z ) Global Cognition (

Plaque & Tangle Composite (z) ADC Spring Meeting 2015 Clinical Core Leaders Meeting April 18, 2015 , Washington, DC

What should we do until we have a prevention for AD? Practices and Investigational Approaches to Symptom Management

Steven E. Arnold, M.D., Introduction Martin R. Farlow, MD: Pharmacological Approaches for Cognition Laura D. Baker, PhD: Exercise and Non-Pharmacological Approaches Constantine G. Lyketsos, MD: MIND & Community Dementia Care Murray A. Raskind, MD: Prazosin for Agitation & Drug Re-Purposing We are all looking for the effortless magic pill for dementia but functional abilities in aging and dementia are complex and not jest related to cognition but also physical conditioning and its complex relationship to brain functioning, psychosocial support and psychiatric status. So the program this afternoon is a little scientific update on each of these areas.