Dementia with Lewy bodies and Parkinson disease dementia, their diagnoses and treatment strategies

Abstract

Dementia with Lewy bodies (DLB) is a form of dementia characterized by hallucinations and delusions. The concept of DLB was first reported in the world by Kosaka et al. as a disease in which Lewy bodies, which are unique neural inclusions, are found in autopsy brains, and the disease concept has been established. On the other hand, Parkinson's disease (PD), which shows characteristic motor symptoms such as tremor, muscle rigidity, and akinesia, shows Lewy body pathology due to damage to dopamine neurons in the substantia nigra, and as the disease progresses, Lewy bodies spread throughout the brain and eventually cause dementia. The clinical features of PD dementia (PDD) is quite similar to those of DLB and furthermore, the pathology of PDD is indistinguishable from that of DLB. For these reasons, it is now considered appropriate to refer to both disorders collectively as Lewy body disease. Although pharmacotherapy, mainly dopamine replacement, has shown remarkable efficacy in improving motor dysfunction in PD, it is not effective enough to treat a wide variety of non-motor symptoms, including cognitive dysfunction. It is now clear that the most important determinant of prognosis in PD is the degree of concomitant cognitive dysfunction. Recent studies have shown that the prognosis for PD is generally 3-4 years from the onset of dementia, regardless of disease duration or age of onset. It is also clear that more than 80% of PD patients will eventually develop dementia. Therefore, it is essential to establish a methodology for early detection and intervention of PD dementia. We performed the OSIT-J olfaction test in PD patients without dementia and examined its association with future onset of dementia. Results showed that about half of the patients with severe olfactory impairment (OSIT-J ≤ 4) had slightly lower cognitive function scores from the time of entry. In addition, longitudinal results showed that 10 of the 44 PD patients in the study developed new dementia during the 3-year outpatient period, all of whom had severe olfactory impairment at study entry. It was also found that brain atrophy and cerebral metabolic abnormalities were prominent in patients with severe hyposmia, even when motor impairment was mild (Brain 135:161-169, 2012). This study is the first to show that severe hyposmia is predictive of dementia in PD. Similar results have been replicated around the world. Based on these results, a randomized, double-blind, comparative study of donepezil as a biomarker for olfactory impairment in PD (DASH-PD study) was initiated as a multicenter study at 22 centers nationwide to establish an early diagnosis and treatment intervention for dementia in PD, and a 4-year follow-up period was completed. The results suggest the efficacy and safety of cholinesterase inhibitors for PD without dementia and were recently reported (eClinicalMedicine 51: 101571, 2022).