Preserved Hippocampal Volume a Marker for DLB?

Fran Lowry

November 10, 2016

Preserved hippocampal volumes appear to be a sign of increased risk of developing dementia with Lewy bodies (DLB) in people with mild cognitive impairment (MCI), new research suggests.

"Shrinkage in the hippocampus is an early sign of Alzheimer's disease, but we have found that this region of the brain is preserved in people who develop dementia with Lewy bodies," lead author, Kejal Kantarci, MD, from Mayo Clinic, Rochester, Minnesota, and a member of the American Academy of Neurology, told Medscape Medical News.

The discovery could help distinguish people at risk for DLB from those at risk for Alzheimer's disease in the early stages, before they develop dementia, Dr Kantarci said.

Their findings were published online November 2 in Neurology.

"Dementia with Lewy bodies frequently coexists with Alzheimer's disease and these individuals may have some Alzheimer's disease-related pathologies in their brain as well, but it is as important to distinguish those who would develop dementia with Lewy bodies versus Alzheimer's disease," she said. "Being able to identify people who are at risk for dementia with Lewy bodies is important so they can receive the correct treatments early on.

"Early diagnosis also helps doctors know what drugs to avoid as up to 50% of people with dementia with Lewy bodies have severe reactions to antipsychotic drugs," Dr Kantarci said.

The current study included 160 patients with MCI from the Mayo Clinic Alzheimer's Disease Research Center who participated in an MRI study during October 2005 to January 2014 and were followed approximately annually with clinical evaluations and neuropsychological testing.

Hippocampal volumes were analyzed from 3T MRIs, and hippocampal atrophy was determined from the most normal 10th percentile of the measurement distributions in a separate cohort of clinically diagnosed patients with Alzheimer's disease dementia.

During a median follow-up of 2.0 years (range, 0.7 - 8.1 years), 20 (13%) patients with MCI progressed to probable DLB and 61 (38%) progressed to Alzheimer's disease dementia.

"It is called 'probable' because the disease can only be definitively diagnosed by autopsy after death," Dr Kantarci explained.

Patients with MCI with preserved hippocampal volume were 5.8 times more likely to develop probable DLB than those who had hippocampal atrophy (estimated subdistribution hazard ratio [HR], 5.8; 95% confidence interval [CI], 1.86 - 18.0; P = .002).

They also had a lower risk for progression to Alzheimer's disease than patients with hippocampal atrophy (estimated subdistribution HR, 0.56; 95% CI, 0.34 - 0.91; P = .02).

Seventeen of the 20 patients (85%) who developed DLB had a normal hippocampal volume, and 37 of the 61 patients (61%) who developed Alzheimer's disease had hippocampal atrophy.

"Patients who have dementia with Lewy bodies have problems with attention, visual processing or interpreting visual information, and problem solving early on, before they develop dementia, whereas Alzheimer's disease is characterized by memory impairment, so there are some differences in clinical presentation," Dr Kantarci said.

"Now, in this study, we are finding that if we use this imaging marker of hippocampal volume along with some of these cognitive difficulties that are more aligned with dementia with Lewy bodies, we may be able to separate them from Alzheimer's disease patients early, before they develop dementia," she said.

Being able to differentiate patients who have dementia with Lewy bodies from those with Alzheimer's disease is important for many reasons, Dr Kantarci said.

"We know that dementia with Lewy body patients are very sensitive to traditional antipsychotic medications and it could be important to pick them out at this very early stage when they do not have the diagnosis of dementia with Lewy bodies yet. There are also lots of clinical trials underway in Alzheimer's disease and dementia with Lewy bodies so hippocampal volume might be very useful in the future to identify the right people for these trials and not enroll them into trials where they may not benefit from anything," she said.

Richard B. Lipton, MD, Edwin S. Lowe Professor and vice chair of neurology, Albert Einstein College of Medicine, Bronx, New York, agrees.

"As we develop treatments designed to prevent the progression of MCI to dementia, identifying persons at risk for particular types of dementia will help target patients likely to respond to particular types of therapy," Dr Lipton told Medscape Medical News.

"The study by Kantarci and coworkers is a large step towards developing studies of persons with MCI likely to develop either Alzheimer's disease dementia or diffuse Lewy body dementia," he said.

"Their findings suggest that in studies designed to prevent AD dementia, persons with amnestic MCI and reduced hippocampal volumes might be good candidates," Dr Lipton said. "In studies designed to prevent the onset of DLB dementia, persons with nonamnestic MCI and preserved hippocampal volumes might be good candidates.

This current study relied on clinical diagnosis, he noted. "As [Alzheimer's disease] AD and DLB pathology often co-occur, the use of amyloid PET [positron emission tomography] or postmortem studies may usefully improve the assessment of patients with more than one diagnosis," he concluded. "The influence of vascular factors should also be considered."

The study was funded by the National Institutes of Health. Dr. Kantarci has disclosed no relevant financial relationships. Dr Lipton reports that he conducts research in neuroimaging in cognitive aging and dementia sponsored by the National Institutes of Health and has received funding from Lilly and Merck in the dementia area.

Neurology. Published online November 2, 2016. Abstract

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