Dementia treatment versus prevention

Abstract

Alzheimer disease (AD) and dementia are becoming increasingly prevalent due to the aging of the global populations. Currently available treatment options, including acetylcholinesterase inhibitors and memantine, only have symptomatic effects and no drugs with disease-modifying properties are available. Research on the amyloid cascade indicates that amyloid-β (Aβ) clearance from the brain may be the main pathophysiological change in late-onset AD and the key driver of neurodegeneration, which ultimately results in progressive cognitive deterioration and dementia. Most new AD drug candidates target different aspects of Aβ clearance, eg, using passive anti-Aβ immunization, but so far, all efforts to develop more effective drugs have failed. In parallel, nonpharmacological prevention trials are being conducted to modify dementia risk associated with known epidemiological risk factors. Some initial results are promising, but replication across independent cohorts remains a challenge.

Keywords: Alzheimer disease; biomarker; clinical trial; dementia; epidemiology; mild cognitive impairment; prevention; prognosis; public health; treatment.

Figure 1.. Schematic representation of key amyloid-β clearance pathways (modified from ref 70: Tarasoff-Conway JM, Carare RO, Osorio RS, et al. Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol. 2015;11(8):457-470. © Springer Nature Publishing, 2015). Aβ, amyloid-β; CSF, cerebrospinal fluid; ISF: interstitial fluid; BBB, blood-brain barrier