A possible case of Limbic-predominant age-related TDP-43 encephalopathy (LATE) in a Black Female with caregiver burden and limited resources: A Novel Diagnosis with presentation similar to Alzheimer's

Abstract

<h3>Introduction</h3> Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a proposed neurodegenerative disorder of older adults (typically >80 years old)⁽¹⁾. It presents primarily as an amnestic dementia and is thought to be due to a TDP-43 proteinopathy in limbic system structures, including the hippocampus. There could be coexisting hippocampal sclerosis pathology in some patients presenting with LATE. In community-based autopsy cohorts, ∼25% of brains had a sufficient burden of LATE-neuropathology changes (LATE- NC) to be associated with discernible cognitive impairment. (ADNC) ⁽³⁾. In a retrospective study described by Kapasi et Al, there exist a class I evidence that LATE-NC and Alzheimer's disease pathologic changes are associated with different trajectories of late-life cognitive decline. Persons with pure LATE-NC follow a slower trajectory compared to those with pure ADNC. LATE-neuropathology changes may be co-morbid with Alzheimer's disease neuropathological changes. Those with mixed LATE/ADNC have a steeper decline than individuals with either pathology alone ⁽⁴⁾. The following is a unique case presentation of a patient with possible LATE or a combination of LATE/AD NC as demonstrated by rapid amnestic dementia and changes in brain MRI. In addition, this case shows how the treatment is tailored based on family preference and available resources <h3>Methods</h3> A single patient case of interest was chosen and verbal consent was obtained from the patient. Our initial review was conducted with a literature search at Pubmed. 57 articles were retrieved which was narrowed down to 10 articles after irrelevant topics were excluded. The clinical presentation of the case was found to be correlated with the relevant reports in the research literature implying a possible rationale for LATE vs ADNC for the patient. <h3>Results</h3> Case presentation: This is a case of a 91-year-old female with no past psychiatric history, a medical history significant of HTN, and stable angina who presented to the memory clinic with a decline in short-term memory in the past 18 months that has progressively worsened over the past 6 -8 months. The patient would forget conversations and has been misplacing items at home. The patient would engage in dangerous behaviors to include forgetting the stove on. Also associated were neuropsychiatric symptoms of agitation, irritability, and insomnia. The patient became easily irritable and would attempt to hit others. These behaviors were all new to this patient and her family was very concerned. Taking care of her became increasingly challenging and they decided to consult professional help. The patient became increasingly dependent on all ADLs except feeding and toileting. She had been unable to perform all IADLS for the past two years. On MMSE, she scored 24/30 with most points lost in immediate recall. Further neuropsychiatric testing revealed deficiency in verbal fluency, clock drawing, delay recall, and word list learning. The MRI of the brain indicated a decrease in Hippocampal volume at 7 percentiles for her age as per NEUROQUANT evaluation; almost 2 standard deviations below the mean. Mild/moderate chronic white matter microvascular ischemic changes were also seen. No acute ischemia was noted. The caregiver burden was extremely high and memory medication was not a priority for the family. The family did not qualify for Medicaid and declined much-needed social services that could provide respite and promote social engagement. Paying out of pocket was a hindering factor. A low-dose second-generation antipsychotic was initiated with good remission of agitative symptoms. <h3>Conclusions</h3> The patient's advanced age, delayed onset of the cognitive impairment, precipitous memory decline, and the findings on brain MRI are suggestive of a possible diagnosis of LATE versus LATE ADNC. However, this diagnosis or other forms of dementia cannot be ruled out without a brain biopsy. This case indicates that further research on diagnosing and targeting patients with TDP-43 might greatly improve the disease burden. Furthermore, the differences in social-economic status can greatly add to disparities in dementia care. <h3>This research was funded by</h3> None