The document discusses current issues in diagnosing and treating Alzheimer's disease. It outlines the three stages of Alzheimer's (preclinical, mild cognitive impairment, dementia) and biomarkers used for diagnosis. It also discusses FDA-approved drugs for treatment including donepezil, rivastigmine, galantamine, and memantine. Clinical trials show these drugs can improve cognition and function compared to placebo. Non-drug approaches like lifestyle changes and supplements are also mentioned.
Brand name : NAMENDA
US FDA Approval :October 2003
NMDA (N-methyl-D-aspartate) receptor antagonist
Indicated for the treatment of moderate to severe Alzheimer’s Disease
Brand name : NAMENDA
US FDA Approval :October 2003
NMDA (N-methyl-D-aspartate) receptor antagonist
Indicated for the treatment of moderate to severe Alzheimer’s Disease
Escitalopram 10 mg film coated tablets smpc- taj pharmaceuticalsTaj Pharma
Escitalopram Taj Pharma : Uses, Side Effects, Interactions, Pictures, Warnings, Escitalopram Dosage & Rx Info | Escitalopram Uses, Side Effects -: Indications, Side Effects, Warnings, Escitalopram - Drug Information - Taj Pharma, Escitalopram dose Taj pharmaceuticals Escitalopram interactions, Taj Pharmaceutical Escitalopram contraindications, Escitalopram price, Escitalopram Taj Pharma Escitalopram 10 mg Film-coated Tablets SMPC- Taj Pharma . Stay connected to all updated on Escitalopram Taj Pharmaceuticals Taj pharmaceuticals Hyderabad.
Management of High Disease Activity in Multiple Sclerosis (MS)Sudhir Kumar
Multiple sclerosis is a common disease affecting the central nervous system. Immunotherapy with interferon is the first line therapy for MS. This presentation discusses the treatment options of high disease activity in patients with MS. Role of natalizumab (tysabri) has been highlighted.
Multiple sclerosis is a demyelinating disease affecting brain, optic nerves and spinal cord. It is characterised by frequent relapses. Now, there are a number of effective treatment options for MS. Earlier, only clinical parameters were considered to evaluate the efficacy of MS treatments. However, now, we need to look at disability as well as MRI parameters. All these points are included in NEDA (no evidence of disease activity). This presentation looks at the definition and classification of NEDA. It also looks at NEDA rates with various treatment options.
A description of Brivaracetam, a novel SV2A ligand, an anti-epileptic with greater potency and significantly reduced behavioural adverse effects compared to Levetiracetam .
Gabantin (Gabapentin Capsules) is used for the management of postherpetic neuralgia in adults. It is also used for the adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy
Chair & Presenter, Bruce Cree, MD, PhD, MAS and Lauren B. Krupp, MD, prepared useful Practice Aids pertaining to multiple sclerosis for this CME/MOC/NCPD/CPE activity titled “Exploring the Convergence of Advances in S1P Receptor Modulation With Progress in Understanding Brain Atrophy and Cognition Measures in Multiple Sclerosis.” For the full presentation and complete CME/MOC/NCPD/CPE information, and to apply for credit, please visit us at http://bit.ly/2ZRy5Ys. CME/MOC/NCPD/CPE credit will be available until November 25, 2022.
Zonisamide is among the newer broad spectrum anti-epileptic drugs, effective against focal and generalized epilepsies. It can be taken once daily and is well tolerated. The current article focuses on clinical efficacy and safety of zonisamide in epilepsy (as add on or as monotherapy). There is long term data as well as comparative studies against carbamazepine.
Escitalopram 10 mg film coated tablets smpc- taj pharmaceuticalsTaj Pharma
Escitalopram Taj Pharma : Uses, Side Effects, Interactions, Pictures, Warnings, Escitalopram Dosage & Rx Info | Escitalopram Uses, Side Effects -: Indications, Side Effects, Warnings, Escitalopram - Drug Information - Taj Pharma, Escitalopram dose Taj pharmaceuticals Escitalopram interactions, Taj Pharmaceutical Escitalopram contraindications, Escitalopram price, Escitalopram Taj Pharma Escitalopram 10 mg Film-coated Tablets SMPC- Taj Pharma . Stay connected to all updated on Escitalopram Taj Pharmaceuticals Taj pharmaceuticals Hyderabad.
