Individuals with NCDLB frequently experience repeated falls and syncope and transient episodes of unexplained loss of consciousness. Autonomic dysfunction, such as ortho- static hypotension and urinary incontinence, may be observed. Auditory and other nonvisual hallucinations are common, as are systematized delusions, delusional misiden- tification, and depression.
The few population—based prevalence estimates for NCDLB available range from 0.1% to 5% of the general elderly population, and from 1.7% to 30.5% of all dementia cases. In brain bank (autopsy) series, the pathological lesions known as Lewy bodies are present in 20%—35% of cases of dementia. The male-to-female ratio is approximately 1.521.
NCDLB is a gradually progressive disorder with insidious onset. However, there is often a prodromal history of confusional episodes (delirium) of acute onset, often precipitated by illness or surgery. The distinction between NCDLB, in which Lewy bodies are primar- ily cortical in location, and major or mild NCD due to Parkinson’s disease, in which the pa- thology is primarily in the basal ganglia, is the order in which the cognitive and motor symptoms emerge. In NCDLB, the cognitive decline is manifested early in the course of ill- ness, at least a year before the onset of motor symptoms (see the section ”Differential Di- agnosis” for this disorder). Disease course may be characterized by occasional plateaus but eventually progresses through severe dementia to death. Average duration of survival is 5—7 years in clinical series. Onset of symptoms is typically observed from the sixth through the ninth decades of life, with most cases having their onset when affected indi- viduals are in their mid-7OS.
Genetic and physiological. Familial aggregation may occur, and several risk genes have been identified, but in most cases of NCDLB, there is no family history.
The underlying neurodegenerative disease is primarily a synucleinopathy due to alpha- synuclein misfolding and aggregation. Cognitive testing beyond the use of a brief screen- ing instrument may be necessary to define deficits clearly. Assessment scales developed to measure ﬂuctuation can be useful. The associated condition REM sleep behavior disorder may be diagnosed through a formal sleep study or identified by questioning the patient or informant about relevant symptoms. Neuroleptic sensitivity (challenge) is not recom— mended as a diagnostic marker but raises suspicion of NCDLB if it occurs. A diagnosti- cally suggestive feature is low striatal dopamine transporter uptake on single photon emission computed tomography (SPECT) or positron emission tomography (PET) scan.
Other clinically useful markers potentially include relative preservation of medial tempo- uptake on SPECT/PET perfusion scan with reduced occipital activity; abnormal (low up- slow-wave activity on the electroencephalogram with temporal lobe transient waves.
Functional Consequences of Major or Miid
Individuals with NCDLB are more functionally impaired than would be expected for their cognitive deficits when contrasted to individuals with other neurodegenerative diseases, such as Alzheimer’s disease. This is largely a result of motor and autonomic impairments, which cause problems with toileting, transferring, and eating. Sleep disorders and prom- inent psychiatric symptoms may also add to functional difficulties. Consequently, the qual- ity of life of individuals with NCDLB is often significantly worse than that of individuals with Alzheimer’s disease.
Major or mild neurocognitive disorder due to Parkinson’s disease. A key differenti- ating feature in clinical diagnosis is the temporal sequence in which the parkinsonism and the NCD appear. For NCD due to Parkinson’s disease, the individual must develop cog- nitive decline in the context of established Parkinson’s disease; by convention, the decline should not reach the stage of major NCD until at least 1 year after Parkinson’s is diagnosed.