Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of...
-
Upload
constance-nash -
Category
Documents
-
view
215 -
download
1
Transcript of Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of...
![Page 1: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/1.jpg)
Elephants never get dementedI wonder what drugs they’re
on?
David Greenhouse, MD, CMD
Director of Geriatric Education
USC SoM
![Page 2: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/2.jpg)
![Page 3: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/3.jpg)
Stanley
75 yo male seen in the FPC for f/u As part of geriatric curriculum resident
performs Mini-Cog 3 object recall: moon, dog, watch Clock draw test
Long term memory question Why did Kennedy leave office?
![Page 4: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/4.jpg)
Results
1/3 recall after clock draw distraction
“He was having an affair. He was voted out.”
MMSE 20/30
![Page 5: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/5.jpg)
Diagnosis
After some further testing and talking to family, you make the clinical diagnosis of Alzheimer’s type dementia
![Page 6: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/6.jpg)
4.5 million cases today
45.8
6.8
8.7
11.3
13.2
0
2
4
6
8
10
12
14
2000 2010 2020 2030 2040 2050
Year
Millions
Projected Prevalence of AD3rd most expensive disease, $100 billion
![Page 7: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/7.jpg)
![Page 8: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/8.jpg)
Disease Specific Death Rates
Heart disease Down 3 %
Cancer Down 1 %
CVA Down 2.8 %
Alzhemier’s disease Up 5.8 %
Kidney disease Up 1.4
Septicemia Up 2.6 %
Diabetes Up 0.4 %
Knowable, unintended consequences
We all have to die from something. As long as we make gains in treatment of Cardiovascular disease, other diseases will become more prevalent.
![Page 9: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/9.jpg)
Fantastic Voyage
![Page 10: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/10.jpg)
A Look Inside
![Page 11: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/11.jpg)
At the synapse
Loss of acetylcholine neurons starting in hippocampus
![Page 12: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/12.jpg)
Plaques at the Cell Membrane Level
Cholesterol modulates APP processing
Cyp46 = 24S-cholesterol hydroxylase
![Page 13: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/13.jpg)
The Tangled Web
Plaques injury kinase activation
Kinases phosphorylates microtuble tau protein forming tangles
![Page 14: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/14.jpg)
Something New Under the Sun Excitotoxicity
Glutamate Major excitatory neurotransmitter for cognition &
learning Glutamate neuronal loss correlates with degree of
dementia
![Page 15: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/15.jpg)
N-Methyl-D-Aspartate forms ion channel for Ca entry Ca intracellular messenger Inactive receptor blocked by Mg Uncontrolled activation causes cell death
![Page 16: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/16.jpg)
Glutamate in ATD
Glutamate transporter down regulated Increased synaptic glutamate activity
Glutamate promotes APP synthesis β-amyloid inhibits re-uptake of glutamate and
enhances glutamate release Increased NMDA receptor activity increases
phosphorlyation of tau protein
![Page 17: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/17.jpg)
The Stroke Connection
Cognitive performance decreased in those with stroke risk factors Abstract reasoning, visualspatial memory, visual
organization, concentration most affected Snowdon Nun Study
![Page 18: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/18.jpg)
Glutamate & Stroke
![Page 19: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/19.jpg)
Pathophysiologic model
Glutamate
β-AmyloidNeurofibrillary
TangleExcitotoxicity
Cell death
Dementia
Inflammation
![Page 20: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/20.jpg)
Do we have anything to offer?