Management of High Disease Activity in Multiple Sclerosis (MS)Sudhir Kumar
Multiple sclerosis is a common disease affecting the central nervous system. Immunotherapy with interferon is the first line therapy for MS. This presentation discusses the treatment options of high disease activity in patients with MS. Role of natalizumab (tysabri) has been highlighted.
Multiple sclerosis is a demyelinating disease affecting brain, optic nerves and spinal cord. It is characterised by frequent relapses. Now, there are a number of effective treatment options for MS. Earlier, only clinical parameters were considered to evaluate the efficacy of MS treatments. However, now, we need to look at disability as well as MRI parameters. All these points are included in NEDA (no evidence of disease activity). This presentation looks at the definition and classification of NEDA. It also looks at NEDA rates with various treatment options.
A description of Brivaracetam, a novel SV2A ligand, an anti-epileptic with greater potency and significantly reduced behavioural adverse effects compared to Levetiracetam .
Gabantin (Gabapentin Capsules) is used for the management of postherpetic neuralgia in adults. It is also used for the adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy
Chair & Presenter, Bruce Cree, MD, PhD, MAS and Lauren B. Krupp, MD, prepared useful Practice Aids pertaining to multiple sclerosis for this CME/MOC/NCPD/CPE activity titled “Exploring the Convergence of Advances in S1P Receptor Modulation With Progress in Understanding Brain Atrophy and Cognition Measures in Multiple Sclerosis.” For the full presentation and complete CME/MOC/NCPD/CPE information, and to apply for credit, please visit us at http://bit.ly/2ZRy5Ys. CME/MOC/NCPD/CPE credit will be available until November 25, 2022.
Zonisamide is among the newer broad spectrum anti-epileptic drugs, effective against focal and generalized epilepsies. It can be taken once daily and is well tolerated. The current article focuses on clinical efficacy and safety of zonisamide in epilepsy (as add on or as monotherapy). There is long term data as well as comparative studies against carbamazepine.
Nueva diana hipolipemiante: terapia anti-PCSK9
02/06/2016 18:30h Casa del Corazón, Madrid
http://antipcsk9.secardiologia.es
#antiPCSK9
Resultados de la inhibición de PCSK9: superando los límites
Dr. José Luis Zamorano Gómez, Hospital Universitario Ramón y Cajal (Madrid)
@cardioXXI
New Treatment Devices and Clinical Trials jgreenberger
Dr. Kathryn Davis from Penn Epilepsy Center present on new treatment devices and clinical trials for epilepsy. From the 2014 Epilepsy Education Exchange.
ARNI as new standard of care in Heart Failure SYEDRAZA56411
Angiotensin Receptor Blocker -Neprilysin Inhibitor combination has an important role to play in patients with Heart Failure with reduced ejection fraction. ARNI is now first line medication in HRrEF
Journal Club about the Phase 2 study of Selonsertib in Diabetic Kidney Disease to Our Division on 12/9/19.
Also an intro about the Phase 3 study (MOSAIC) we will be launching before the end of the year
My presentation delivered at the MS Symposium of the Jewish Hospital Berlin (https://www.juedisches-krankenhaus.de/home.html) held on 29 Nar 2023 at the Centrum Judaicum, Oranienburger Strasse, Berlin
Similar to Current Issues in the Diagnosis and Treatment of Alzheimer's (20)
Donna Weihofen, retired Senior Nutritionist spoke about Eating the Mediterranean Way at Wisconsin Women's Health Foundation's 2013 annual Gathering in Marshfield, WI. The Mediterranean diet emphasizes:
• Eating primarily plant-based foods, such as fruits and vegetables, whole grains, legumes and nuts
• Replacing butter with healthy fats, such as olive oil
• Using herbs and spices instead of salt to flavor foods
• Limiting red meat to no more than a few times a month
• Eating fish and poultry at least twice a week
• Drinking red wine in moderation (optional)
Cathy Taylor, LPN, BA, presented on laughter and stress management in her presentation Stress in the 21st Century, at the Wisconsin Women's Health Foundation's 2013 annual Gathering event in Marshfield, WI.
