A quantitative imaging approach using FDG PET and MR may help clinicians distinguish a recently recognized form of dementia known as limbic-predominant age-related TDP-43 encephalopathy, or LATE, from Alzheimer’s disease, according to research published online in the Journal of Nuclear Medicine.

LATE is a neurodegenerative condition seen in older adults that presents with memory loss similar to Alzheimer’s disease. Unlike Alzheimer’s, which is associated with amyloid and tau protein accumulation, LATE is defined by TDP-43 protein deposits in the limbic system. At present, definitive diagnosis requires postmortem neuropathologic examination, and no clinically approved biomarker exists.

“The distinction in the causes of these types of dementia is critical, especially in the era of anti-amyloid therapies,” said Satoshi Minoshima, M.D., Ph.D., FSNMMI, professor of radiology and imaging sciences at the University of Utah in Salt Lake City. “Because LATE has a different underlying pathology and a seemingly different prognosis, it cannot be diagnosed or treated in the same way as Alzheimer’s disease.”
Researchers developed stereotactic surface projection PET templates derived from autopsy-confirmed cases of LATE and Alzheimer’s disease. From these, they generated z score maps and applied z score product indices to 944 consecutive 18F-FDG PET scans referred from cognitive disorder clinics at a tertiary care center. Patients were categorized as probable LATE, probable mixed LATE and Alzheimer’s disease, or probable Alzheimer’s disease without LATE. Quantitative MR volumetry and clinical data were compared across groups.

Among the cases analyzed, 13% were classified as probable LATE, including 2.4% with pure LATE and 10.6% with mixed pathology. Another 23.7% were categorized as probable Alzheimer’s disease without LATE. MR findings showed predominant medial temporal lobe involvement in pure LATE, while mixed cases more often involved the orbitofrontal gyrus and lateral temporal lobe. The study also found that LATE and Alzheimer’s-related changes tended to affect the same hemisphere within individuals.

“Our study aimed to introduce a quantitative diagnostic framework using commonly available imaging tests to identify LATE,” Minoshima said, adding that the approach may support clinical management and further investigation of the condition.

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