How common are Lewy body dementias? While dementia with Lewy bodies (DLB) is often cited as the second most common dementia after Alzheimer’s disease (AD), very few studies have measured its incidence. In the September 16 JAMA Neurology, researchers led by Walter Rocca at the Mayo Clinic in Rochester, Minnesota, reported some of the first data on the frequency of new cases of DLB and the closely related Parkinson’s disease dementia (PDD) in a U.S. population. Both disorders are characterized by the accumulation of the α-synuclein protein in Lewy bodies. In this study, the incidence for both conditions matched that for frontotemporal dementia, a rare disorder. The authors noted, however, that these numbers should be considered minimums, as the difficulty of recognizing these disorders meant some cases might have been missed.
Clinicians can have trouble diagnosing DLB because it shares characteristics with Alzheimer’s disease and PDD. Amyloid plaques are often present in the brains of patients with DLB, and people with the disorder typically move with difficulties akin to those experienced by Parkinson’s patients. To distinguish DLB from PDD, clinicians use the one-year rule: If dementia begins within one year of parkinsonism, they diagnose DLB; if later, PDD. DLB is marked by several distinctive clinical features, including visual hallucinations and fluctuations in alertness, attention, and cognitive function. DLB was first recognized about 20 years ago, and clinical criteria were formalized in 2005 (see McKeith et al., 2005). About 4 percent of dementia cases are currently classified as DLB (see Vann Jones et al., 2013).
To look at the incidence of DLB and PDD, first author Rodolfo Savica made use of data from the Rochester Epidemiology Project, which conglomerated all the medical records of the more than 110,000 residents of Olmsted County, Minnesota, into a single database. Savica and his colleagues first screened a 15-year period of these records for diagnostic codes related to parkinsonism. Then, using the full medical histories, Savica, a movement disorders specialist, re-diagnosed each patient’s disorder. Using this approach, the authors previously found an annual incidence of 14 new cases of Parkinson’s disease per 100,000 people in this population (ARF related news story).
The authors now report incidence rates of 3.5 cases of DLB and 2.5 cases of PDD per year per 100,000 people. These numbers are similar to the reported incidence of frontotemporal dementia (see Onyike and Diehl-Schmid, 2013). Lifetime incidence rose steeply with age, with about 32 new cases of DLB per 100,000 person-years in people older than 65. Across all ages, DLB incidence was, on average, about twice as high in men as in women, while PDD incidence was higher in men only in the oldest age group. By comparison, clinicians diagnose about 5,300 new cases of Alzheimer’s disease per year per 100,000 people between the ages of 65 and 74, with that number climbing dramatically at older ages (see Hebert et al., 2001). Olmsted County residents are largely of Northern European descent; it is unclear whether these results would generalize to other groups.
The Olmsted County DLB numbers are in sharp contrast with a previous 15-year incidence study in a French population, which found a rate of 112 new cases of DLB per year per 100,000 people over age 65 (see Perez et al., 2010). The authors noted that because they screened medical records for parkinsonism, they could have missed cases of DLB where movement problems had been undiagnosed. Biomarkers for DLB are in development (ARF related news story; ARF related news story) and may help provide more accurate diagnoses in future studies, Savica noted.
Commentators cautioned that these numbers are probably low. “It’s almost certain that DLB is more frequent than this,” Dennis Dickson at the Mayo Clinic in Jacksonville, Florida, told Alzforum. He speculated that screening medical records for dementia codes instead of parkinsonism might turn up many more cases of DLB, because dementia is much more common than parkinsonism. Dickson has worked with the authors but was not involved in the current study.
For PDD as well, the reported incidence should be regarded as a minimum number, because mild dementia in Parkinson’s patients may go undiagnosed, the authors noted. Some longitudinal studies have estimated that as many as 80 percent of Parkinson’s patients will eventually develop dementia (see Aarsland et al., 2003).
Curiously, in this study PDD diagnoses were much less accurate than DLB diagnoses. Of the 17 DLB patients who came to autopsy, 16 had been correctly diagnosed, for an accuracy rate of 94 percent. The one exception had amyloid plaques but no Lewy bodies. However, only eight of the 14 PDD patients, or 57 percent, proved to have been correctly diagnosed at autopsy. The other six brains did not contain Lewy bodies, and only half of them had Alzheimer’s pathology. Both the authors and commentators found this puzzling.
“How should we diagnosis patients who had parkinsonism and developed cognitive impairment, but had no Lewy body pathology? That needs further investigation,” Dickson told Alzforum.
Other commentators agreed that these diseases need to be better defined. “This is a wonderful study on this unique population with clinical and neuropathological data, but we still need to improve the classification of PDD and DLB clinically (better than the one-year rule) and, most importantly, neuropathologically (better than Lewy bodies and coexistence of AD pathology),” Brit Mollenhauer at Paracelsus-Elena Klinik, Kassel, Germany, wrote to Alzforum.
Savica pointed out that PDD in particular is poorly defined neuropathologically. Some recent studies suggest that dementia in PD is the result of Lewy body pathology spreading to brain areas affected in AD, others that it may be a result of concomitant AD pathology (ARF related news story; ARF related news story).—Madolyn Bowman Rogers
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