Kristie Rauter, Community Health Improvement Planner from the Wood County Health Department, presented on Get Active Wood County, an initiative aimed at obesity prevention at the Wisconsin Women's Health Foundation's Annual Gathering event. She spoke about the collaboration between the Health Department, local businesses, schools and non-profit organizations to create a healthier Wood County.
2012 Dialogue presentation by Chanel Tyler, MD – Assistant Professor, Department of Obstetrics and Gynecology at the UW School of Medicine and Public Health
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Current Issues in the Diagnosis and Treatment of Alzheimer's
1. Current Issues In The Diagnosis
and Treatment of Alzheimer’s
Malgorzata Franczak, MD
Associate Professor of Neurology
Medical College of Wisconsin
Director of the Normal Pressure Hydrocephalus Program
Director of the Community Engagement
3. In 2011 The National Institute on Aging and
The Alzheimer’s Association proposed new
criteria and guidelines for diagnosing
Alzheimer’s Disease
15
4. Three stages of Alzheimer’s Disease
A. Preclinical AD
B. Mild Cognitive Impairment due to AD
C. Dementia due to AD
Biomarkers tests
A. Biomarkers showing levels of beta-amyloid accumulation
in the brain
B. Biomarkers showing that neurons in the brain are injured
or actually destroyed
15
5. Preclinical Alzheimer’s Disease
1. Individuals have no symptoms
2. Measurable changes in the brain, CSF and/or blood that
indicate the earliest signs of disease are found
15
7. Mild Cognitive Impairment (MCI)
1. Memory complaint, preferably corroborated by
an informant
2. Memory impairment documented according to
appropriate reference values
3. Essentially normal performance in non memory
cognitive domains
4. Generally preserved activities of daily living
5. Not demented
15
9. Hypothetical temporal ordering of neuropathological
processes in the course of Alzheimer disease and
corresponding imaging and biomarker measures
Petersen, R. C. et al. Arch Neurol 2009;66:1447-1455.
Copyright restrictions may apply.
11. Treatment Goals
Maintain quality of life
Maximize function
Enhance cognition
Treat mood and behavior problems
Educate and counsel caregiver to alleviate stress
Regular office visits
Frequent telephone contact with family members
Coordination of multidisciplinary team
12.
13. FDA-approved
drugs commonly used for the treatment of AD
Aricept® (donepezil hydrochloride)
Indicated for mild, moderate, or severe dementia of the Alzheimer’s type
Exelon® (rivastigmine tartrate) and EXELON®PATCH (rivastigmine
transdermal system)
Indicated for mild to moderate dementia of the Alzheimer’s type
Indicated for mild to moderate Parkinson’s disease dementia (PDD)
Razadyne® (galantamine hydrobromide)
Indicated for mild moderate and advanced dementia of the Alzheimer’s type
Namenda® (memantine hydrochloride) is an NMDA receptor
antagonist
Indicated for moderate to severe dementia of the Alzheimer’s type
Aricept® is a registered trademark of Eisai Incorporated; Razadyne ® is a registered trademark of Ortho-McNeil Neurologics
Incorporated; Namenda® is a registered trademark of Forest Pharmaceuticals Incorporated.
14. P<.001
MMSE change from baseline
1.0
Clinical
improvement
P=.019
0.5
P=.001
P<.001
0.0
-0.5
-1.0
-1.5
-2.0
Aricept (n=142)
Placebo (n=144)
-2.5
-3.0
0
12
24
36
52 Endpoint
Study week
Adapted with permission from Winblad et al. Neurology. 2001;57:489-495.
See Appendix for study description and safety information (Nordic).
Clinical
decline
15. MMSE change from baseline
Clinical
improvement
3
P=.0004
P<.0001
P=.0019
2
1
0
-1
Aricept (n=144)
Placebo (n=146)
Clinical
decline
-2
0
12
24
Endpoint
Study week
Adapted with permission from Feldman et al. Neurology. 2001;57:613-620.
See Appendix for study description and safety information (Moderate to Severe AD [MSAD]).
