2023-08-15 15:12:15
Why is this important?
Predominantly limbic age-related TDP-43 encephalopathy affects regarding a quarter of elderly people and is characterized by memory loss. Close to AD, and often misdiagnosed as such, LATE is a proteinopathy which is confirmed by pathology in the presence of aggregates of the TDP-43 protein in the internal temporal structures. LATE can also be observed concomitantly with other neurodegenerative or vascular diseases that can lead to dementia. With the advent of disease-modifying treatments (anti-amyloid), the need to distinguish LATE from Alzheimer’s disease or other dementias is becoming more pressing. A literature review reviewed this clinical entity, addressing in turn the symptoms, the influence of comorbidities, and the differential diagnosis with other types of dementia.
Clinical presentation of LATE
Cognitive decline appears slowly, with progressive loss of episodic memory. Despite the similarities with AD, differences in the presentation of the disease and its evolution make it possible to distinguish the two pathologies.
A progressive cognitive disorder that mainly affects memory and in a significant way throughout the disease should suggest LATE, whereas progressive memory loss, with the onset of disorders in other areas of cognition (language , executive or visuospatial functions) will be more in favor of an MA. The distinction therefore suggests a longitudinal follow-up of the patient. If episodic memory impairment is evident in LATE, working memory deficit is often present. Semantic memory can also be affected, especially when there is hippocampal sclerosis (there is progressive atrophy during the disease). A frontal syndrome may also be present, but this is also the case in AD and other dementias. Finally, the age of onset plays an essential role, an age greater than 80 years being rather in favor of a LATE.
Contribution of biomarkers to differential diagnosis
If no specific biomarker of LATE is yet available, structural imaging in MRI shows a predominant atrophy in the medial temporal lobe (MTL) in LATE, especially when it is severe and located in the anterior part. Atrophy is slower in isolated LATE than in AD, and accelerated in the presence of both pathologies. Amygdala atrophy is more specific for LATE, while reduced hippocampal volume is less so (also associated with AD). The hypometabolism observed in fluorodeoxyglucose positron emission tomography (PET-FDG) in the MTL and in the supraorbital frontal gyrus (versus inferior dentate gyrus) also makes it possible to distinguish MA and LATE with good sensitivity and specificity. In practice, in the presence of an isolated amnesic syndrome, atrophy of the amygdala and severe hippocampus, and in the absence of plasma biomarkers of AD (peptide beta-amyloid A 42/40 (A- ) and protein Tau-217 (T-)), we must think of a LATE. An A+/T- phenotype, associated with compatible MRI and PET-FDG profiles, should also lead to suspicion. On the other hand, it is more difficult to detect it in the presence of AD A+/T+.
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