Evidence-Based Reviews

Differentiating Alzheimer’s disease from dementia with Lewy bodies

Current Psychiatry. 2012 November;11(11):22-30

References

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Neuropsychiatric features. DLB patients are more likely than AD patients to exhibit psychiatric symptoms and have more functional impairment.¹⁸ In an analysis of autopsy-confirmed cases, hallucinations and delusions were more frequent with Lewy body pathology (75%) than AD (21%) at initial clinical evaluation.¹⁸ By the end stages of both illnesses, the degree of psychotic symptoms is comparable.¹⁹ Depression is common in DLB; whether base rates of depressed mood and major depression differ between DLB and AD is uncertain.²⁰

Psychosis in AD can be induced by medication or delirium, or triggered by poor sensory perceptions. Psychotic symptoms occur more frequently during the moderate and advanced stages of AD, when patients present with visual hallucinations, delusions, or delusional misidentifications. As many as 10% to 20% of patients with AD experience hallucinations, typically visual. Delusions occur in 30% to 50% of AD patients, usually in the later stages of the disease. The most common delusional themes are infidelity, theft, and paranoia. Female sex is a risk factor for psychosis in AD. Delusions co-occur with aggression, anxiety, and aberrant motor behavior.

Visual hallucinations—mostly vivid, well-formed, false perceptions of insects, animals, or people—are the defining feature of DLB.²¹ Many patients recognize that they are experiencing visual hallucinations and can ignore them. DLB patients also may experience visual illusions, such as misperceiving household objects as living beings. Delusions—typically paranoid—are common among DLB patients, as are depression and anxiety.¹ Agitation or aggressive behavior tends to occur late in the illness, if at all.

Clinical Point

Visual hallucinations, usually well-formed perceptions of insects, animals, or people, are the defining feature of DLB

The causes of psychotic symptoms in DLB are not fully understood, but dopamine dysfunction likely is involved in hallucinations, delusions, and agitation, and serotonin dysfunction may be associated with depression and anxiety. Rapid eye movement (REM) sleep/wakefulness dysregulation, in which the dream imagery of REM sleep may occur during wakefulness, also has been proposed as a mechanism for visual hallucinations in DLB.²² In DLB, psychotic symptoms occur early and are a hallmark of this illness, whereas in AD they usually occur in the middle to late stages of the disease.

Clinical Point

Compared with AD patients, DLB patients are at higher risk of developing extrapyramidal symptoms

Motor symptoms. In AD, extrapyramidal symptoms (EPS) are common later in the disease, are strongly correlated with disease severity, and are a strong, independent predictor of depression severity.²³ EPS are more common in DLB than in AD²⁴ and DLB patients are at higher risk of developing EPS even with low doses of typical antipsychotics, compared with AD patients.²⁵

Other symptoms. REM sleep behavior disorder (RBD) is characterized by enacting dreams—often violent—during REM sleep. RBD is common in DLB and many patients also have excessive daytime somnolence. Other sleep disorders in DLB include insomnia, obstructive sleep apnea, central sleep apnea, restless legs syndrome, and periodic limb movements during sleep.

Clinical Point

REM sleep behavior disorder, characterized by enacting often violent dreams, is common in dementia with Lewy bodies

In AD patients, common sleep behaviors include confusion in the early evening (“sundowning”) and frequent nighttime awakenings, often accompanied by wandering.²⁶ Orthostatic hypotension, impotence, urinary incontinence, and constipation are common in DLB. Lack of insight concerning personal cognitive, mood, and behavioral state is highly prevalent in AD patients and more common than in DLB.

Diagnostic evaluation

Because there are no definitive clinical markers for DLB, diagnosis is based on a detailed clinical and family history from the patient and a reliable informant, as well as a physical, neurologic, and mental status examination that looks for associated noncognitive symptoms, and neuropsychological evaluation. Reasons DLB may be misdiagnosed include:

Some “core” clinical features of DLB may not appear or may overlap with AD.
Presence and severity of concurrent AD pathology in DLB may modify the clinical presentation, with decreased rates of hallucinations and parkinsonism and increased neurofibrillary tangles.
Failure to reliably identify fluctuations—variations in cognition and arousal, such as periods of unresponsiveness while awake (“zoning out”), excessive daytime somnolence, and disorganized speech.²⁷

Detecting and characterizing cognitive deficits in dementia patients using neuropsychological testing is important in establishing a clinical diagnosis, determining baseline levels of impairment, forming a prognosis, and initiating disease-specific treatments. Differences in neuropsychological findings in AD and DLB are outlined in Table 2.^16,28-33 Several studies have suggested using these measures to differentiate patients with DLB from those with AD.²⁰

Table 2

Diagnostic testing for Alzheimer’s disease and dementia with Lewy bodies

Alzheimer’s disease	Dementia with Lewy bodies
Neuropsychological testing findings
Relatively more impairment on verbal memory tasks, delayed recall, delayed recognition, and encoding and storing information.²⁸ Dysfunction of episodic memory function	Relatively more impairment on attention or concentration, verbal fluency, visuoperceptual, visuoconstructive, visual memory tests, and frontal executive functions.²⁸ Relatively preserved confrontation naming and verbal memory
MRI findings
Diffuse cortical atrophy, relatively greater volume loss in hippocampus and medial temporal lobe structures (strong correlation with severity)²⁹	Mild generalized cerebral cortical atrophy with minimal hippocampal atrophy and relative preservation of medial temporal lobe structures³⁰
[18F]FDG PET
Widespread metabolic deficits in neocortical association areas, with sparing of the basal ganglia, thalamus, cerebellum, primary sensory motor cortex, and visual cortex	Widespread cortical hypometabolism, more marked in primary visual and occipital association areas, and less severe in parietal, frontal, and anterior cingulate cortices.³¹ Severe cholinergic deafferentation of the neocortex, particularly in posterior cortical regions³²
Single photon emission computed tomography
Parietotemporal hypoperfusion	Occipital hypoperfusion
123I-FP-CIT SPECT (DaT scan)
No significant loss of DaT	Low nigrostriatal terminal density of DaT caused by severe nigrostriatal degeneration¹⁶
Myocardial scintigraphy with MIBG
No significant change in MIBG uptake	Decreased MIBG uptake³³
123I-FP-CIT: 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane; DaT: dopamine transporter; FDG PET: [18F]-fluoro-d-glucose positron emission tomography; MIBG: metaiodobenzylguanidine; SPECT: single photon emission computed tomography