Alzheimer’s and Lewy bodies: When Two Pathologies Collide

DLB is one of two clinical diagnoses under the Lewy body dementia umbrella. When DLB co-occurs with Alzheimer’s disease, a clinical diagnosis is even more difficult to make as symptoms of both disorders may be present. Autopsy studies reveal that only 30% of people with DLB are diagnosed during life. The most frequent misdiagnosis is Alzheimer’s disease.

In a recent study of autopsy data in the National Alzheimer’s Coordinating Center (NACC) database, Lewy body pathology was the most common co-existing pathology in people with Alzheimer’s disease up to 80 years of age. Imaging tests can reveal Alzheimer’s disease in the brain, but no similar imaging tests can confirm the presence of Lewy bodies. While tests used in DLB diagnosis confirm the damage from the disease, no test shows the disease itself. One test used to aid in DLB diagnosis, MIBG scintigraphy, reveals a decline in cardiac nerves; this may be why people with Lewy body disorders have problems with blood pressure control.

While MIBG scintigraphy has been extensively studied in DLB in Japan, it hasn’t received the same amount of research or clinical interest in the U.S. People with diabetes and heart disease can have abnormal results with this scan, potentially limiting its use for diagnosis of DLB in the U.S.

Researchers at Banner Sun Health Research Institute analyzed data and samples from whole body autopsies of deceased participants of the Arizona Study of Aging and Neurodegenerative Disorders. Study subjects included people with autopsy-confirmed pure Alzheimer’s disease (AD), AD+DLB, Alzheimer’s disease with lesser amounts of Lewy bodies (ADLB), incidental (minimal) Lewy body disease (iLBD), Parkinson’s disease (PD), and people with no cognitive or movement disorders (healthy controls).

Tissue samples from the heart were studied to compare the number of cardiac nerve fibers. These fibers are very thin thread-like lines that transmit nerve signals. The subjects with PD and AD/DLB had fewer nerve fibers than the healthy controls. There was no significant difference in nerve fibers between healthy controls and subjects with AD, ADLB or ILBD.

In this study, nearly 50% of the AD+DLB cases had been diagnosed with AD during life. These mixed dementia cases are of considerable concern in clinical trials; individuals with AD+DLB can have a blended clinical picture and even different responses to medications than those with AD alone.

Further research is needed to determine the role MIBG scintigraphy might play in clinical trials for AD and DLB.

Reference: Geidy E Serrano, David Shprecher, Michael Callan, Brett Cutler, Michael Glass, Nan Zhang, Jessica Walker, Anthony Intorcia, Charles H Adler, Holly A Shill, Erika Driver-Dunckley, Shyamal H Mehta, Christine M Belden, Edward Zamrini, Lucia I Sue, Daisy Vargas, Thomas G Beach, Cardiac sympathetic denervation and synucleinopathy in Alzheimer’s disease with brain Lewy body disease, Brain Communications, Volume 2, Issue 1, 2020, fcaa004,