Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is a clinicopathologically heterogeneous dementia with features that overlap Alzheimer's disease (AD) and Parkinson's disease (PD).^1-3 DLB is defined pathologically by the presence of cortical Lewy bodies, although most cases have concomitant histopathologic markers of AD (primarily amyloid plaques). Autopsy studies have observed cortical Lewy bodies in 10 to 30% of all dementia cases, making DLB the second most common form of dementia behind AD.

Consensus guidelines for the clinical diagnosis of DLB highlight three core features: fluctuating attention, recurrent visual hallucinations, and parkinsonian motor features.³ Fluctuating attention confusional state and may be associated with hypersomnolence. Visual hallucinations in DLB are often florid, whereas extrapyramidal features are typically less severe than they are in PD and may include prominent gait disturbance.² The combination of psychosis and extrapyramidal features can be problematic because DLB patients may be exquisitely sensitive to the side effects of antipsychotic agents.

Preliminary observations suggest that DLB patients may particularly benefit from cholinesterase-inhibitor (AChE-I) therapy.^3,4 We describe two patients with DLB with prominent psychotic symptoms and fluctuating levels of consciousness or attention, reflecting two core features of DLB, who responded dramatically to treatment with the AChE-I donepezil.

Case reports. Patient 1. A 76-year-old man gradually developed a shuffling gait and intermittent confusional episodes. Normal-pressure hydrocephalus was diagnosed, but shunt placement had no effect. He subsequently developed florid visual hallucinations, paranoid delusions, and hypersomnolence, marked by going to bed 4 hours earlier than his previous habit and increasing his nap frequency from one to several per day. "Mr. Spook," a delusional entity, would hide under his bed every night, and on several occasions he ran out of the house to admonish nonexistent children he "saw" from playing in the street. During one of many recurrent episodes of unexplained confusion he received risperidone (0.5 mg) and became obtunded, precipitating a hospital admission.

Workup included a brain MRI, which showed moderate ventricular enlargement. CSF analysis of a shunt tap demonstrated adequate shunt function. Vitamin B₁₂, folate, rapid plasma reagin (RPR), and thyroid function tests were unremarkable. EEG showed generalized slowing, maximal over the right hemisphere.

Before starting donepezil his Mini-Mental State Examination (MMSE) score was 27/30. One month later on donepezil, his psychotic symptoms and hypersomnolence had abated, although his MMSE score was unchanged. At 6 months follow-up, he was stable clinically and showed slight improvement on the MMSE (28/30). His handwriting improved markedly over this time. At 1 year follow-up on donepezil, he remained free of any acute confusional episodes.

Patient 2. A 78-year-old man presented with a 5-year history of episodic fluctuations/alterations in level of consciousness, prominent visual hallucinations, gait impairment, bradykinesia, limb rigidity, and excessive somnolence (sleeping up to 20 hours per day). During one of several hospitalizations for an acute deterioration in his cognitive status and agitated psychosis, he became unresponsive after receiving haloperidol (1 mg). Workup included a brain MRI, thyroid function tests, B₁₂, folate, and RPR, which were all unremarkable. EEG showed mild diffuse slowing.

When DLB was diagnosed clinically, donepezil treatment was initiated. At that time, pervasive somnolence precluded formal testing. After 1 month on donepezil, he was fully alert and had a bright affect. He engaged easily in conversation and scored 23/30 on the MMSE. Delusions and agitation were markedly reduced, hallucinations had resolved, and he was sleeping 8 to 10 hours a day. At 1-year follow-up on donepezil, he had no subsequent episodes of acute fluctuations in cognitive status, maintained a normal sleep pattern, and exhibited mild residual delusional symptoms without any reported episodes of frank psychosis.

Discussion. Although lacking pathologic verification, the prominent psychotic disturbances and fluctuating deficits in attention (including hypersomnolence) evident in both patients represent core features of DLB.³ The link to DLB is strengthened by the presence of neuroleptic sensitivity in both patients and the resemblance of their primary symptoms to anticholinergic delirium⁵ because DLB patients have even greater cholinergic deficits than do AD patients.⁶ The resolution of hallucinations in these patients is consistent with observations that AChE-I therapy has a beneficial effect on such symptoms in AD.⁷ Although these two cases must be interpreted with caution, as the generalizability of these findings is unknown, the response of delirium-like features to AChE-I therapy supports the rationale for further investigations into the use of such agents in DLB.