認知症の診断と治療　―Alzheimer病を中心に―

抄録

According to estimates by the Ministry of Health, Labor and Welfare, the number of dementia patients in 2012 was 4.62 million, and the number of mild cognitive impairment patients was about 4 million. The typical symptoms of Alzheimer disease (AD) include time disorientation and delayed recall disturbance. Cerebral blood flow single photon emission computed tomography (CBF–SPECT) shows poor blood flow in the posterior cingulate gyrus and/or precuneus in AD patients. In vascular dementia, cognitive impairment is milder than in AD, and there are clinical courses such as stepwise exacerbation of symptoms, and various cerebrovascular lesions are observed on brain MRI. The patients with dementia with Lewy bodies have clinical symptoms such as visual hallucinations and Parkinsonian symptoms. CBF–SPECT and MIBG myocardial scintigraphy show the decreases of occipital lobe blood flow and cardiac uptake, respectively.

At the present, acetylcholinesterase inhibitors and the NMDA receptor antagonist memantine are currently available for the treatment of AD. Although these drugs are limited to symptomatic therapy in AD patients, recently, approaches aimed at disease–modifying therapy (DMT), especially the approaches focused on amyloid β–protein (Aβ) have been developed remarkably. Clinical trials of anti–Aβ antibodies have repeatedly reported poor results, but clinical trials of anti–Aβ antibodies that target Aβ aggregates, such as aducanumab and lecanemab, have reported significant effects on the primary endpoint in phase 3 trials. In 2021, aducanumab was approved in the United States, albeit with conditions. The approval of aducanumab in Japan was subject to continued deliberation. In 2023, lecanemab was approved in the United States, and finally in Japan. Although some issues such as amyloid–related imaging abnormalities (ARIA) should be resolved, the treatment of AD is about to take a new turn at now.