Dementia with Lewy Bodies: Parkinsonism and Dementia in an Older Man
Dementia with Lewy bodies (DLB) is either the second or third most common cause for dementia in the economically developed world,1 yet it is frequently not recognized. While it is often mistaken for Alzheimer’s disease (AD) early in the course because the parkinsonian features frequently develop after the dementia has begun, making the correct diagnosis leads to better management. The development of parkinsonism in a person with dementia not taking neuroleptics or on very low doses should always raise this consideration,2 but other signs and symptoms often point to the correct diagnosis.
A 78-year-old, right-handed man was referred to a movement disorders clinic for evaluation of parkinsonism. The patient had been having memory problems for approximately five years. Three years after his memory problems first began, he was diagnosed with AD and was started on donepezil with mild benefit. Approximately 18 months before this evaluation, he began developing slowly progressive walking problems, with short steps and slowness. As his gait worsened, the patient developed a walking problem that propelled him, sometimes causing him to run or walk on the balls of his feet despite using a cane. His wife noted that he had difficulty judging distances and would often nearly miss a chair when sitting down. Approximately six months ago, he began having visual hallucinations of deceased family members. For an unknown period of time, he has had severely impaired smell and taste, and has had multiple episodes of becoming unresponsive, lasting up to 10 minutes, without focal deficits or seizure activity noted, occurring when seated. He did not have behaviors suggestive of rapid eye movement sleep behavior disorder (RBD). His wife noted that his level of confusion varies during the day. At times, the patient cannot identify family members or his best friend, whereas at other times, he has only minor memory problems.
The patient had been evaluated for his unresponsive episodes, and a heart pacemaker was implanted for a presumed bradycardic explanation, but it was unhelpful. He denied feeling lightheaded on standing, but had been treated with fludrocortisone, without reduction in unresponsive spells. Although electroencephalograms revealed no epileptic activity, the patient was placed on lamotrigine, with uncertain benefit. His wife had stopped calling emergency services when the patient became unresponsive, choosing to let him recover at home. Following each spell, he slept much of the day but recovered to baseline.
There was no history of alcohol or substance abuse or any recent use of nonprescribed drugs. His history was positive for hypertension, hypercholesterolemia, and orthostatic hypotension. He had a brain magnetic resonance imaging (MRI) scan five years prior that reportedly showed “mini-strokes,” and he was reported to have had transient ischemic attacks, but details were not available. There was no family history of Parkinson’s disease (PD), AD, or other neurological disorders.
His medications included solifenacin 5 mg daily, simvastatin 40 mg daily, clopidogrel 75 mg daily, memantine 10 mg twice per day, metoprolol 25 mg daily, lisinopril 10 mg daily, hydrochlorothiazide 12.5 mg daily, lamotrigine 200 mg daily, fludrocortisone 0.15 mg daily, and donepezil 10 mg daily. He had not been on dopamine receptor-blocking drugs.
On examination, the patient was a thin, athletic-appearing man who knew his age but not the month, season, or year. Although he had watched a ball game the previous night, he could not recall the visiting team. His naming was impaired, although his speech was fluent, without paraphasias or pauses for word-finding. Cranial nerves were normal. His motor exam was remarkable for a positive right Babinski’s reflex and the following: akinesia; bradykinesia, which was worse on the left; and a gait typical of parkinsonism, with small steps, flat foot strike, severely reduced arm swing, and turning en bloc. His balance was preserved. Sensory exam was normal. The brain MRI was not repeated.
By expert consensus definition, probable DLB is present when a patient with dementia has two of three of the following features: parkinsonism; visual hallucinations; and fluctuating level of cognition. A supportive feature is syncope or episodes of unresponsiveness.2 The prevalence of DLB is not well known due to problems with diagnosis. Postmortem studies of patients with dementia have shown that 40% had Lewy body pathology consistent with the diagnosis of DLB, but many were diagnosed in life with AD. 3,4
Cognitive fluctuations are a hallmark feature of DLB2 and are surprisingly uncommon in AD.5 Patients may seem quite intact at one time and quite demented at others. In this case, the case patient sometimes could not identify his life-long best friend, while at other times, he could reminisce appropriately. The visual hallucinations in DLB are identical to those that occur in people with PD who take medications for their motor disability.6 These are primarily visual, but auditory as well. The auditory hallucinations may be distinct from the visual or may be associated with them.
The visual hallucinations are usually people or animals but may be inanimate objects such as statues or pieces of furniture. They are usually without emotional content, so that a patient seeing a dead relative will usually not be happy or alarmed. The auditory aspect may occur with a visual hallucination talking or might be unrelated, as with hearing party sounds from another room or indistinct voices.
The parkinsonism of DLB may look exactly like idiopathic PD but, in general, tends to have less tremor and to be less responsive to PD medications.1 Because dementia is a risk factor for delirium and psychotic symptoms from PD drugs, patients with DLB are at high risk for iatrogenic behavioral complications.
