LBD is now defined as follows: “LBD is a chronic progressive neuropsychiatric disorder, which is clinically characterized by Parkinson symptoms of presenile or senile, or often younger onset, usually followed by dementia at the later stages. Case by case, progressive dementia or various kinds of psychiatric symptoms including characteristic visual hallucination and delusions are the chief symptoms, frequently followed by Parkinson symptoms. It is neuropathologically characterized by numerous Lewy bodies and Lewy neurites (Lewy pathology), and neuronal cell loss in the central and autonomic nervous systems.” Yoshimura [16] reconfirmed our study of LBD when he was in Vienna and proposed the term DLBD in 1983. Based on our 11 autopsied cases with the diffuse type of LBD, we [13, 17] also proposed the term “diffuse Lewy body disease (DLBD)” in 1984 and 1990.

DLBD was defined as follows: DLBD is characterized clinically by progressive dementia and Parkinson symptoms of presenile or senile, or sometimes younger onset, and neuropathologically by numerous Lewy bodies and neuronal cell loss in the central and autonomic nervous systems, frequently followed by various degrees of Alzheimer pathology.”

Since we intensified in our paper of 1984 that DLBD had been overlooked in European and American countries, several autopsied cases with DLBD were also reported in those countries. Furthermore, in 1990 I indicated in my review [17] of 36 autopsied DLBD cases reported in Japan that DLBD could be classified into two forms, a common form and a pure form, and that clinical features were different in the two forms. In the common form, the onset was usually older than 65 years (presenile or senile onset), and the chief symptom was cognitive impairment, followed by parkinsonism in 70 % of the cases, while no parkinsonism was detected in 30 % of the cases. On the other hand, in the pure form, the onset was usually much younger, and the initial symptoms were usually those of parkinsonism followed by dementia. Thereafter, when I was invited to the 150th Annual Meeting of the German Psychiatry Association, on the basis of a comparative study between Japanese and European-American autopsied cases with DLBD, I reported [18] that no apparent differences of the clinical features in the common form were present between the two groups, but that in the pure form, Japanese cases had much younger onset and Parkinsonism preceded dementia, while most European-American cases were of presenile or senile onset and dementia preceded parkinsonism. Perry et al. (1990) [19] proposed “senile dementia of Lewy body type,” and Hansen et al. (1990) [20] proposed the term “Lewy body variant of Alzheimer’s disease.” In 1995, the first International Workshop on DLB was held in Newcastle upon Tyne in England. At the workshop, the title of my lecture was “Diffuse Lewy body disease within the spectrum of Lewy body disease” [21]. It was at this International Workshop that “dementia with Lewy bodies” (DLB) was proposed [22]. The results of the Workshop were reported [23] in Neurology in 1996. Then, the clinical and pathological guidelines for DLB (CDLB guidelines) [23] were published, and the clinical diagnosis of DLB became possible. Thereafter, clinical studies were developed further.

The Second International Workshop on DLB was held in Amsterdam in 1998, and the results of the workshop [24] were published in 1999. The Third Workshop was again held in Newcastle upon Tyne in 2003, and the CDLB guidelines-Revised [2] were published in 2005. A symposium titled “A cross-road at DLB and PDD” was held in Washington in 2005, and the results [3] were published in 2007. In 2006, I held the forth International Workshop on DLB and PDD in Yokohama, Japan. Since 2007, I have held the Japan DLB Research Meeting in Yokohama every November. In the Second Japan Annual Meeting, I organized the DLB Family Association in Japan. In 2012, we published “Front Line of DLB Research in Japan” [25].

Over the last 18 years, many important reports on DLB have been published. For example, DLB has been reported to be the second most frequent dementia following AD [26]. Some biological markers for the clinical diagnosis of DLB have also been developed, such as brain SPECT/PET, dopamine transporter imaging [27] (FP-CIT SPECT or DaT scan), and MIBG myocardial scintigraphy [28]. Alpha-synuclein gene mutations [29–31] were found in familial PD and DLB in 1997 to 2004. Alpha-synuclein was defined to be the main component of Lewy bodies in 1997 [32]. Alpha-synuclein is a 149 kDa protein encoded by the SNCA gene, and it is rich in nuclei and presynaptic areas, but its function is not yet well understood. In 2000, alpha-synuclein-positive inclusions were produced in transgenic animals [33, 34]. Braak et al. [35] hypothesized that Lewy pathology initiates in the brain stem and propagates upward to the cerebral cortex. However, in the cerebral type of LBD [14], numerous Lewy bodies were found in the cerebral cortex; in spite of their only being a few in the brain stem nuclei, Lewy pathology was thought to occur in the cerebral cortex and to propagate downward to the brain stem. Lewy pathology might also start from Auerbach’s plexus of the lower esophagus [36] or the olfactory bulb [35, 37]. Recently, aggregation of alpha-synuclein might spread transcellulary throughout the brain in a prion-like way [38].

Since attempts to correlate Lewy body pathology to either neuronal cell death or severity of clinical symptoms have not been successful, the synaptic pathology [39] of alpha-synuclein aggregation in Lewy body disease has garnered more attention. For example, it was shown [39] that 90 % or even more of alpha-synuclein aggregates in DLB cases were located at the presynapses in very small deposits.

Some therapeutic trials of galantamine [40] and donepezil [41, 42] to DLB have been reported. In 2014, “Aricept” was, for the first time, recognized as the therapeutic medicine for DLB in Japan. Recently, PD, PDD, and DLB are usually called Lewy body disease [2, 3, 43] as we [1, 13] have used in 1980.

We expect that the mechanism of alpha-synuclein aggregation will be solved and that the effective therapy for LBD will be developed in the near future.