Cognitive Impairment

Executive and visuospatial functioning are the domains most consistently impaired in DLB.³⁵ Symptoms of executive dysfunction include changes in problem solving, performance of sequential tasks, multitasking, and complex decision making. Difficulties with navigating in familial surroundings and problems sitting on a sofa or lying in the correct orientation on a bed are commonly voiced symptoms of visuospatial dysfunction. Memory impairment can vary from slight to very severe.³⁵ Verbal blocking, in which a person tends to lose the train of thought in the middle of a sentence, is very common; this phenomenon can be mistaken for dysarthria or aphasia. Apathy and bradyphrenia are also common. Misidentification errors involving people can occur and are particularly upsetting when patients fail to recognize their own spouses or children. Reflections in mirrors may be mistaken for other individuals, and patients may speak to or argue with the perceived person. Most clinicians have regarded these cognitive symptoms as reflecting dysfunction of the frontosubcortical and parieto-occipital neural networks, as well as cholinergic depletion.

Fluctuations—periods of time when cognition and arousal are near normal and other periods of more marked confusion or decreased alertness—are considered a defining feature of DLB.^6–8 The neural substrate responsible for fluctuations is not clear, but neurochemical alterations³¹ and sleep/wake dysregulation³⁶ have been proposed.

Neuropsychiatric Features

Another defining feature of DLB is the presence of visual hallucinations.^6,7,37 Often the hallucinations are first noted in the bedroom when the room is darkened at night; patients often visualize insects, animals, or people in the room, on the bed, or on the ceiling. These hallucinations are often vivid and fully formed, and patients often cannot be convinced that the stimuli are not truly present. In some, visual hallucinations can be frightening or can become the source of delusions (e.g., “That little girl has been stealing my money”). Visual illusions also are common and often coincide with the presence of visual hallucinations. Delusions are also frequent and typically have a paranoid quality, like the example just noted.³⁷ Capgras’ syndrome—the belief that a relative or friend (usually spouse) has been replaced by an identical-appearing impostor—is also a feature of DLB.³⁸ Depression occurs at some point in the illness in almost all patients with DLB, sometimes years before the onset of dementia.^6,37 Anxiety is also common. Auditory, tactile, or olfactory hallucinations can also occur. Agitation and aggressive behavior are more variable; when present, they can be challenging to manage. Hypomania and overt bipolar disorder features can evolve, but they are atypical insofar as the onset usually occurs in patients in their 50s or 60s.

The underlying cause of hallucinations, delusions, and agitation probably reflects dopaminergic dysfunction, and serotonin dysfunction is probably involved in depression, anxiety, and bipolar-type features. Rapid eye movement (REM) sleep/wakefulness dysregulation has also been proposed as a mechanism underlying visual hallucinations in Parkinson’s disease and psychosis, in which the dream imagery of REM sleep may invade wakefulness.³⁹ The same mechanism has been proposed to underlie hallucinations associated with DLB.^24,33,34 The fact that psychostimulants can sometimes ameliorate hallucinations and delusions, which is similar to what occurs in narcolepsy, supports this hypothesis.^24,33

Motor Dysfunction

Parkinsonism unrelated to dopamine antagonist exposure is another defining characteristic of DLB.^6–8 Signs and symptoms include masklike facies, stooped posture, shuffling gait, difficulty with fine motor skills, sialorrhea, tremor, and bradykinesia.⁴⁰ Tremor tends to be more symmetrical and related to postural/action, rather than the unilateral and predominantly at-rest tremor that is typical of Parkinson’s disease. Myoclonus can also occur, and when the clinical course is rapid, differentiation from Creutzfeldt-Jakob disease can be difficult. Many of these symptoms and signs result from reduced dopaminergic activity.

