title: Age-related cognitive decline coincides with accelerated volume loss of the dorsal but not ventral hippocampus in mice.
abstract: Even in the absence of neurodegenerative diseases, progressing age often coincides with cognitive decline and morphological changes. However, longitudinal studies that directly link these two processes are missing. In this proof-of-concept study we therefore performed repeated within-subject testing of healthy male R26R mice in a spatial learning task in combination with manganese-enhanced volumetric MRI analyses at the ages of 8, 16, and 24 months. We grouped the mice into good and poor performers (n = 6, each), based on their spatial learning abilities at the age of 24 months. Using this stratification, we failed to detect a priori volume differences, but observed a significant decrease in total hippocampal volume over time for both groups. Interestingly, this volume decrease was specific for the dorsal hippocampus and significantly accelerated in poor performers between 16 and 24 months of age. This is the first time that individual changes in hippocampal volume were traced alongside cognitive performance within the same subjects over 1½ years. Our study points to a causal link between volume loss of the dorsal hippocampus and cognitive impairments. In addition, it suggests accelerated degenerative processes rather than a priori volume differences as determining trajectories of age-related cognitive decline. Despite the relatively small sample sizes, the strong behavioral and moderate morphological alterations demonstrate the general feasibility of longitudinal studies of age-related decline in cognition and hippocampus integrity. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Reichel
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.|Core Unit Neuroimaging, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: B T
authors.initials: BT
authors.lastname: Bedenk
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.|Core Unit Neuroimaging, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Czisch
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: C T
authors.initials: CT
authors.lastname: Wotjak
mesh_terms: D000818:Animals; D000066492:Cognitive Aging; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000209:etiology; D003287:Contrast Media; D006624:Hippocampus / Q000000981:diagnostic imaging*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese; D018782:Maze Learning; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D009929:Organ Size; D000075082:Proof of Concept Study; D065852:Spatial Memory
chemical_list: D003287:Contrast Media; D008345:Manganese
keywords: ageing; cognitive impairments; hippocampus; memory; spatial learning; volumetry