The A/T/N model applied through imaging biomarkers in a memory clinic.

PURPOSE: The A/T/N model is a research framework proposed to investigate Alzheimer's disease (AD) pathological bases (i.e., amyloidosis A, neurofibrillary tangles T, and neurodegeneration N). The application of this system on clinical populations is still limited. The aim of the study is to evaluate the topography of T distribution by 18F-flortaucipir PET in relation to A and N and to describe the A/T/N status through imaging biomarkers in memory clinic patients. METHODS: Eighty-one patients with subjective and objective cognitive impairment were classified as A+/A- and N+/N- through amyloid PET and structural MRI. Tau deposition was compared across A/N subgroups at voxel level. T status was defined through a global cut point based on A/N subgroups and subjects were categorized following the A/T/N model. RESULTS: A+N+ and A+N- subgroups showed higher tau burden compared to A-N- group, with A+N- showing significant deposition limited to the medial and lateral temporal regions. Global cut point discriminated A+N+ and A+N- from A-N- subjects. On A/T/N classification, 23% of patients showed a negative biomarker profile, 58% fell within the Alzheimer's continuum, and 19% of the sample was characterized by non-AD pathologic change. CONCLUSION: Medial and lateral temporal regions represent a site of significant tau accumulation in A+ subjects and possibly a useful marker of early clinical changes. This is the first study in which the A/T/N model is applied using 18F-flortaucipir PET in a memory clinic population. The majority of patients showed a profile consistent with the Alzheimer's continuum, while a minor percentage showed a profile suggestive of possible other neurodegenerative diseases. These results support the applicability of the A/T/N model in clinical practice.

Cortical Superficial Siderosis: A Descriptive Analysis in a Memory Clinic Population.

BACKGROUND: Cortical superficial siderosis (cSS) is a hemorrhagic marker of blood-brain barrier disruption detected in brain MRI. Together with cerebral microbleeds (CMB), they are recognized as a small vessel disease marker associated with cerebral amyloid angiopathy. OBJECTIVE: This study aims to determine the prevalence and the characteristics of cSS in a memory clinic population. METHODS: Cross-sectional retrospective analysis of 613 patients from Geneva University Hospitals memory clinic. All patients underwent standardized brain MRI and neuropsychological assessment with diagnosis confirmed by an expert. The presence of cSS was visually assessed and classified as focal (restricted to 3 sulci) or disseminated within the correspondent topography. CMB were classified according to the Microbleed Anatomical Rating Scale. RESULTS: cSS was detected in 26/613 patients (4.2%), classified as disseminated in 5/26 cases (19%). Alzheimer's disease (AD) and AD associated with a significant vascular component were the diagnoses more frequently related to cSS (18/26; 69%). Patients with cSS had an increased prevalence of both hypertension (81% versus 57%; p = 0.015) and WMH burden (p = 0.012). The overall prevalence of cerebral microbleeds (69% versus 32%; p < 0.01), as well as their mean number (0.69±0.47 versus 0.32±0.46; p < 0.01) were both increased in patients with cSS. In the logistic regression model, the presence of 5 or more CMB (OR 11.35; 95% CI 4.68-27.55; p < 0.01) and hypertension (OR 3.31; 95% CI 1.19-9.15; p = 0.021) were significantly associated with cSS. CONCLUSIONS: cSS is observed in patients diagnosed with AD and AD with a vascular component, being independently associated with multiple CMB and hypertension.