A 67-year-old woman is brought to the office by her son. He reports that his mother has had periodic confusion, memory loss, and poor sleep and seems "kind of out of it sometimes." These symptoms have gradually worsened over the past 1-2 years. The patient occasionally sees "strangers in the backyard," who are not there when her son looks for them. More recently, she has begun walking more slowly and has fallen twice in the past month without any significant injuries. The patient has a history of hypertension and depression. She does not drink alcohol or use illicit drugs. On physical examination, she walks slowly and has mild bilateral hand tremors and mild bilateral lower limb rigidity. On cognitive examination, the patient appears to be oriented to person and place, and can recall 1 of 3 items in 5 minutes; she can state the days of the week forward but does not cooperate with stating them backward. Chemistries, complete blood count, vitamin B12, and thyroid function tests are normal. Serum treponemal test is nonreactive. MRI of the brain shows mild generalized cortical atrophy. Which of the following is the most likely diagnosis in this patient?
This patient's 1- to 2-year history of periodic confusion accompanied by visual hallucinations and parkinsonian motor symptoms (eg, tremors, rigidity) is suggestive of dementia with Lewy bodies (DLB), the cause of 10%-20% of dementias in the United States. DLB is characterized by alterations in consciousness, fluctuations in cognition, visual hallucinations, parkinsonism, and relatively early compromise of executive functions. Repeated falls and sleep disturbance are characteristic.
At autopsy, Lewy bodies, eosinophilic intracytoplasmic inclusions representing accumulations of alpha-synuclein protein, may be seen in neurons of the substantia nigra, locus coeruleus, dorsal raphe nucleus, and substantia innominata. Pharmacotherapy of DLB consists of carbidopa-levodopa for parkinsonism and cholinesterase inhibitors for cognitive impairment. If psychotic symptoms persist, a low-dose second-generation antipsychotic, rather than a first-generation antipsychotic, is preferred due to the severe neuroleptic sensitivity seen in these patients.
(Choice A) Alzheimer disease typically presents with early and prominent memory loss. The core clinical features of cognitive fluctuations, visual hallucinations, and parkinsonism in this patient make DLB more likely.
(Choice C) Major depressive disorder is characterized by persistent depressed mood and syndromal neuro-vegetative symptoms. Although mild cognitive impairment and psychotic features can occur in major depression, this patient's parkinsonism and fluctuating cognition would not be consistent with depression.
(Choice D) Normal-pressure hydrocephalus is characterized by cognitive changes (eg, decreased attention and concentration, apathy), changes in gait, and urinary incontinence. Visual hallucinations and sleep impairment are not common. MRI characteristically shows ventriculomegaly that is out of proportion to the degree of sulcal widening.
(Choice E) Lewy bodies are a pathologic finding also present in Parkinson disease. The key distinction between these 2 conditions is the early appearance of cognitive fluctuations and dementia in DLB, whereas dementia occurs late in the course of Parkinson disease (much later than the emergence of motor symptoms). In addition, visual hallucinations are not common in Parkinson disease unless they are due to dopaminergic medications given to treat the underlying illness.
Educational objective:
Dementia with Lewy bodies causes cognitive fluctuations, visual hallucinations, and parkinsonism. Cognitive symptoms may precede, or appear along with, parkinsonian features.