Objective: To illustrate a case of parkinsonism in a patient with LATE syndrome.

Background: LATE syndrome is an emerging subclassification of TDP-43 proteinopathy. Symptoms include an amnestic dementia which is often mistaken for Alzheimer’s dementia (AD); some patients have co-morbid Alzheimer’s pathology while others do not^1,2. The decline in LATE is generally more gradual than in pure Alzheimer’s disease and there are subtle differences on neurocognitive testing. It is considered distinct from frontotemporal lobal degeneration both epidemiologically and pathologically, although there is overlap. Parkinsonism has not been described to our knowledge in LATE syndrome, and in fact has been reported as not associated with TDP-43 pathology in Alzheimer’s disease in one case series³.

Method: A 73 y.o. right-handed male presented with 1 year of left hand tremor. On non-motor review of systems, patient reported hyposmia but otherwise no autonomic abnormalities or symptoms of RBD. He reported cognitive dysfunction most notably short-term memory. His exam revealed decreased facial expression, mild left hand and general body bradykinesia, left hand rest and action tremor, and reduced bilateral arm swing on gait testing with normal stride length. No medications were started. He subsequently saw cognitive neurology who noted MOCA 24/30 with deficits in delayed recall. CT head with mild generalized atrophy. MRI not obtained due to pacemaker. Neuropsychological testing revealed deficits in naming, verbal fluency, and verbal and visual memory consistent with amnestic MCI. CSF analysis was not consistent with AD and a clinical diagnosis of LATE was made.

Results: The patient was followed in movement disorders clinic for 3 years (4 years since symptom onset) with no notable progression of his parkinsonism. He remains off medications.

Conclusion: Although a confirmation of a diagnosis of LATE syndrome will require pathology, this patient clinically fits the diagnosis with predominantly amnestic symptoms with CSF inconsistent with AD. Parkinsonism has not been reported in this relatively newly-described TDP-43 proteinopathy to our knowledge. This patient now has had 4 years of very mild, non-progressive parkinsonism which suggests either a slowly-progressive co-morbid idiopathic Parkinson’s disease or parkinsonism secondary to LATE.

References: 1. Robinson et al. Limbic-predominant age-related TDP-43 encephalopathy differs from frontotemporal lobar degeneration. Brain 2020 Sep 1;143(9):2844-2857. 2. Nelson et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain 2019: 142; 1503-1527. 3. Jung et al. TDP-43 in Alzheimer’s disease is not associated with clinical FTLD or parkinsonism. J Neurol. 2014 Jul;261(7):1344-8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsonism-in-a-patient-with-limbic-predominant-age-related-tdp-43-encephalopathy-late-syndrome/