16. Tpmx82250816Alzheimer’s.v2 - 19
6/27/02 13:47
Mean Change From Baseline
± SE in ADAS-cog/11
GAL-USA-9: Change From
Baseline in ADAS-cog/11 Scores
-6
-4
-2
0
2
4
6
8
10
12
14
16
18
20
22
24
Baseline 3
12-month Placebo 1
Estimation of decline–Stern Equa tion2
Galantamine 24-32/24 mg 3
6
9
12
18
Time (months)
24
30
36
1. Torfs K et al Poster presented at the Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer
Therapy, April 2000. 2. Ster n RG et al. Am J Psychiatry. 1994;151:3. 3. Data on file. Janssen Pharmaceutica.
17. Donepezil-treated group
95% confidence interval
Historical control
Mean change (± SE) from
baseline in ADAS-cog scores
-10
0
10
20
30
40
50
60
14
26 38 50 62 74 86 98 110 124 136 146 158 170 182 194 206 213 230 242 254
Weeks
Reprinted with permission from Rogers SL et al. Eur Neuropsychopharmacol. 2000;10:195-203.
18. Aricept 10 mg
357 days
(n=214 at baseline)
P<.002
Placebo
208 days
(n=217 at baseline)
0
50
100
150
200
250
Median time to functional decline (days)
Mohs et al. Neurology. 2001;57:481-488.
See Appendix for study description and safety information (Preservation of Function).
300
350
19. Aricept 23 mg
Screened 2186
Randomized 1467
Donepezil 23 mg
963
Donepezil 10 mg
471
Completed
399
Withdrawn
72
Reason for withdrawal
AE 8.1%
Lack of efficiency 0.1
Other 7
Completed
687
Withdrawn
278
Reason for withdrawal
AE 18.6%
Lack of efficiency 0
Other 9.1
22. EXELON Patch is applied once daily
Maintenance Rx
Initial Rx
4 WEEKS**
EXELON Patch
4.6 mg/24h
Daily Rivastigmine
Oral Dosage
EXELON Patch
9.5 mg/24h
Daily EXELON
Patch Dosage
<6 mg
4.6 mg/24 h
6 to 12 mg
9.5 mg/24 h
*Dose should be increased after a minimum of 4 weeks only if initial dose is well
tolerated. When switching from oral rivastigmine, apply the first patch on the day
following the last oral dose.
Exelon Patch prescribing information. Novartis Pharmaceuticals Corporation, East Hanover, NJ, 2007.
27. Memantine in Moderate to Severe AD Study
The Memantine Group Exhibited Significantly Superior Cognitive
Function Compared With the Placebo Group
P<.001
0
-2
*P=.002
-4
†
P<.001
Deterioration
Mean Change From Baseline
in SIB Score
Improvement
P=.068
2
-6
-8
Memantine
-10
Placebo
-12
0
n=
n=
*.
4
12
126
126
119
117
107
106
Week
28
End Point
96
83
124
123
33. Figure 2. Dynamic biomarkers of the Alzheimer's pathological cascade
Aβ is identified by CSF Aβ42 or PET amyloid imaging. Tau-mediated neuronal injury
and dysfunction is identified by CSF tau or fluorodeoxyglucose-PET. Brain structure
is measured by use of structural MRI. Aβ=β-amyloid. MCI=mild cognitive impairment.
34.
Prevent build up of plaque (anti-amyloid)
o
o
slow aggregation into plaques
o
dissolve plaques
o
slow or prevent amyloid production by inhibiting clipping enzymes
or by vaccine therapy
increase clearance
Prevent build up of paired helical
filaments (tau focused)
o
o
slow or prevent tau aggregation and dysfunction
dissolve paired helical filaments
Prevent brain cell dysfunction and death
o
slow or prevent oxidative stress, inflammation, reduced blood flow
o
increase levels of protective molecules in brain
o
maintain viable connections between cells
Editor's Notes
Purpose:
The treatment goals are to maintain quality of life and maximize function and cognition in these
individuals.
Key Points:
Evaluation and treatment of mood and behavior disorders play an important role in the treatment of patients with AD.
