The patient is a 75-year-old woman with a maternal history of Alzheimer’s disease. She has been followed by the Department of Psychiatric Neuropsychology for over fifteen years for a clinically isolated and highly stable amnesic syndrome. She has no significant vascular or psychiatric comorbidities and has maintained functional autonomy throughout the follow-up period. Her initial cognitive complaints emerged in her late 60s and prompted formal neuropsychological evaluation. At the age of 70, cognitive testing revealed an amnestic Mild Cognitive Impairment (MCI). General cognitive assessment included the Mini-Mental State Examination (MMSE 25/30), and a targeted evaluation of anterograde memory using the RL/RI-16, a French test comparable to the Free and Cued Selective Reminding Test (FCSRT). Her score on the RL/RI-16 was 36/48, consistent with isolated verbal episodic memory impairment. Despite these deficits, her autonomy in daily living activities was preserved. Structural MRI at that time revealed subtle atrophy of the right hippocampus. Cerebrospinal fluid (CSF) analysis showed hallmark abnormalities consistent with Alzheimer’s pathology, including elevated total tau (706 ng/L), phospho-tau (99 ng/L), reduced β-amyloid 1–42 (789 ng/L), and a low Aβ42/Aβ40 ratio (0.039).

Over a two-year period, the patient underwent several PET imaging studies using various fluorinated ligands to evaluate different aspects: cortical amyloid plaque accumulation (¹⁸F-florbetapir), neuronal activity (¹⁸F-FDG), tau protein density (¹⁸F-T807 or ¹⁸F-flortaucipir), and neuroinflammation (¹⁸F-DPA714) (2–5). At baseline, at age 71, scans revealed a moderate amyloid burden in the frontal cortex, without evidence of microglial activation or significant hypometabolism, suggesting preserved neuronal function and a lack of active neuroinflammation (Figures 1A–C). Cognitive assessment at that time showed a MMSE score of 25/30. Two years later, at age 73, the patient was re-evaluated using ¹⁸F-DPA-714, ¹⁸F-florbetapir, and, for the first time, ¹⁸F-flortaucipir. The amyloid load showed slight progression in the frontal cortex (Figure 1A’), consistent with the known amyloid trajectory, although amyloid distribution alone does not distinguish between typical and atypical forms of dementia. Microglial activity remained undetectable (Figure 1B’) reinforcing the absence of an active inflammatory process. Importantly, the new tau PET imaging revealed subtle binding in the right temporal cortex (Figure 1D), indicating early-stage tau deposition. At that time, the patient’s MMSE score had declined slightly to 24/30, reflecting a modest progression in global cognitive function.