PET/MRI Scans May Distinguish LATE Dementia from Alzheimer’s Disease
A new imaging approach combining positron emission tomography (PET) and magnetic resonance imaging (MRI) may offer a way to distinguish a recently identified form of dementia, Limbic-predominant age-related TDP-43 encephalopathy (LATE), from Alzheimer’s disease (AD). The findings, from a retrospective observational study, could be a significant step forward in diagnosing and understanding this increasingly prevalent neurodegenerative disorder.
Understanding LATE
LATE is caused by abnormal deposits of the protein TDP-43 in specific areas of the brain. It’s becoming increasingly recognized as a common cause of dementia, particularly in older adults. The challenge lies in its clinical similarity to Alzheimer’s disease – both often present with memory problems – making accurate diagnosis difficult. Crucially, because the underlying causes differ, effective treatments for AD may not be effective for LATE, and vice versa.
Currently, a definitive diagnosis of LATE can only be made after death, through examination of brain tissue. This lack of a reliable in vivo diagnostic tool has hindered research into the risk factors, progression, and potential treatments for LATE.
The Power of Combined Imaging
Researchers analyzed nearly 1,000 PET scans obtained from cognitive disorder clinics. They developed specialized PET templates designed to highlight patterns of brain changes characteristic of both LATE and AD, utilizing data from the Alzheimer’s Disease Neuroimaging Initiative and the University of Utah datasets. These templates were then used to categorize participants as likely having pure LATE, LATE with AD, or pure AD, based on their PET scan results. MRI data was then compared across these groups.
The analysis categorized 13% of the PET scans as probable LATE (with 10.6% of those also showing signs of AD), and 23.7% as probable AD without LATE. This distribution underscores the growing recognition of LATE as a significant contributor to dementia.
MRI Reveals Distinct Patterns
Detailed analysis of MRI scans revealed distinct patterns of brain volume loss in the different groups. In individuals with pure LATE, the most significant shrinkage was observed in the medial temporal lobe – a region of the brain critical for memory.
However, in cases where LATE co-existed with AD, the pattern of volume loss shifted. The orbitofrontal gyrus (involved in decision-making and social behavior) and the lateral temporal lobe showed the greatest vulnerability. This suggests that the presence of AD alters the way LATE affects the brain.
Specifically, the entorhinal cortex and amygdala emerged as key regions for differentiating mixed LATE and AD cases from pure LATE and pure AD cases. Importantly, the researchers found that the same hemisphere of the brain was typically affected in both LATE and AD cases.
Implications for Diagnosis and Treatment
The study highlights the potential of combining PET and MRI data to improve the accuracy of dementia diagnosis. While not a definitive diagnostic test, this imaging approach could help clinicians identify individuals who may be experiencing LATE pathology, even while they are still alive. Here’s a crucial step towards developing targeted therapies for this condition.
The researchers emphasize that the lack of diagnostic tools has been a major obstacle to progress in LATE research. Being able to identify LATE in vivo would facilitate studies aimed at understanding the risk factors, clinical features, and optimal management strategies for this increasingly common form of dementia.
The study, published in Nuclear Medicine, builds on growing understanding of LATE, first formally described in by a consensus working group. The National Institute on Aging provides resources for understanding LATE, recognizing its increasing importance in the landscape of age-related cognitive decline.
Further research is needed to validate these findings in larger and more diverse populations. However, this study offers a promising avenue for improving the diagnosis and treatment of LATE, ultimately benefiting individuals and families affected by this challenging condition.
Reference
Ngam PI et al. Copathologies of limbic-predominant age-related TDP-43 encephalopathy and Alzheimer disease: [18F]FDG PET statistical mapping and quantitative MRI volumetry. Nucl Med. ;DOI:10.2967/jnumed.125.270614.