![Page 21: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/21.jpg)
Non-pharmacologic Strategies
Mental exercises Higher education Physical activity Social activity Diet (fish, low cholesterol)
Think Medical School
![Page 22: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/22.jpg)
Pharmacologic Treatments
Anti-inflammatory agents: NSAIDs Estrogen replacement Antioxidants: vitamin E, selegiline Ginkgo biloba Statins Control vascular risk factors Acetylcholinesterase inhibitors NMDA-receptor antagonists
![Page 23: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/23.jpg)
Anti-Inflammatory Drugs
Observational/epidemiological studies NSIADs associated with reduced risk
Clinical trials Failed to show benefit of prednisone, NSAID,
COX-2
Aisen PS, JAMA 6/4/03; 289; 2819-26
![Page 24: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/24.jpg)
Women’s Health Initiative
Women’s Health Initiative Memory Trial Hazard ratio of 2.05 for probable dementia
1.89 % on E+P vs 0.9% on placebo 12.5 % E+P vs 4.8 % on placebo VCI 50.0 % E+P vs 57.1 on placebo ATD
Yes, more women who developed dementia on placebo developed ATD
No protection for Minimum Cognitive Impairment
Shumaker JAMA 2003; 289: 2651
![Page 25: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/25.jpg)
Vitamin E
Selegiline 5 mg bid or Vitamin E 2000 IU qd Primary outcome: time to death,
institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia
Vit E (670 d) >selegiline (655) >both (585) >placebo (440)
Did not reach statistical significance Cochrane review: insufficient evidence
Sano M, NEJM 1997; 336:1216
![Page 26: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/26.jpg)
This Just In
4740 respondents regarding use of multivitamins, Vit E, Vit C and B-complex
Only people taking combination of Vit E & C had statistically significant protection (HR 0.36) Vit E 1,000 IU and Vit C 500-1,000 mg
Other studies have found reduction in vascular dementia with combination
Zandi, P. Arch Neurol 61 (1): 82-88
![Page 27: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/27.jpg)
Ginkgo biloba
Ginkgo 40 mg PO tid for 6-12 months in mild-moderate dementia
Ginkgo stabilized cognition Serious side effects: coma, bleeding, seizure
LeBars PL JAMA 1997; 278: 1327
![Page 28: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/28.jpg)
Statins
HERS reduced TC and LDL resulted in 50 % decrease in dementia
Epidemiologic studies: Statins decrease risk of AD Jick, Lancet, 30 % reduction in dementia Wolozin, Arch Neuro, 60 % reduction Hajjar statin users had unchanged or improved
MMSE (OR 2.81) Statins decrease β-amyloid deposition
![Page 29: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/29.jpg)
AChEI therapy
Difference in titration, mechanisms of action and metabolism
All have benefits on cognition, behaviors and activities of daily living
Most studied class of medications for ATD Neurostabilizers/neuroprotectors
![Page 30: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/30.jpg)
Donepezil (Aricept)
Introduced 1997; Reversible inhibitor AChE; piperidine
No heptatoxicity Highly protein bound = long half life
Once daily dosing Simple titration
Cytochrome P450 system Long term may up-regulate levels of AChE in CSF
leading to decline in efficacy Least GI side effects
![Page 31: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/31.jpg)
Rivastigmine (Exelon)
Slowly reversible inhibitor of AChE and BuChE; G1 AChE selective (found in hippocampus and
cerebral cortex) Metabolized by target enzymes; not P450
Low protein binding, bid dosing More complicated titration No up-regulation reported Greatest GI side effects
![Page 32: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/32.jpg)
Galantamine (Reminyl)
Phenanthrere from Daffodil stamen Low protein binding, BID dosing More complicated titration Inhibits AChE & modulates nicotinic receptors P450 metabolism Metabolite, sanguinine, 3x power of parent
compound Intermediate GI side effects
![Page 33: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/33.jpg)
AChEI long term benefits
ADAS cog maintained above baseline
Reference
Donepezil (Aricept)
39 wk Rogers, 1998
Rivastigmine (Exelon)
38 wk Farlow, 2000
Galantamine (Reminyl)
52 wk Rasking, 2000
![Page 34: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/34.jpg)
Head to Head Trials
The Evidence is Lacking
MMSE mixed differed
End points different
![Page 35: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/35.jpg)
Rivastigmine v Donepezil
12 week trial, 111 patients, mild to moderate disease
Donepezil better tolerated Similar cognitive and functional outcomes
Too short to really titrate rivastigmine to most effective dosing
Wilkinson DG. Int J Clinic Pract Jul 02; 56(6): 441
![Page 36: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/36.jpg)
Galantamine vs. Donepezil
12 week trial Donepezil better on cognitive and functional
measures Short term and galantamine requires slower
titration to maximize dosing
![Page 37: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/37.jpg)
Galantamine vs Donepezil
Rater blinded, randomized, 12 month, open label, parallel group comparison Galantamine 8 – 24 mg/d Donepezil 5 – 10 mg/d
MMSE remained above baseline for 11 months for galantamine v 6 months for donepezil
No difference in functional measures
McKeith, I Neurology 2003; 60 Suppl 5 A 141
![Page 38: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/38.jpg)
Several years later
Stanley has remained remarkably stable since starting an ACHeI.
On this f/u visit, his daughter relates more forgetfulness and decreased abilities
MMSE 12/30 Daughter “Should we continue the
medication? Do we have any other options?”
