Dementia With Lewy Bodies Markedly Higher in Men

Pauline Anderson

September 20, 2013

A unique new population-based study that focused on Olmsted County, Minnesota, shows that the overall incidence of dementia with Lewy bodies (DLB), considered the second leading cause of neurodegenerative dementia after Alzheimer's disease, is lower than that of Parkinson's disease (PD), increases steeply with age, and is markedly higher in men than in women.

It's important to determine the incidence of DLB and PD dementia (PDD) and to differentiate between the 2 conditions because this could affect treatment approaches, said lead author, Rodolfo Savica, MD, Department of Neurology, Mayo Clinic, Rochester, Minnesota, currently at the Department of Neurology, University of Utah, Salt Lake City.

"Patients with dementia with Lewy bodies may have more symptoms, such as hallucinations, cognitive fluctuations, and myoclonus, which can be bothersome, so knowing what's going on is very important, firstly to treat the symptoms properly and secondly to help find a cure," he told Medscape Medical News.

The "1-year rule" is used to differentiate between DLB, which refers to cases where dementia develops before or within a year after parkinsonism onset, and PDD, a term used when dementia appears more than a year after PD. In this study, the incidence of DLB was also higher than that of PDD, which the researchers did not anticipate.

Although the distinction between these 2 conditions is somewhat arbitrary and even experts have trouble differentiating between them, separating them is currently necessary for clinical research and future targeted therapies, said Dr. Savica.

The study was published online September 16 in JAMA Neurology.

Rochester Epidemiology Project

For this analysis, researchers studied the population of Olmsted County, Minnesota, over a period of 15 years (January 1991 to December 2005). During that period the population grew from 110,780 to 138,098.

The study used a medical records linkage system of the Rochester Epidemiology Project that includes all medical providers in Olmsted County.

All residents of the county who met criteria for DLB or PDD with symptom onset during the study period were included as incident cases. Researchers identified 542 incident cases of parkinsonism, of which 64 were DLB and 46 were PDD.

The researchers found that the overall incidence of PDD was 2.5 cases per 100,000 person-years, lower than the incidence of DLB at 3.5 cases per 100,000 person-years.

DLB and PDD incidence rates uncovered by the study should be considered minimal estimates because some patients with Lewy body pathology in whom parkinsonism or mild dementia remained minimal may have been missed, the researchers say.

At 14.2 cases per 100,000 person-years, the incidence of PD was 4-fold higher than that of DLB. And that rate was 2.4 times higher than the incidence of DLB and PDD combined (14.2 vs 5.9).

That the incidence rate of DLB is lower than that of PD didn't surprise Dr. Savica, but he was a little taken aback that the incidence of DLB is higher than the PDD incidence. "We were expecting the opposite," he said.

The incidence of PDD was similar in men and women (2.3 vs 2.7), but this was not the case with DLB. The study uncovered a "striking" sex difference in DLB rates. During the peak incidence decade (ages 70 to 79 years), the rates were 77.8 for men compared with 19.5 for women, which represents a 4-fold difference. In the same age range, the men-to-women difference in the PD incidence rate was 181.6 vs 69.4.

"We are saying that men are more affected than women," said Dr. Savica. "Age is the most important driver, but sex is also important. We have to consider that men and women are different biologically and men and women may have different kinds of diseases. It means that in future, we may need different therapeutic approaches, or strategies, to treat men and women."

There are several possible explanations for this sex gap in DBL, said Dr. Savica. In addition to men having a different genetic makeup, men may have had more exposure to environmental factors (such as chemicals in farming). As well, hormones and cultural and social factors may contribute to the sex differences in incident rates.

For the most part, the researchers were able to predict DLB pathology from clinical findings. Among the 542 patients with parkinsonism, 65 had died during the study period and had undergone brain autopsy. Among these patients, 31 were classified as having DLB or PDD.

In 94% of cases, the clinical diagnoses of DLB was neuropathologically confirmed, a rate Dr. Savica said is "extremely high." In contrast, the equivalent rate for PDD was only 57.1%.

Patients with DLB were younger than those with PDD at onset of symptoms (76.3 years vs 81.4 years). In addition, the clinical characteristics of the 64 cases of DLB differed from those of the 46 PDD cases; for example, patients with DLB had more hallucinations (62.5% vs 20.0%; P < .001), more cognitive fluctuations (25% vs 8.9%; P = .03), and, although not statistically significant, more myoclonus (12.5% vs 4.4%; P = .15).

"These clinical features may be extremely important to differentiate between these 2 diseases," said Dr. Savica. "It's very important too because it can guide the clinician to make a better diagnosis."

The study is the first of its kind ever done in North America. "It includes the entire population of Olmsted County, not just a piece of the population," said Dr. Savica. "It's unique because it's based on a large population-based sample using the unique records linkage system of the Rochester Epidemiology Project."

Olmsted County is primarily a community of white residents of European descent, so the findings may not be generalizable to populations with different ethnic, social, and economic characteristics. However, Dr. Savica pointed out that the county is similar in many respects to the rest of US population.

The current study serves as a starting point for further population-based research. Dr. Savica and his colleagues already have other studies of DLB and PDD in various stages of completion that should contribute to the understanding of these neurodegenerative conditions and further clarify clinical findings, cause of death, and response to treatment.

The study was supported by the National Institute on Aging of the National Institutes of Health and by the Mayo Foundation for Medical Education and Research. The authors have disclosed no relevant financial relationships.

JAMA Neurol. Published online September 16, 2013. Abstract

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