Diagnosis and treatment of dementia focusing on Alzheimer's dementia

Abstract

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. For the diagnosis of dementia, treatable dementia is first ruled out, and then common dementia such as Alzheimer disease (AD), vascular dementia (VaD), and dementia with Lewy bodies (DLB) are differentiated. The typical symptoms of 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 VaD, 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 DLB 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. Anti–Aβ antibody therapy is central to the current development of DMT for AD. 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.