![Page 39: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/39.jpg)
New Kid on the Block
![Page 40: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/40.jpg)
Namenda (memantine)
NMDA receptor antagonist
Studies focus on function
Oral, 100 % bioavailable
Minimal metabolism with 57-82 % eliminated unchanged in urine
Does not inhibit P-450
![Page 41: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/41.jpg)
NamendaStabilized at baselinefor 12 weeks. Always above placebo
![Page 42: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/42.jpg)
Namenda dosing
Week 1 5 mg once daily
Week 2 5 mg BID
Week 3 10 mg qam & 5 mg qpm
Week 4, Maintenance 10 mg BID
![Page 43: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/43.jpg)
Add on to Donepezil
404 patient MMSE 5-14 on Donepezil
Randomized to Memantine or placebo in addition to Donepezil
Additional improvements or stabilization in cognition, ADLs, behaviors compared to Donepezil alone
Tariot, P. JAMA Jan 04: 291; 317-324
![Page 44: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/44.jpg)
Time Marches On
MMSE 10/30 Decreased ADLs, incontinent Moved into a Skilled Nursing Home
![Page 45: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/45.jpg)
FAQ
AChEI in late stages Already in Nursing Home One AChEI loses efficacy Other dementias Namenda in early ATD
![Page 46: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/46.jpg)
Donepezil in Advanced Disease
One double blind study and one case report demonstrate efficacy for Donepezil in advanced disease (MMSE 11) Improvements seen in behaviors & ADLs
More long term studies on going My take: use these meds for patients with MMSE >
10 or in those still independent in some ADLs Ambulation, continence, feeding, initiation of activities
Feldman, H. Neurology; 57: 613Tariot, P. JAMDA; July 2003: 216
![Page 47: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/47.jpg)
Other studies in Mod-Severe ATD
Rivastigmine 58 % improvement in irritability, aberrant
behavior, apathy, hallucinations, disruptive night time behavior, agitation, delusions
Galantamine MMSE 12; 6 month trial Cognitive and functional improvements compared
to placebo
Cummings JL. Neurolgy 2000; 54: A469Wilkinson DG Int J Clini Prac 2002; 56(7); 509-14
![Page 48: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/48.jpg)
Donepezil in the Nursing home
208 pt, Mean MMSE 14, frequent behavior problems
24 wk, placebo, blinded study Results
Only improvement seen in agitation/ aggression 61 % concomitant psychotropic
Stabilized MMSE compared to placebo Overall improvement in function in facility
Tariot P. JAGS 2001: 49; 1590-9
![Page 49: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/49.jpg)
Donepezil to maintain ADLs
290 patients in Community or Assisted living, 24 weeks Mean MMSE 12 Psychotropics allowed but stable dosing
Improvement or stabilization of function compared & cognition to placebo
Care givers benefited ~ 1 hr/day
Feldman H. Neurology 2001; 57: 613
![Page 50: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/50.jpg)
Rivastigmine after Donepezil
382 outpatients (MMSE 16) on donepezil changed to rivastigmine in open labeled trial 78 % changed due to lack of efficacy, 3 point
decline in MMSE Improvements seen in cognition, ADLs,
behaviors over baseline
![Page 51: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/51.jpg)
Possible explanations
G1 selectivity BuChE predominance in later disease No up-regulation of AChE with rivastigmine
![Page 52: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/52.jpg)
AChEI & other dementias
Vascular dementia and mixed dementia May have cholinergic deficit Improvement seen in cognition, ADL and
psychiatric inventory compared to placebo 6 month stabilization at baseline
Significant improvements in Lewy Body Dementia
Improvement in dementia associated with Parkinson’s w/o increased symptoms
Erkinjuntti, T. Lancet April 2002; 259:1283-1290Wilkinson, D. Neurology Aug 2003; 61: 479Masterman D.
![Page 53: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/53.jpg)
Namenda & Mixed Dementia
Small studies in mixed vascular dementia similar results as in AD
![Page 54: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/54.jpg)
Memantine for Mild-Moderate ATD
Double-blind, parallel arm, placebo controlled Phase III trial of 24 weeks
403 patients, mean age 77.5 yrs, MMSE 10 to 22
End points: cognition (ADAS-cog), overall function (CIBIC-plus), general function (ADCS-ADL) and behavior (NPI)
Improvement over base line in all areas Only adverse effect -- somnolence
Peskind ER. Poster at AAGP 17th annual meeting
![Page 55: Elephants never get demented I wonder what drugs they’re on? David Greenhouse, MD, CMD Director of Geriatric Education USC SoM.](https://reader035.fdocuments.in/reader035/viewer/2022062517/56649e7e5503460f94b81023/html5/thumbnails/55.jpg)
The Future
Statins & ATD Other vitamins ACheI in severe ATD Secretase inhibitors Amyloid protein antibody Glutamate inhibitors for prevention Anti-amyloid aggregators Tau protein phosphorylation inhibitors