認知症の概念と疾患修飾薬開発

抄録

Alzheimer's disease (AD) is a neurodegenerative process that progresses from normal to mild cognitive impairment and from mild cognitive impairment to dementia referred to as AD continuum. Cholinesterase inhibitors and NMDA receptor antagonist can only be used in dementia stage but not in mild cognitive impairment stage. Research communities have presented a hypothesis that amyloid and tau are two major players that contribute to cause neuron death and dementia alone or in combination. In Tohoku University, we have a long experience of developing new biomarkers that help making clinical trials successful. However, it is a great disappointment that all of the clinical trials of disease–modifying drugs (DMDs) were unsuccessful or halted due to lack of clinical benefits or due to incident adverse effects in treated group compared to placebo group. In the most recent clinical trials of amyloid–directed DMDs, only participants with amyloid positivity demonstrated by baseline amyloid PET or decreased cerebrospinal fluid amyloid–β₄₂ were recruited in order to exclude non–AD participants. Such clinical trials with DMDs are currently in progress predominantly in prodromal and preclinical AD, but not in AD dementia. Research communities hope that we are able to stop AD by effective preemptive therapies before symptoms begin. We hope that AD can be preventable disease by 2025.