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Such trials need to recruit large numbers of participants with either no cognitive impairment or with minimal problems such as isolated memory complaints. The studies must continue for a number of years rather than a number of months as would be typical for the case of a new symptomatic treatment. As a result, the safety and tolerability of any intervention becomes critical and at least one study, the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) with the non-steroidal anti-inflammatory drugs (NSAIDs) naproxen and celecoxib, has been terminated because of safety concerns [16].

Direct medical costs account for the remaining 16% [5]. I. 2 National Models 23 In the real world, statistics take on flesh and blood significance as a victim’s memory, reason, judgment, and language are inevitably destroyed. Tens of millions of children and grandchildren, wives, husbands, sons, and daughters of AD patients struggle daily with the overwhelming physical and emotional burden of caring for loved ones who may not even recognize or acknowledge them. Here again, the developing world represents the tip of the epidemiological iceberg: In 2010, LDCs accounted for 14% of AD cases, but less than 1% of total worldwide expenditures.

Biomarkers of these processes are increased CSF tau and structural magnetic resonance imaging measures of cerebral atrophy. Neurodegeneration is accompanied by synaptic dysfunction, which is indicated by decreased fluorodeoxyglucose uptake on PET [11]. The hypothetical model attempts to relate the disease stage to AD biomarkers in which Aß biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and that the neurodegenerative biomarkers correlate with clinical symptom severity [11].

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