Reimagining Alzheimer´s disease:

Some thoughts

Mary Sano, PhD

Alzheimer Disease Research Center
Mount Sinai School of Medicine, NYC, NY
 Age Based Hypothesis
• A hypothesis MUST be testable
• An “injury” MUST be measurable
• Age is certainly a risk for AD but the assumption
that AD is “different” than aging must be
reconciled with high rates of AD pathology in
clinically normal elders.
 The Challenge
• Sporadic AD has a clinical prodrome
• Memory and other cognitive deficits precede the
frank expression of disease
AND
• Not all with these deficits have AD
• Models of disease “initiation” via inflammatory
mechansims must reconcile with clinical findings
 Anti-inflammatories have no benefit on
dementia or cognition
• Use of naproxen or celecoxib did not improve
cognitive function. There was weak evidence for a
detrimental effect of naproxen.
• In persons without dementia there is an attenuation
of the detrimental effect, BUT no benefit or
evidence of protection from cognitive decline.
(Adapt Research Group Arch Neurol, 2008)