Treatment AD MSK March112018
Treatment AD MSK March112018
Treatment AD MSK March112018
Pondicherry
March 11 2018
Burden of Dementia
• 47 million people globally are living with dementia today.
http://www.alz.co.uk/research/world-report-2011
Alzheimer’s Disease:
More Than Just Memory Loss
Death
Functional
Cognition Independence
Deterioration
Motor
Mood
Behavior
• Family History
FDG-PET
Hypometabolism
in medial parietal and lateral
temporal-parietal isocortex
MRI
Atrophy in the medial temporal
allocortex and basal-lateral temporal isocortex
Amyloid PET
Ligand
Uptake in Jack et al,
isocortex Neurology® 2016;87:539–547
Longitudinal Changes of
Alzheimer Disease Biomarkers
• Current treatments
– Acetylcholinesterase inhibitors
• Donepezil
• Rivastigmine
• Galantamine
– NMDA antagonist
• Mementine
Treatment of AD
• Experimental treatments
– Disease modifying approaches
• Modulation of amyloid deposition
• Modulation of tau deposition
• Additional approaches (eg., cholesterol and vascular related
risk factors)
– Preventive approaches
• Antioxidant therapy
• Anti inflammatory therapy
Timeline of the emergence of various
experimental and clinical therapies for AD
www.progressnp.com
Donapezil 23 mg/d
• Compared with patients who continued taking donepezil 10 mg/d,
those whose dose was increased to donepezil 23 mg/d demonstrated
a significantly greater cognitive benefit on the Severe Impairment
Battery after 6 months of treatment
• Other therapies (exercise therapy, animal-assisted therapy, special care unit and dining room
environment-based interventions)
1.The patient and (or) their proxy decision maker decide to stop
7. Progression to a stage of the disease where there is no significant benefit from continued
therapy
Hogan DB et al, Alzheimers Dement. 2007;3:355–384
Amyloid cascade hypothesis of AD
• Additional approaches
– Oxidative damage
– Inflammation
– Iron dysregulation
– Cholesterol metabolism
Konstantina G, Ther Adv Neurol Disord (2013) 6(1) 19–33
Sites of action of
future drug treatments
www.progressnp.com
Subgroups of AD
Iqbal K & Iqbal IG. Alzheimers Dement. 2010 September ; 6(5): 420–424
Amyloid-β immunotherapy
• Preclinical studies support the idea that AD can be prevented by amyloid-β (Aβ)
immunotherapies
• Adverse events, but some efficacy, were observed in clinical trials of the AN1792 Aβ vaccine
and the passive Aβ immunotherapy bapineuzumab
• Second-generation Aβ vaccines that avoid the adverse events observed with AN1792 and
improve antibody generation might improve Aβ immunotherapy efficacy
Lemere CA & Masliah E. Nat Rev Neurol. 2010 February ; 6(2): 108–119
Active immunotherapy for AD
• Development of an immunotherapy that can delay AD onset by 5
years would reduce the prevalence of the disease by half
• LH ablating therapies
Preventive therapies
• Antioxidant therapy
– Oxidative stress
– Reactive oxygen species (ROS)
– MitoQ
– ALCAR and LA
• Anti-inflammatory therapy
– NSAID and low risk for AD
– Naproxen
• It has also been shown that treatment with antioxidants vitamin E, vitamin C,
selegiline, estrogen, Ginkgo biloba, and so forth may exert certain positive effects
on the development of AD
• But the efficacy of those antioxidants in clinical patients is still controversial and not
so conclusive
• Clinical trials for AD prevention and treatment by antioxidants are still in their
infancy
Feng Y & Wang X. Oxidative Medicine and Cellular Longevity Volume 2012 Article ID 472932
Nutrition
• Mediterranean diet (plant-based foods in abundance, fresh fruit as
the typical daily dessert, olive oil as the principal source of fat, dairy
products - principally cheese and yogurt, fish and poultry consumed
in low to moderate amounts, zero to four eggs consumed weekly, red
meat consumed in low amounts and wine consumed in low to
moderate amounts)
Thaipisuttikul P & Galvin JE, Clin Pract (Lond). 2012 March ; 9(2): 199–209
Nonpharmacological Treatment of AD
• TMS/tDCS may have therapeutic utility in AD, but evidence is still very
preliminary
• TMS/tDCS appear safe in AD, but longer-term risks have been insufficiently
considered
Freitas C et al, Exp Gerontol. 2011 August ; 46(8): 611–627
Deep brain stimulation for AD
• The evidence of functional alterations in memory networks is commonly seen in AD
patients