Differential annualized rates of hippocampal subfields atrophy in aging and future Alzheimer’s clinical syndrome

Louis Nadal (1, 2) , Pierrick Coupé (3) , Catherine Helmer (4) , José V. Manjón (5) , Hélène Amieva (4) , François Tison (1) , Jean-François Dartigues (4) , Gwenaelle Catheline (6) , Vincent Planche (1, 2)

1 IMN - Institut des Maladies Neurodégénératives [Bordeaux]
2 Centre Mémoire de Ressources et de Recherches [Bordeaux]
3 PICTURA - Patch-based processing for medical and natural images
4 BPH - Bordeaux population health
5 ITACA
6 INCIA - Institut de Neurosciences cognitives et intégratives d'Aquitaine

Several studies have investigated the differential vulnerability of hippocampal subfields during aging and Alzheimer’s disease (AD). Results were often contradictory, mainly because these works were based on concatenations of cross-sectional measures in cohorts with different ages or stages of AD, in the absence of a longitudinal design. Here, we investigated 327 participants from a population-based cohort of non-demented older adults with a 14-year clinical follow-up. MRI at baseline and 4 years later were assessed to measure the annualized rates of hippocampal subfields atrophy in each participant using an automatic segmentation pipeline with subsequent quality-control. In the one hand, CA4-dentate gyrus was significantly more affected than the other subfields in the whole population (CA1-3: -0.68%/year; subiculum: -0.99%/year and CA4-DG: -1.39%/year; p<0.0001). In the other hand, the annualized rate of CA1-3 atrophy was associated with an increased risk of developing Alzheimer’s clinical syndrome over time, independently of age, gender, educational level and ApoE4 genotype (HR=2.0; IC95% 1.4-3.0). These results illustrate the natural history of hippocampal subfields atrophy during aging and AD by showing that the dentate gyrus is the most vulnerable subfield to the effects of aging while the cornu-ammonis is the primary target of AD pathophysiological processes, years prior to symptom onset.

Mots clés: MRI; Hippocampal subfields; aging; Alzheimer’s disease

Domaines: Neurosciences [q-bio.NC]; Imagerie médicale

Louis Nadal, Pierrick Coupé, Catherine Helmer, José V. Manjón, Hélène Amieva, et al.. Differential annualized rates of hippocampal subfields atrophy in aging and future Alzheimer’s clinical syndrome. Neurobiology of Aging, In press, ⟨10.1016/j.neurobiolaging.2020.01.011⟩. ⟨hal-02481530⟩