ARTICLE IN BRIEF
LEWY BODY DEMENTIA: Lewy bodies appear as dense intracellular inclusions here.
Investigators reported that myocardial scintigraphy was a better predictor than brain SPECT scanning in identifying which patients would convert to a probable Lewy body dementia.
A cardiac imaging test, myocardial scintigraphy, can be a good tool for predicting whether someone will convert from a diagnosis of possible to probable dementia with Lewy bodies (DLB), though the test is not used for that purpose in the United States, a new paper in the Oct. 11 online edition of Neurology suggests.
Investigators reported that using myocardial scintigraphy to detect sympathetic nerve damage associated with DLB was a better predictor than brain perfusion single photon emission computer tomography (SPECT) in predicting whether a patient would convert from possible DLB to probable DLB.
Myocardial scintigraphy — which is performed using a radiotracer that traverses the myocardial capillary system and enters myocardial cells, measuring regional myocardial blood flow and cell viability — is used in Japan for diagnosing DLB and to a lesser extent in Europe, but the test has not been adopted in the US for a variety of reasons.
“In the earliest clinical stages of DLB, diagnosis can be difficult because the core features of DLB may be too mild for physicians to detect,” said lead researcher Haruhiko Oda, MD, PhD, in an e-mail to Neurology Today.
DLB may be confused with Alzheimer's disease (AD) or Parkinson's disease (PD) or schizophrenia, especially if the patients seem to have cognitive symptoms and visual hallucinations, he said. The study noted that “if the typical DLB features of fluctuating cognition, visual hallucination and parkinsonism are clearly present, it is simple to differentiate DLB from AD, but not all patients manifest these features early in the course of DLB.”
“I-MIBG myocardial scintigraphy at the initial presentation of DLB appears to be clinically useful,” the authors concluded.
STUDY METHODOLOGY
The investigators tracked 94 individuals with a diagnosis of possible DLB, based on standard criteria, for a year to determine who would convert to a probable diagnosis. The patients each underwent myocardial scintigraphy using the radioactive tracer I-123 metaiodobenzyl guanidine (I-MIBG) and a N-Isopropyl-p-1231-iodoamphetamine (123I-IMP) brain perfusion SPECT scan. At the one-year mark, the researchers reassessed the patients clinically to determine which patients had gone on to meet the criteria for probable DLB: they looked for evidence of progressive disabling mental impairment with at least one of three core features — fluctuating cognition, visual hallucinations and parkinsonism — for the diagnosis of possible DLB and two out of three for a diagnosis of probable DLB.
“The positive predictive value (PPV) of brain perfusion SPECT in the subjects was 0.45. The PPV of I-MIBG myocardial scintigraphy in the subjects was 0.88,” Dr. Oda, said. The study was conducted at the Hyogo Brain and Heart Center in Himeji, Hyogo, in Japan.
The new paper found that the cardiac imaging test was a better predictor than brain SPECT scanning in identifying which patients would convert to a probable DLB diagnosis: The test had a specificity of 88 percent, a sensitivity of 94 percent, and a positive predictive value of 88 percent for the best I-MIBG threshold.
EXPERTS COMMENT
An editorial that accompanied the new study characterized it as an “exciting paper” that “clearly highlights the test's potential clinical utility. But the editorial authors — Clive Ballard, MD, of King's College, London, and Timo Grimmer, MD, of the Technical University of Munich — said that more research was needed to validate the findings.
They noted that although “visual hallucinations occurred more in the ‘converter’ group, this was not different statistically and is therefore of uncertain value...Further, it would be worth investigating whether the predictive value could be improved by adding a requirement for persistence of visual hallucinations or by focusing on individuals with visual hallucinations in the absence of cataracts, other eye pathology, or substantial impairment of visual acuity, which are strongly related to visual hallucinations in people with Alzheimer disease.”
They continued: “It was also interesting that fluctuation was more common in ‘nonconverters,’ which probably supports previous literature in suggesting that fluctuation is often misdiagnosed and highlights the importance of using a validated assessment tool or a validated attentional assessment for cognitive fluctuation.”
Experts interviewed by Neurology Today said that while the results looked promising, they doubted the test would take off in the US for DLB diagnosis, in part because insurance companies do not normally pay for indications related to dementia. Also, the meaning of test results is not always clear when it comes to DLB.
DR. BRADLEY F. BOEVE: “Findings are difficult to interpret in patients who are diabetic and/or those who are using any of dozens medications that interfere with the radioligand” that is used for the imaging test.
DR. DAVID S. GOLDSTEIN said that the lack of both US-based clinical trials and insurance reimbursement factors into why myocardial scintigraphy has not made inroads in the diagnosis of dementia with Lewy bodies in the US.
DR. JAMES GALVIN said that typically a diagnosis of Lewy body dementia is made clinically, not with imaging tests.
“Findings are difficult to interpret in patients who are diabetic and/or those who are using any of dozens medications that interfere with the radioligand” that is used for the imaging test, Bradley F. Boeve, MD, professor of neurology at the Mayo Clinic in Rochester, MN, who was not involved with the study, told Neurology Today.
Dr. Boeve said making a timely diagnosis is important because patients can be started on an appropriate treatment, particularly an acetylcholinesterase inhibitor, which helps improve symptoms in many patients.
Having an accurate diagnosis is also important for patients and caregivers who want to understand what the course of disease is likely to entail. Patients and their families need to be able to “plan for the future with the knowledge that a complex neurodegenerative disorder is present,” Dr. Boeve said.
David S. Goldstein, MD, PhD, chief of the Clinical Neurocardiology Section at the NIH's National Institute on Neurological Disorders and Stroke, said that the lack of both US-based clinical trials and insurance reimbursement factors into why myocardial scintigraphy has not made inroads in the diagnosis of DLB in the US.
While DLB is typically thought of as a brain disease, it is a systemic disease that affects multiple systems in the body. Dr. Goldstein said research has found an association between a loss of sympathetic nerves in the heart and Parkinson's disease, pure autonomic failure, and DLB. In the case of PD, the sympathetic nerve damage may occur before movement problems become apparent.
Dr. Goldstein is studying the mechanisms by which the Lewy bodies protein, alpha-synuclein, cause damage to brain cells. In a paper published in the Journal of Neuroimaging in 2012, Dr. Goldstein wrote that “imaging of sympathetic innervation of the heart may provide a sensitive, specific means to diagnose DLB differentially from other forms of dementia, by detecting catecholaminergic denervation associated with the intraneuronal deposition of alpha-synuclein.”
James Galvin, MD, MPH, professor of neurology and psychiatry at New York University Langone School of Medicine, noted the difficulties in diagnosing LBD. The symptoms such as constipation, inattentiveness and daytime drowsiness, rapid eye movement (REM) sleep behavior and depression may appear to be any number of other problems, he said, and it is not uncommon for patients to have seen various physicians for their symptoms before finally receiving a correct diagnosis. He said that typically a diagnosis of LBD is made clinically, not with imaging tests.
“To date, there are no specific patterns of MRI changes for DLB. MRIs are useful to rule out other conditions but not confirm DLB,” Dr. Galvin said.
DaTscan, a brain imaging test used to differentiate Parkinson's disease from essential tremor, is not approved for use in the US for DLB, he said. Brain perfusion SPECT scanning, which was used in the Japanese study for comparison to myocardial scintigraphy, may not provide sufficient information to rule in or rule out DLB, Dr. Galvin said.