Sleep Disorders

REM sleep behavior disorder (RBD) is common in DLB (as well as in Parkinson’s disease with or without dementia and in multiple-system atrophy).22–27,^33,34,41,42 Patients appear to be acting out their dreams by screaming, swearing, punching, and kicking (Table 70-2).^23,24,34 The theme of the dream is remarkably consistent across patients, almost always involving chasing or attacking, and the patient is usually protecting himself or herself against aggressors rather than being the attacker. When the patient is awakened and able to recall the dream content, the description of the dream tends to match the behaviors that were exhibited. Injuries such as pulled hair, bruises, lacerations, and broken bones have been described in patients and their bed partners. RBD often begins years or even decades before any cognitive or motor symptoms develop, and therefore RBD may be the first sign of an evolving neurodegenerative disorder in many individuals. Excessive daytime somnolence, in which patients struggle to stay awake through the day, is also common.^43,44 Other sleep disorders in DLB include insomnia, obstructive sleep apnea, central sleep apnea, restless legs syndrome, and periodic limb movement during sleep.⁴² In one polysomnographic series of DLB patients, at least one sleep disorder was present in almost every case.⁴⁵ These sleep disorders are important to recognize because treatments exist for each one, and clinical improvement can be dramatic in some instances when all sleep disorders are effectively treated.

TABLE 70-2 Typical Clinical Features of REM Sleep Behavior Disorder

Rights were not granted to include this table in electronic media. Please refer to the printed book.

From Boeve B, Silber M, Ferman T, et al: REM sleep behavior disorder in Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. In Bedard M, Agid Y, Chouinard S, et al, eds: Mental and Behavioral Dysfunction in Movement Disorders. Totowa, NJ: Humana Press, 2003, pp 383-397.

Dysfunction in brainstem neuronal networks are believed to underlie RBD, particularly the pedunculopontine nucleus, locus ceruleus, and gigantocellularis reticular formation (see Fig. 70-3), although the specific networks have not been fully defined.^23,24 α-Synuclein–positive pathology is often present in the lateral hypothalamus, which could explain the hypersomnolence and narcolepsy-like features. Central sleep apnea syndrome is also probably caused by brainstem dysfunction. The specificity of these sleep disorders to LBD is still being studied, but at least for RBD, it occurs almost exclusively in the synucleinopathies and rarely in other neurodegenerative disorders.^23,24

Autonomic Dysfunction

Orthostatic hypotension, impotence, urinary incontinence, and constipation are common in DLB,^46–48 although the frequency of each feature in DLB has not been systematically studied. Lewy bodies have been found in the intermediolateral column of the spinal cord and in the sympathetic nerves in the thoracic and abdominal structures, which reflects the rather widespread nature of Lewy body pathology in the central and peripheral nervous systems.^47,49

Blood/Urine

The role of laboratory testing is most helpful in identifying treatable causes of cognitive impairment.⁵⁷ No specific findings on laboratory testing of blood or urine that are characteristic of DLB have been identified as yet.

Cerebrospinal Fluid Analysis

On cerebrospinal fluid testing, low Aβ42 and normal tau levels⁵⁸ have been reported in DLB, but this profile is also consistent with the diagnosis of Alzheimer’s disease. Hence, no specific findings on cerebrospinal fluid analysis that are diagnostic of DLB have been identified as yet.

Neuropsychological Testing

Neuropsychological testing typically reveals impairment on measures of attention/concentration and visuospatial functioning in DLB.^{13,35,59–61} Visuoconstructive abilities can be tested by having a patient draw a clock or copy the Necker cube, intersecting pentagons, and the Rey-Osterreith complex figure (Fig. 70-4). A similar pattern of deficits—impaired visual perceptual-organizational skills, constructional praxis, and verbal fluency—have been demonstrated in patients with dementia plus RBD.⁴¹ In a subsequent analysis in which the pattern of neuropsychological impairment was compared between one group of patients with RBD and dementia and another group of patients with autopsy-proved Alzheimer’s disease, a double dissociation was identified, in which the patients with RBD and dementia had worse impairment on measures of attention, visual perceptual-organizational skills, and letter fluency, whereas the patients with Alzheimer’s disease had had significantly worse performance on confrontation naming and verbal memory.²⁵ The same pattern was then found in a group of patients who had dementia and RBD but did not have parkinsonism or visual hallucinations.²⁶ These findings suggest that in the absence of visual hallucinations or parkinsonism, the presence of dementia and RBD may indicate underlying Lewy body disease. More recent neuropathological studies have corroborated this hypothesis.^23,24 These studies strongly support the role of neuropsychological testing in the differential diagnosis in patients with dementia.

Figure 70-4 Examples of visuoconstructive impairment in patients who have dementia with Lewy bodies: the Necker cube (A is correct template, B and C are abnormal), a clock (D to F are all abnormal), and a Rey-Osterreith complex figure (G is correct template, H and I are abnormal).