Dementia with Lewy bodies (DLB) is one of the most common types of degenerative dementia, affecting an estimated 1.4 million people in the United States.1 It is also the most misdiagnosed form of dementia, taking on average more than 18 months and 3 physicians to reach a correct diagnosis.
Characterized by an abnormal build up of alpha-synuclein proteins in the brain, DLB diagnosis is primarily clinical, with a definitive diagnosis only achieved through postmortem autopsy. Its similarities with Alzheimer’s and Parkinson’s disease, and the general lack of awareness and familiarity with DLB among the medical community, further complicate diagnosis.
“There is much less awareness of DLB compared to Alzheimer’s disease at all levels – amongst the general public, amongst general practitioners, and even amongst specialists in hospitals,” Professor John O’Brien, MD, chair of Old Age Psychiatry at the University of Cambridge, told Neurology Advisor. According to a 2010 report based on a survey of caregivers of people with DLB, 78% of cases were initially misdiagnosed: 54% as Alzheimer’s or another type of dementia or mild cognitive impairment; 39% as Parkinson’s disease or another movement disorder; and 24% as a psychiatric disorder.2
“People with DLB commonly have some particular symptoms, such as visual hallucinations, marked fluctuations or variations in their memory and thinking, and slowed movements or tremor like what is seen in those with Parkinson’s,” Dr O’Brien said. However, not all patients with DLB will have all of the symptoms, especially during the early stages of the disease, and those with other dementias may have some of the same symptoms, making recognition and early diagnosis a challenge.
There are, however, certain features that more commonly occur in DLB than in “pure” Alzheimer’s disease, including “mild spontaneous motor features of Parkinsonism – such as bradykinesia, rigidity, masked faces but without a resting tremor, recurrent and well-formed visual hallucinations, and fluctuating cognition with pronounced variations in attention or alertness,” David P. Salmon, PhD, a professor of neurosciences at the University of California, San Diego, and a key investigator at the Shirley-Marcos Alzheimer’s Disease Research Center, told Neurology Advisor. “These clinical distinctions form the basis for consensus criteria adopted by the International Consortium on DLB to clinically diagnose DLB and distinguish it from Alzheimer’s.”3 Autonomic dysfunction, falls, and REM sleep behavior disorder are some of the supportive features that are more prevalent among DLB patients than Alzheimer’s patients, he said.
The main differences in pathology between DLB and Alzheimer’s are the “presence of Lewy bodies in DLB in the brain stem and basal brain, and amyloid tangles in Alzheimer’s in temporal cortices,” Luis Peraza, PhD, a research associate with the Institute of Neuroscience at Newcastle University in the UK, told Neurology Advisor. “In DLB, Lewy bodies appear within the neurons and mainly start in the brain stem affecting the autonomic nervous system, then migrating to the basal brain where the disease affects dopaminergic neurons, altering cognition and movement control.” In contrast, Alzheimer’s pathology starts within the temporal cortices, which govern memory storage. Amyloid pathology often also occurs in DLB,4 which is likely responsible for the overlapping cognitive symptoms seen in DLB and Alzheimer’s disease.
Accurate diagnosis is especially important, as DLB is typically more debilitating than Alzheimer’s or Parkinson’s, Dr Peraza told Neurology Advisor. Misdiagnosis may also lead to inappropriate treatment plans, which in patients with DLB can be especially detrimental. For example, typical antipsychotics prescribed to Alzheimer’s patients may in fact worsen psychiatric symptoms in patients with DLB.
Acetylcholinesterase inhibitors such as rivastigmine, donepezil, and galantamine are considered first-line treatment in DLB patients for psychiatric symptoms including apathy, anxiety, hallucinations, and delusions, although in a minority of patients, these drugs may worsen motor symptoms.5 Standard neuroleptics should be avoided due to sensitivity; however atypical neuroleptics including clozapine, quetiapine, or aripiprazole can be used when cholinesterase inhibitors are ineffective. Motor symptoms may be improved with levodopa/carbidopa, however treatment may exacerbate psychiatric symptoms in some DLB patients. Other approved drugs include selective serotonin reuptake inhibitors for the treatment of depression, and memantine for cognitive and neuropsychiatric symptoms.6