Extreme neuroleptic sensitivity is one of the central features of DLB,2 but whether patients with DLB are more sensitive than other patients with parkinsonism is unknown. Quetiapine7 is well tolerated by all patients with parkinsonism with dementia, but its efficacy has not been established. Since psychotic symptoms, particularly hallucinations, are common, it is important to recognize that all antipsychotic drugs, excepting only quetiapine and clozapine, may produce parkinsonism in normal people and worsen parkinsonism in those who already have it, particularly in patients with DLB.8
Episodes of unresponsiveness are not well described in DLB. These are usually ascribed to autonomic dysfunction.1,2 In my experience, families of patients with DLB report spells lasting from a few minutes to an hour or more, in which the patients may appear asleep with their eyes open. They are difficult to rouse or may be unarousable, with no focal findings, and when seen in the hospital all vital signs are normal. Spells occur with a frequency that varies from none to a few times per week.
Olfaction is impaired in the great majority of persons with DLB and PD, and is usually present before any motor features point to the diagnosis. This sensory deficit is not specific to Lewy body disorders and may be seen in AD as well as numerous other conditions.
Early in its course, DLB may be indistinguishable from AD1 as with the case patient. In general, DLB probably affects men more than women,9 although the data are uncertain,10 whereas AD is more common in women.1 There are differences between the two disorders on neuropsychological testing,11 although these are not completely reliable in distinguishing the two disorders.12 Patients with DLB tend to have more psychiatric problems early on. Hallucinations, for example, are three times more common in pathologically proven DLB than AD.12 RBD is highly indicative of a disease involving synuclein, which translates to DLB in a patient with dementia and no parkinsonian stigmata yet apparent,13 as it is rare in AD and other dementias. However, RBD is present in only a minority of men and a much smaller percentage of women. AD causes a “cortical” dementia, in which there is early impairment of language function and praxis, whereas DLB causes a “subcortical” or “frontal” dementia with preservation of cortical function but reduced executive function,14 visual spatial deficits, 15 and a much larger fluctuating level of attention. Early in the course, the standard test battery, the Mini-Mental State Examination, which was developed for AD, frequently underestimates the degree of impairment in subcortical dementias.1,16
When the cardinal features of the disorder are present, as described in the most recent consensus definition of the disease,2 the specificity of diagnosis is very high.17,18 Sensitivity, however, when these cardinal features are not present, is not very good. It is unclear how much of the difficulty in making accurate diagnoses stems from the problem of mixed pathology usually found at autopsy, with plaques and tangles present in addition to cortical Lewy bodies.17-19 In the above case, by the time the patient was seen by a neurologist in the movement disorders clinic, the cardinal features were all present.
Although parkinsonism is seen in advanced AD, it is not common in early AD and is not associated with the sense of propulsion that the case patient described. As with this patient, however, the absence of tremor and the relative symmetry is typical. Parkinsonism is also a “usual” aging phenomenon that develops in presumably normal elderly people.20 Although the case patient had a language problem, indicative of cortical dysfunction, this may occur both in DLB and AD, although less common in DLB until the disease is advanced.
The diagnosis of DLB was made based on parkinsonism developing in a patient with dementia, visual hallucinations not induced by a psychoactive drug, fluctuating level of cognition, and episodes of unresponsiveness, thus meeting the consensus criteria proposed by McKeith et al2 for DLB.
The role of strokes in this case and other cases is usually uncertain. Unlike clinical stroke syndromes, where a patient seeks medical attention when a new deficit is apparent, people with advanced neurological disorders lose compensatory mechanisms as they lose brain volume, and thus develop such nonfocal findings as worsened dementia. The case patient had one positive Babinski’s reflex, suggesting that he probably had had at least one stroke affecting the corticospinal tract, and may have had other subclinical strokes, contributing to his dementia.
There is debate within the neurological community as to whether DLB is the same as Parkinson’s disease dementia (PDD). Currently, dementia that develops in a patient with PD one year or more after the motor dysfunction is considered PDD. If the dementia precedes the motor dysfunction or develops within one year of it, then the diagnosis, by consensus, is DLB.2 These are obviously arbitrary criteria but reflect our current conceptualization of the disorders. Whether the dementia precedes or follows the motor dysfunction does not alter management, other than that the presence of dementia limits how aggressively one can treat the motor symptoms, due to the greater likelihood of behavioral medication side effects in the patient with dementia. The dementia is believed to respond similarly to AD,21 and psychotic symptoms such as the visual hallucinations can safely be treated with quetiapine or clozapine,22 although efficacy is less clear.
DLB is common and often not recognized as distinct from AD. The treatments for the cognition and behavior are similar to what are used in AD21; however, physicians are often unaware of differences in other aspects of managing DLB cases. The value of knowing the diagnosis lies in knowing the following: the parkinsonism may be treatable, but the response is usually less satisfactory than in PD and with greater risk of drug-induced psychotic symptoms; the use of antipsychotic drugs is highly likely to exacerbate motor function unless either quetiapine or clozapine is used22; and the episodes of unresponsiveness are highly likely to be due to the disease, so that after repeated unrevealing evaluations, the family should be reassured that the spells are transient, resolve without intervention, and should be ascribed to the DLB itself, obviating the need for repeated testing and treatment trials.
The author reports that he has received speaker honoraria from GlaxoSmithKline, Boehringer Ingelheim, and Teva; is a consultant/paid advisory board member for Acadia Pharmaceuticals and EMD Serono; and has received research grants from Cephalon, Acadia Pharmaceuticals, Teva, Boehringer Ingelheim, and EpiVax.
Dr. Friedman is Director of the Movement Disorders Program of Butler Hospital, and Professor and Chief, Division of Movement Disorders, Alpert Medical School of Brown University, Providence, RI.
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