Novel Imaging Approach Identifies LATE Dementia
A novel quantitative approach combining FDG PET and volumetric MRI can objectively identify limbic-predominant age-related TDP-43 encephalopathy (LATE) — a recently recognized type of dementia frequently mistaken for Alzheimer’s disease. The study, published in the Journal of Nuclear Medicine and highlighted by SNMMI, represents a significant advance in the differential diagnosis of neurodegenerative dementias.
What Is LATE Dementia?
LATE (Limbic-predominant Age-related TDP-43 Encephalopathy) is a neurodegenerative form of dementia that predominantly affects the elderly and is characterized by abnormal accumulation of TDP-43 protein in the limbic regions of the brain, especially the hippocampus and amygdala. First formally described in 2019 by an international consensus group, LATE can cause clinical symptoms virtually indistinguishable from Alzheimer’s disease, including progressive memory loss and cognitive decline.
The major clinical challenge is that LATE frequently coexists with Alzheimer’s pathology, creating mixed presentations that further complicate diagnosis. Until now, definitive confirmation of LATE was only possible through post-mortem neuropathological examination, severely limiting the possibilities for targeted treatment during life.
Study Methodology and Results
Researchers retrospectively analyzed 944 18F-FDG PET cases referred from cognitive disorder clinics. Using three-dimensional stereotactic surface projection templates created from autopsy-confirmed cases, the team developed reference patterns to identify LATE in vivo.
The results are remarkable: of the 944 cases analyzed, 13% were characterized as probable LATE — with 2.4% pure LATE and 10.6% LATE coexisting with Alzheimer’s. Another 23.7% were classified as probable Alzheimer’s without LATE. Patients with LATE and LATE+Alzheimer’s showed a distinct pattern of decreased FDG metabolism in the medial temporal lobe, while Alzheimer’s and LATE+Alzheimer’s cases exhibited the classic pattern of hypometabolism in the posterior cingulate cortex, precuneus, and parietotemporal areas.
Subgroup analysis of the LATE+Alzheimer’s group revealed additive or synergistic effects of both pathologies, with three-quarters of cases exhibiting concordant lateralized metabolic brain changes, predominantly left-sided. This finding is particularly relevant for artificial intelligence applications in diagnostic imaging, as algorithms could be trained to recognize these specific patterns.
Implications for Clinical Practice
The ability to diagnose LATE in vivo opens new therapeutic possibilities. With the advent of anti-amyloid therapies for Alzheimer’s such as lecanemab and donanemab, precise differentiation between pure Alzheimer’s, pure LATE, and mixed forms becomes crucial — since treating a LATE patient with anti-amyloids would be ineffective and potentially harmful.
For nuclear medicine and radiology services, these findings reinforce the importance of standardized quantitative protocols for brain FDG PET. MRI volumetry, already available at many centers through software like NeuroQuant and Neuroreader, complements PET metabolic information, offering a more comprehensive multimodal assessment. Centers investing in advanced imaging protocols will be better prepared to incorporate these findings into clinical practice.
Future Outlook and Next Steps
While promising, these results need validation in larger prospective cohorts and more ethnically diverse populations. The true prevalence of LATE may be even higher than the 13% found in this study, considering that many dementia patients never undergo brain PET. The integration of plasma biomarkers for TDP-43, currently under development, with imaging assessment could create a more accessible and precise diagnostic workflow. The study marks an important step toward LATE transitioning from an exclusively post-mortem diagnostic entity to one that can be identified — and eventually treated — during the patient’s lifetime.
Source: AuntMinnie / SNMMI