Psychiatric Aspects Of Dementia With Lewy Bodies

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DLB is characterized clinically by dementia, visual hallucinations, and fluctuating consciousness in addition to parkinsonism. Neuropathological characteristics include alpha-synucleinopathy, such as Lewy bodies and Lewy neurites in the brainstem, particularly the substantia nigra, subcortical structures, limbic cortex, and neocortex. Some amyloid deposition is also found in most patients. Neurochemically marked cholinergic deficits are reported in addition to a moderate nigro-striatal dopaminergic, and monoaminergic deficits have also been reported. It is estimated that at least 80% of DLB patients experience some form of neuropsychiatric symptoms (23), such as visual hallucinations, auditory hallucinations, delusions, delusional misidentification, and depression. These visual hallucinations are consistently reported to be more frequent in DLB than in AD, also in samples diagnosed at autopsy, and constitute one of the key diagnostic features of the disorder. Although rates vary from 25% to 83%, most prospective studies indicate a frequency of more than 50%. Delusions, including delusional misidentifications, are also common in DLB patients (frequency 13-75%). The rate reported for depression has varied from 14% to 50% in patients with DLB depending upon the study definition, with a frequency of major depression that is probably greater than 30%.

Sleep disturbances, such as insomnia and increased daytime sleepiness, are more common in DLB than AD (62), and are also pronounced in PD (63). REM sleep behavior disorder (RBD) is character ized by loss of normal skeletal muscle atonia during REM sleep with prominent motor activity and dreaming. RBD is particularly common in DLB (64). When associated with dementia or parkin-sonism, RBD usually predicts an underlying synucleinopathy, and it has been proposed that RBD should be included in the clinical diagnostic criteria for DLB (64). In PD, an association between RBD and visual hallucinations has been reported (65). Interestingly, during clonazepam treatment, which may improve RBD, the frequency of visual hallucinations decreased, suggesting a causal link between RBD and halucinations (65).

Autopsy studies have identified greater cholinergic deficits in the cortex of hallucinating patients when compared to nonhallucinating patients (66,67). A provisional report of a prospective clinico-pathological study (68) indicates an association between visual hallucinations and less severe neu-rofibrillary tangle pathology, the reverse association to that seen in AD, highlighting an important difference in the biological substrates of key neuropsychiatric symptoms in the two conditions. Recent neuropathological studies have also indicated a significantly higher number of Lewy bodies in the temporal cortex of DLB patients with visual hallucinations compared to those without (60). Neuroimaging studies using SPECT (single photon emission computed tomography) report reduced blood flow to the primary visual areas in the occipital cortex as the main association of visual hallucinations (69). Delusions have been less studied, but were associated with increased muscarinic Ml receptor binding (70). One preliminary study has examined the neurochemical associations of depression, indicating that DLB patients with major depression had a relative preservation of 5HT reuptake sites, compared to those without (68). The associations of other neuropsychiatry features await evaluation.

In a direct comparison with PD and dementia, DLB and PD patients showed very similar profiles of neuropsychiatric symptoms, although the frequency of most symptoms was higher in DLB than in PD patients (59). The majority of DLB patients were diagnosed by autopsy, but the methods of assessing neuropsychiatry symptoms differed slightly in the two groups. In 93 DLB patients recruited to an international multicenter study of rivastigmine (24), neuropsychiatric symptoms were assessed using the NPI. On most items, a positive score was reported in more than 50% of the patients, except euphoria, disinhibition, and apathy. The highest frequency was found for hallucinations, depression, and anxiety (see Table 1) (Janet Grace & Ian McKeith, personal communication) (71), a pattern similar to that reported in PD. There was a trend toward higher NPI scores in patients with more cognitive impairment as measured with the Mini Mental State Examination (MMSE), and this was significant for the four-item NPI (the sum of hallucination, delusion, depression, and apathy items) (24). In summary, psychiatric symptoms, in particular visual hallucinations, are extremely common in DLB, and help distinguish these patients from patients with AD and other disorders (46), although DLB may be diagnosed also in the absence of visual hallucinations (72). The profile of neuropsychiatry symptoms, as well as the cognitive profile (73) in DLB patients are similar to the symptoms observed in PD patients.

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