Similarly, we don’t want to forget the importance of the caregiver. Look for stress and/or depression among caregivers.
It’s important not just to make a diagnosis and reevaluate in 6 or 12 months, but to provide periodic surveillance if medication or therapy is employed for the disease.
Telephone contact is helpful for many AD patients and their families.
Speaker Highlights
Key point:
Currently, there are four commonly used pharmacologic agents approved for the treatment of dementia of the Alzheimer’s type: Aricept® (donepezil HCl), EXELON® (rivastigmine tartrate) and EXELON®PATCH (rivastigmine transdermal system), Razadyne® (galantamine HBr), and Namenda® (memantine HCl).
Supplemental notes:
The cholinesterase inhibitors Aricept, EXELON, and Razadyne are thought to exert their therapeutic effect by enhancing cholinergic function by inhibition of cholinesterase enzymes.1-3
Namenda is thought to exert its therapeutic effect by inhibiting the effects of the excitatory amino acid glutamate at N-methyl-D-aspartate (NMDA) receptors in the CNS.4
References
Aricept Tablets and Orally Disintegrating Tablets prescribing information. Eisai Incorporated, Teaneck, NJ, 2006.
Exelon Capsules and Oral Solution prescribing information. Novartis Pharmaceuticals Corporation, East Hanover, NJ, 2007.
Exelon Patch prescribing information. Novartis Pharmaceuticals Corporation, East Hanover, NJ, 2007.
Razadyne Tablets, Oral Solution, and Extended-Release Capsules prescribing information. Ortho-McNeil Neurologics Incorporated, Titusville, NJ, 2006.
Namenda Tablets and Oral Solution prescribing information. Forest Pharmaceuticals Incorporated, St. Louis, MO, 2007.
Key Points
In the first 1-year, multinational, double-blind study of a cholinesterase inhibitor (ChEI) in AD, Aricept was effective as persistent treatment.19
Cognition, as measured by the MMSE, remained at or near baseline beyond 6 months (mean baseline MMSE, 19.3).
Significant differences for Aricept compared with placebo were demonstrated at Weeks 24, 36, and 52 (P<.02).
See Appendix for study description and safety information (Nordic).
Key Points
This was the first double-blind study of a ChEI in more advanced AD.20
In this study, Aricept improved cognition, with standardized MMSE scores remaining above baseline for 6 months (mean baseline MMSE, 11.7).
Significant differences for Aricept compared with placebo were demonstrated at Weeks 12 and 24 (P.0019).
The MMSE is less sensitive to changes in cognition as the disease progresses to more advanced stages (exhibits a floor effect).
See Appendix for study description and safety information (Moderate to Severe AD [MSAD]).
Key Points
Behavior was evaluated in the 24-week, multicenter, randomized, double-blind, placebo-controlled MSAD study.20
NPI scores of Aricept-treated patients were improved from baseline throughout the study and significantly different from placebo at Weeks 4 and 24.
NPI scores of placebo-treated patients were relatively unchanged, remaining near baseline.
See Appendix for study description and safety information (MSAD).
Key Points
The effects of Aricept treatment on functional decline in patients with mild to moderate AD were determined in a 1-year, double-blind, placebo-controlled study.15
Time to reach clinically evident functional decline was measured using the ADFACS.
Patients exited the study when they experienced a 20% decline in instrumental ADLs, a decline in the ability to perform 1 or more basic ADLs, or a 1-point increase in the Clinical Dementia Rating (CDR) scale.
Aricept significantly extended the median time to clinically evident functional decline by 5 months versus placebo in this 1-year study. Aricept-treated patients maintained function 72% longer than placebo-treated patients (median of 357 vs 208 days) (P<.002).
See Appendix for study description and safety information (Preservation of Function).
Speaker Highlights
Key points:
Treatment is started with EXELON Patch 4.6 mg/24h. After a minimum of 4 weeks of treatment, and if well tolerated, the dosage should be increased to 9.5 mg/24h, which is the recommended effective dosage.
