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INTRODUCTION

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Although Lewy body disease (LBD) was once conceptualized as a disease of the substantia nigra, modern human postmortem studies with alpha-synuclein immunohistochemistry revealed that Lewy body and Lewy neurite pathology most often begins in the enteric and autonomic nervous systems before ascending through the brainstem to the substantia nigra, limbic system, and ultimately the cerebral cortex. In other individuals, disease may begin in the olfactory bulb and spread inward through olfactory system connections. These sites of onset, positioned as they are at neural interfaces with the environment, have suggested to some that a toxic environmental exposure may trigger the disease. Individual patients vary in their adherence to these general patterns, and the tempo and topology of progression dictate the clinical syndrome. Some patients with long-standing Parkinson’s disease (PD) (Chap. 427) without cognitive impairment slowly develop a dementia that is associated with visual hallucinations and fluctuating alertness. In this scenario, the term Parkinson’s disease dementia (PDD) is often used. In other patients, dementia and a neuropsychiatric syndrome precede or co-emerge with the parkinsonism, and the patient is diagnosed with dementia with Lewy bodies (DLB).

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CLINICAL MANIFESTATIONS

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The DLB syndrome is characterized by visual hallucinations, parkinsonism, fluctuating alertness, neuroleptic sensitivity, rapid eye movement (REM) sleep behavior disorder (RBD), and often hyposmia and excessive daytime sleepiness. Delusions related to persecution, invasion, and person or place identity (reduplicative paramnesia) are common. Both PDD and DLB may be accompanied or preceded by symptoms referable to brainstem pathology below the substantia nigra including constipation, orthostatic lightheadedness, depression/anxiety, and RBD, and most researchers now conceptualize DLB and PDD as points on a spectrum of LBD pathology. When orthostatic hypotension is present, DLB must be distinguished from multiple system atrophy with parkinsonism (MSA-P) (Chap. 432). Recurrent, disabling syncope early in the course, accompanied by laryngeal spasms and anterocollis, suggest MSA-P. In DLB, orthostasis can appear early but rarely becomes disabling until well into the course, when neuropsychiatric symptoms and cognitive dysfunction are well-established.

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Patients with DLB and PDD are highly sensitive to metabolic perturbations, and in some patients the first manifestation of illness is a delirium, often precipitated by an infection, new medicine, or other systemic disturbance. A hallucinatory delirium induced by L-dopa, prescribed for parkinsonian symptoms attributed to PD, may likewise provide the initial clue to a DLB or PDD diagnosis. Conversely, patients with mild cognitive deficits and hallucinations may receive typical or atypical antipsychotic medications, which induce profound parkinsonism at low doses due to a subclinical LBD-related nigral dopaminergic neuron loss. Minor day-to-day variation in cognitive functioning is common across dementias, but in DLB fluctuations can be marked, with bouts of confusion, lethargy, or even stupor that may rapidly resolve. Cognitively, DLB features relative preservation of episodic memory but often more severe visuospatial and executive deficits than seen in patients with early stages of Alzheimer’s disease. Iodine-123-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy to illustrate cardiac postganglionic sympathetic denervation ...

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