Behavioral and psychological symptoms of dementia (BPSD) in dementia with Lewy bodies
This review article was presented by the author in Symposium of the 22nd Annual Meeting of Japanese Psychogeriatric Society in Osaka, 15-16 November 2007.
Dr Kenji Kosaka MD PhD, HouYuu Hospital, 644 Kanegaya, Asahi-ku, Yokohama 241-0812, Japan. Email: email@example.com
Behavioral and psychological symptoms of dementia (BPSD) bother patients with dementia with Lewy bodies (DLB) and their families so frequently that early diagnosis of DLB before the appearance of prominent cognitive impairment is important. Because BPSD in DLB can be reduced or improved by early intervention, medical intervention is important. Of BPSD in DLB, vivid visual hallucinations and delusions are most important. Other visual cognitive impairments and sleep disturbances, including disorders in rapid eye movement (REM) sleep, are also frequently seen. Cholinesterase inhibitors, including donepezil chloride, are the first choice for the therapy of BPSD; Yokukansan (a type of Kanpo (traditional Chinese herbal) medicine) is the second choice. When neither treatment is effective, atypical antipsychotics, such as quetiapine, risperidone, and aripiprazol, may be used.
In dementing illnesses, the central symptom is cognitive impairment and the surrounding symptoms are usually called behavioral and psychological symptoms of dementia (BPSD). These BPSD are the most troublesome for caregivers of demented patients and can be classified into two groups: (i) symptoms that are disclosed following interviews with patients and/or their caregivers, such as delusions, hallucinations, anxiety and depression; and (ii) symptoms recognized following observation of patients' behavior, such as wandering, psychomotor excitement, agitation and negativism.
Dementia with Lewy bodies (DLB) is now the second most frequent dementia following Alzheimer's disease and is frequently accompanied by BPSD. The present paper focuses on BPSD in DLB.
PAST AND PRESENT STATUS OF DLB
From 1976 to 1979, there were three Japanese1,2 and two German3 reports of autopsied cases showing progressive dementia and parkinsonism characterized pathologically by the presence of numerous Lewy bodies in the cerebral cortex and amygdala, as well as the brain stem nuclei and diencephalon. In 1980, the term ‘Lewy body disease’ was proposed,4 with identification of three distinct types: (i) a diffuse type; (ii) a transitional type; and (iii) a brain stem type. Our concept of Lewy body disease was as follows:
Lewy body disease is a chronic progressive neuropsychiatric disease characterized clinically by idiopathic parkinsonism of presenile or senile, but occasionally of younger onset, with or without dementia. In some cases progressive dementia and/or Shy–Drager syndrome precedes parkinsonism. The main neuropathological features are characterized by the presence of numerous Lewy bodies in the central and sympathetic nervous system.2
Furthermore, in 1984 the term ‘diffuse Lewy body disease (DLBD)’ was proposed5 based on 11 autopsied cases. Diffuse Lewy body disease is a clinicopathological disease entity characterized clinically by progressive cortical dementia and parkinsonism of presenile or senile, but rarely of younger, onset. Neuropathologically, DLBD is characterized by the presence of numerous Lewy bodies in the cerebral cortex and amygdala, as well as in the brain stem nuclei and sympathetic ganglia. In 1990, DLBD was divided into two categories on the basis of the presence or absence of Alzheimer pathology:6 (i) a common form; and (ii) a pure form.
In 1996, the term DLB was proposed by the DLB Consortium.7 For the first time, clinical and pathological diagnostic criteria were defined. Revised guidelines for the diagnosis of DLB were published in 2005.8 Recently, there has been some discussion as to whether DLB and Parkinson disease dementia (PDD) are the same entity. Considerable evidence has been collected to support the notion that DLB and PDD are the same. The reports published by both the DLB Consortium8 and the DLB/PDD Working Group9 indicate that PDD and DLB may be understood within the spectrum of Lewy body disease. Since 1980, we have insisted that Parkinson's disease, PDD and DLB should be understood within the spectrum of Lewy body disease.4,10 This is now being widely been recognized.
BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA IN DLB
According to the revised DLB diagnostic criteria,8 visual hallucinations, hallucinations in other modalities, delusions, rapid eye movement (REM) sleep behavior disorders (RBD) and depression are manifestations of BPSD in DLB.
Visual hallucinations are quite characteristic and involve images of persons or small animals, which are vivid, colorful, formed, detailed, and rapidly moving. In addition, other visual cognitive impairments,11 such as visual illusions, metamorphopsia, duplicated paramnesia, ‘lebhaftige Bewusstheit’, and personal or topographical misidentification, are seen occasionally. Capgras' syndrome, Fregoli's syndrome, and nurturing syndrome12 are rarely noted. Auditory hallucinations and somatosensory hallucinations occur occasionally. Delusions of persecution or jealousy frequently occur, usually secondary to visual and/or auditory hallucinations. Because this type of hallucinatory–delusional state is prominent at the early stage without apparent cognitive impairment, patients are frequently misdiagnosed as having senile psychosis or late paraphrenia. It is apt to be suggested by the finding that brain atrophy is mild on computed tomography or magnetic resonance images. A depressive state is frequently seen during the early stages of DLB. In addition, RBD is frequently detected during the very early or early stage of DLB.
EARLY DIAGNOSIS AND THERAPY FOR BPSD IN DLB
The above-mentioned BPSD in DLB bother caregivers and patients so frequently that the early diagnosis of DLB is important, because the BPSD can be reduced or improved by early intervention. Cognitive impairment is often not prominent during the early stage of DLB. Therefore, it is better to diagnose DLB early when cognitive impairments are still at the level of mild cognitive impairment (MCI). The diagnosis of DLB should be considered on the following occasions: when characteristic visual hallucinations are marked; when RBD is prominent; when senile depression is followed by cognitive impairment; when dementia occurs during the course of Parkinson disease; when occipital hypoperfusion is present on single photon emission computed tomography (SPECT); or when meta-iodobenzylguanidine (MIBG) uptake is disturbed in MIBG myocardial scintigraphy.
As for the medication used to treat BPSD in DLB, the first choice is donepezil chloride (in Japan, donepezil is the only cholinesterase inhibitor available). Donepezil has been reported to be effective in the treatment of BPSD in DLB.13 The second choice is Yokukansan (a type of Kanpo (traditional Chinese herbal) medicine): Yi-Gan San.14 Yokukansan has received considerable attention in Japan as a treatment for BPSD in DLB. At present, wide multi-institutional clinical trials are underway to determine the effectiveness of Yokukansan in the treatment of BPSD in DLB. The third choice for therapy is atypical antipsychotics, including risperidone, quetiapine, aripiprazol, perospirone, and olanzapine. Serotonin–norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) are routinely used for the treatment of depression.