Patients treated with EXELON capsules or oral solution can be switched to EXELON Patch as follows:
If on a total daily oral dose of <6 mg, can switch to EXELON Patch 4.6 mg/24h
If on a total daily oral dose of 6–12 mg, can switch to EXELON Patch 9.5 mg/24h
Supplemental note:
The first Patch should be applied on the day following the last oral dose.
Reference
Exelon Patch prescribing information. Novartis Pharmaceuticals Corporation, East Hanover, NJ,
2007.
Speaker Highlights
Key point:
The observed rates of nausea and vomiting associated with EXELON Patch 9.5 mg/24h treatment approached those observed in the placebo group and are reduced compared with EXELON capsule.
Supplemental note:
Gastrointestinal adverse effects, including nausea and vomiting, can be significant and at times severe at higher-than-recommended doses. The dose should be titrated as prescribed and reinitiated at the lowest dose if interrupted for more than a few days.
Reference
Exelon Patch prescribing information. Novartis Pharmaceuticals Corporation,
East Hanover, NJ, 2007.
Purpose:
To highlight the difference between the mechanism of action (MOA) of memantine and
the MOA associated with the ChEIs as a class.
Key Points:
Memantine1
Memantine may block sustained activation of NMDA receptors by abnormal glutamate activity.
It is thought that by blocking NMDA receptor calcium channels, memantine inhibits the sustained, low-level influx of excitatory calcium (Ca2+) ions into postsynaptic glutamatergic neurons, thereby preventing the harmful consequences that have been attributed to the persistent activation of such neurons.
Memantine may restore normal glutamate function, which is important for learning and memory.
ChEIs2,3
It is believed that the symptoms of AD are caused, in part, by pathologic deficits in cholinergic neurotransmission. These deficits have been ascribed to the progressive loss of acetylcholine-producing neurons in patients with AD.
Purpose:
To summarize cognitive outcomes in the Reisberg trial.
Key Points:
Orientation to slide:
—Points on the y-axis represent mean change in Severe Impairment Battery (SIB) score from baseline while points on the x-axis represent time.
— As higher scores indicate better performance than placebo on cognitive tasks, positive mean
changes above baseline indicate clinical improvement.
There was a significant difference on the SIB outcome measure favoring memantine treatment at end point
Over the 6-month period, memantine patients decreased by 3.9 points at end point, while placebo patients decreased by 9.8 points. Therefore, memantine patients had significantly less cognitive decline on the SIB total score compared with placebo.
Additional Information:
The SIB evaluates cognitive performance in moderate to severe AD. It includes a 40-item scale, which measures such skills as attention, language, praxis, visuospatial ability, construction, memory, and social interaction. The test is scored from 0 (greatest impairment) to 100.
SIB baseline scores were 68.3 for placebo and 65.9 for memantine.
Alzheimer’s Disease Cooperative Study (ADCS) reports that for patients with untreated AD whose MMSE scores are 5-9, the average deterioration rate on the SIB is roughly 3.19 points per month; and for patients with untreated AD whose MMSE scores are 10-15, the rate of change is 2.08 points per month. Over the
6-month period, this resulted in a 12- to 18-point drop.
Purpose:
To summarize functional outcomes.
Key Points:
Orientation to slide:
Points on the y-axis represent mean changes in Alzheimer’s Disease Cooperative Study–
Activities of Daily Living (19 item) (ADCS-ADL19) scores from baseline while points
on the x-axis show when measurements were taken.
As with the SIB scale, higher scores indicate better functioning than placebo; hence, positive changes above baseline represent an improvement in functional ability.
Patients in the memantine group demonstrated significantly less deterioration in functional performance as measured by ADCS-ADL19 than patients in the placebo group over the course of the study.
At end point, memantine patients declined by approximately 3 points while placebo patients declined by approximately 5 points.
Additional Information:
The ADCS-ADL19 inventory is a comprehensive battery of ADL/instrumental ADCS questions aimed at measuring the functional ability of patients with moderate to severe AD. It includes a subset of 19 items selected to best assess moderate to severe patients. The ADCS-ADL19 determines a patient’s ability to perform ADL ranging from total independence to total disability. Some of the 19 items evaluated included eating, walking, toileting, bathing, grooming and dressing, attending to conversation, doing household activities, and traveling beyond home.