A 72-year-old right-handed piano teacher is admitted to the hospital for a fractured left hip, agitation and confusion. Her children report that she fell while chasing imaginary figures that she said entered through a window and threatened to kill her. For the past two years, the patient has had trouble finding her way in a familiar environment and has not been able to perform activities of daily living or attend to her finances. Her family has noted daily fluctuation in her mental status: She seems clearer in the morning than in the evening and has “bad days” and “good days.” On good days, she is able to attend to some chores and is oriented to the location of her house and at least the month and/or season and current year.
The patient walks slowly with a shuffled gait, stiffness and stooped posture. Family members report that her sleep pattern is often disrupted. She has a history of well-controlled hypertension, does not drink alcohol or use illicit drugs, and has no history of psychiatric disease. Her physical exam reveals the hip fracture as well as axial rigidity and slowed mobility. There is no tremor. She is afebrile and normotensive. Laboratory studies, including complete blood cell count, metabolic panel, fasting lipid profile, thyroid-stimulating hormone, B12 and folate, show no abnormalities. Her toxicology screen is negative. Brain MRI shows mild periventricular white matter changes but no acute stroke or hemorrhage.
On the hospital floor, after surgery to repair her hip, the patient becomes more agitated. Neuroleptics to decrease agitation produce a “shock reaction”; she becomes profoundly stiff and immobile, and the agitation remains unchanged. The orthopedic service asks for a neuropsychiatry consult to address the patient's behavior, which is compounding her altered baseline mental status.
What is the diagnosis?
The patient exhibits signs of agitation on a baseline mental status exam, and physical exam results are consistent with dementia with parkinsonism. Her normal lab results and normal brain MRI have ruled out delirium and stroke. She is suffering from a neurodegenerative disorder with chronic onset of at least two years. The agitation is aggravated by the recent fall. Dementia with Lewy body (DLB) is the leading working diagnosis.
DLB is clinically similar to—and may in later stages be indistinguishable from—Parkinson's disease with dementia (PDD). The “one-year rule,” the current standard used to differentiate the two, states that DLB presents with dementia within a year of diagnosis of parkinsonian symptoms while PDD presents years after the diagnosis of Parkinson's has been well established. Other features in this patient's presentation that are consistent with DLB are formed visual hallucinations, fluctuating mental status, sleep disturbances and abnormal response to the “neuroleptic challenge.” DLB is now thought to be the second most common type of neurodegenerative dementia after Alzheimer's disease. There is a substantial overlap in the pathology of Alzheimer's disease and DLB.
What causes the psychosis accompanying DLB?
Seventy-five percent of patients with DLB present with visual hallucinations at the onset of their disease, and more than 50% of them have delusions (Int J Geriatr Psychiatry. 2001; 16:528-536). DLB symptoms are thought to be directly related to the deposition of alpha-synuclein protein, the major component of the Lewy body, in the substance of the brain. This protein deposition, which causes the neurodegeneration, starts first in the brainstem and moves upward to reach all levels of the cortex (Neurology. 2007; Mar 13;68:812-9).
Patients with DLB-related psychosis generally fall into two categories. Patients in the first group, who present with mild visual-perceptual illusions, may retain some insight into the hallucinations and generally do not find them troubling. Patients in the second group present with complex psychotic paranoid and persecutory delusions accompanied by threatening visual hallucinations, usually after a year of disease progression. These patients lack insight and feel compelled to respond to their hallucinations. Increasing agitation and confusion could be the first presenting symptoms. DLB patients may also experience Capgras syndrome, characterized by delusional misidentification of friends and family as strangers or impostors.
What leads to sleep disturbances in DLB?
In patients with DLB, vivid perceptions and illogical thinking in dreams affect REM sleep, causing typically REM sleep disorders. Patients with REM sleep disorders lose the physiological paralysis of muscles during dream states and start “acting out” their dreams. DLB patients tend to experience more hallucinations when falling into or waking up from sleep, causing increased agitation.
Are there any special tests to assess DLB?
A clinical diagnosis of DLB is based on a history of visual hallucinations; mental status changes; delusions; sleep disorders; and exam results revealing rigidity, stooped posture, and gait instability (Mov Disord. 2007; Jun 15;22:1061-8). Tremors may be present. It is always helpful for the physician to confer with an outside observer, caregiver or both to corroborate the patient's history and symptoms. Although neuropsychological testing is clinically helpful to ascertain the diagnosis, it is not imperative to get a neuropsychological battery. Clinical experts recommend first ruling out any cause of concomitant delirium or stroke and providing close clinical follow-up. When in doubt, and if mental status and behavior have deteriorated rapidly, a neuropsychological testing battery may be helpful.
How should this patient be treated?
The patient's medications should be simplified as much as possible to decrease side effects and drug-drug interactions. As is often the case in patients with DLB and PDD, the treatment plan may include reducing dopamine agonists and stopping any dopamine blockers, as they may be causing or aggravating the clinical deterioration. The use of conventional neuroleptics is not indicated because many reports have linked these agents with rapid deterioration of motor skills and an increase in parkinsonism.
Atypical neuroleptics may be tried. The physician should remember that DLB patients show sensitivity to dopamine blockers. Until recently, DLB diagnoses were clinically confirmed by challenging DLB patients with neuroleptics and documenting worsened presentation. Aripiprazole, olanzapine and quetiapine have been shown to have minimal or no efficacy in DLB, while clozapine has been shown to be somewhat effective. Practically, however, many physicians first prescribe quetiapine or olanzapine because clozapine must be strictly regulated with weekly tests of blood cell counts for safety reasons.
Cholinesterase inhibitors are now used to treat DLB-related psychosis. From a cognitive standpoint, and backed by pathological specimens, there is evidence that the Lewy bodies are present along the cholinergic pathway, including the nucleus of Meynert, affecting cholinergic systems in DLB (Neurology. 2007 Mar 13;68:812-9). Donepezil and rivastigmine have shown some effectiveness (N Engl J Med. 2004 Dec 9;351:2509-18); the latter is FDA approved for the treatment of dementia with parkinsonism symptoms.
In addition to medication, this patient's physician should try to lessen her agitation by providing her with a sitter, ideally a family member or someone she knows, during her hospital stay. All efforts should be made to shorten her hospital stay so she can return home. The social work team on the inpatient service can help facilitate the transition and contact in-home or placement services. Follow-up for this patient should focus on making her comfortable and educating her family and caregivers about DLB by addressing the fluctuations in her mental status and how they will affect her everyday life.
After medication options are considered, the patient is started on 1.5 mg of rivastigmine twice daily. To minimize possible gastrointestinal distress, rivastigmine is given with meals and the dose is slowly increased until it reaches 6 mg per day. A switch to a rivastigmine patch was considered six months after hospitalization. The cholinesterase inhibitor did not alter her cardiac rhythm, as documented by an EKG during a follow-up visit with her primary care physician. With the help of the hospital's social work team, community and residence services are set up. She also was referred for long-term neurological care at a memory disorder unit.
Although we have made strides toward understanding the pathology of PDD and DLB and the psychosis related to these diseases, additional research on prevention, early detection, treatment and patient and caregiver services is needed. A sensible treatment plan will only be successful if it examines all aspects of the disease and addresses simultaneously its effects and its burden on patients and their caregivers.