Page 5 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

Research diagnostic criteria for AD generally have been shown to be accurate and reliable based upon
2
pathological confirmation studies; nonetheless, the boundaries between MCI and early AD are not
always clear. Furthermore, among all dementia cases with AD pathology a significant minority will have
concomitant cerebrovascular lesions (infarctions or small-vessel ischemic lesions of the white matter) or
Lewy body pathology akin to Parkinson’s disease (PD). The presence of multiple pathological substrates

associated with AD also can contribute to diagnostic ambiguity. Further developments in structural and
functional neuroimaging techniques, genetic susceptibility testing, and validating biomarker assays will

help clarify diagnostic efforts and inform therapeutic drug testing and monitoring.

AD is estimated to affect 4.5 million individuals in the United States with an average course of about 8 to

3
10 years. Of all individuals over age 65 years, an estimated 6% to 8% have AD or another form of
dementia and this rate exceeds 30% at age 85 years and older. Although different estimates vary, roughly

half of all AD patients are in the early or mild disease stage and the other half are in the moderate to
4
severe range of severity. The projected prevalence of AD will approximately double over the next 20
years, as a result of the aging of the post-WWII baby-boomer generation.

Since the total current economic burden posed by AD, including direct costs (medical, hospital, and
nursing home care) and indirect costs (lost productivity of caregivers) is estimated to exceed $85 billion a

5
year, the current and looming economic impact of AD is staggering. The overall cost of managing AD is
significantly greater for patients with severe disease than for those with mild to moderate; the reasons are
largely greater dependency needs, higher resource utilization, and increased rate of institutionalization.

The comprehensive management of AD entails both nonpharmacologic and pharmacologic interventions.

Nonpharmacologic interventions primarily address behavioral disturbances (e.g., task simplification,
environmental modification, minimal excess stimulation, etc.) and other sources of cognitive impairment
(e.g., treating comorbid medical conditions, minimizing or eliminating drugs with deleterious cognitive
6
side effects). Pharmacologic strategies have focused on modulating disease-associated neurotransmitter
alterations; strategies can be characterized as symptomatic or neuroprotective. Although a symptomatic

and a neuroprotective pharmacologic treatment may have similar outcome characteristics in a clinical
trial, the key difference is that a neuroprotective therapy will have a cumulative benefit that persists after
the treatment is discontinued. Currently available pharmacologic therapies, including cholinesterase

inhibitors (ChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonists, are considered symptomatic
treatments based on their ability to slow the clinical progression of symptoms across cognitive,
behavioral, and functional domains.

Alzheimer's Drugs Page 5 of 205