A 72-year-old woman with no neurological or psychiatric history presented with gradually worsening memory loss over 2–3 years. She had difficulty recalling names, sometimes forgot recent events, repeated herself, and was occasionally irritable. Despite these symptoms, she remained independent in daily activities and scored 27/30 on the Mini-Mental State Examination (MMSE). Laboratory tests, including thyroid function, vitamin B12, and folic acid, were normal. Over nine years of follow-up, her cognitive decline was slow and stable (MMSE 23/30 at year nine), and she continued to manage her daily activities independently. Initial MRI was normal, but after four years, imaging showed early enlargement of the insula and right frontal lobe. FDG-PET scan revealed moderate hypometabolism in the left anterior and medial temporal cortex, while amyloid-PET was negative for β-amyloid plaques, ruling out Alzheimer’s disease. Subsequent FDG-PET imaging over the years showed persistent but stable hypometabolism in the left temporal pole and mild insular cortex enlargement, with no significant structural brain changes. Language impairment developed, partly related to fluctuating depressive symptoms, but her autonomy in daily living was preserved. The diagnosis was limbic-predominant age-related TDP-43 encephalopathy (LATE), a neurodegenerative disorder affecting the limbic system in older adults. LATE is characterized by slow progression, semantic memory impairment, and preserved neocortical functions. This case highlights the need for improved diagnostic criteria and biomarkers to distinguish LATE from Alzheimer’s disease and optimize management strategies.