title: Longitudinal Evidence for Increased Functional Response in Frontal Cortex for Older Adults with Hippocampal Atrophy and Memory Decline.
abstract: The functional organization of the frontal cortex is dynamic. Age-related increases in frontal functional responses have been shown during various cognitive tasks, but the cross-sectional nature of most past studies makes it unclear whether these increases reflect reorganization or stable individual differences. Here, we followed 130 older individuals' cognitive trajectories over 20-25 years with repeated neuropsychological assessments every 5th year, and identified individuals with stable or declining episodic memory. Both groups displayed significant gray matter atrophy over 2 successive magnetic resonance imaging sessions 4 years apart, but the decline group also had a smaller volume of the right hippocampus. Only individuals with declining memory demonstrated increased prefrontal functional responses during memory encoding and retrieval over the 4-year interval. Regions with increased functional recruitment were located outside, or on the borders of core task-related networks, indicating an expansion of these over time. These longitudinal findings offer novel insight into the mechanisms behind age-associated memory loss, and are consistent with a theoretical model in which hippocampus atrophy, past a critical threshold, induces episodic-memory decline and altered prefrontal functional organization.
authors.affiliation: Department of Integrative Medical Biology, Umeå University, SE-901 87 Umeå, Sweden.|Umeå center for Functional Brain Imaging, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Pudas
authors.affiliation: Centre for Demographic and Ageing Research at Umeå University (CEDAR), Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Josefsson
authors.affiliation: Umeå center for Functional Brain Imaging, Umeå University, SE-901 87 Umeå, Sweden.|Department of Radiation Sciences, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rieckmann
authors.affiliation: Department of Integrative Medical Biology, Umeå University, SE-901 87 Umeå, Sweden.|Umeå center for Functional Brain Imaging, Umeå University, SE-901 87 Umeå, Sweden.|Department of Radiation Sciences, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Nyberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D000073216:Mental Status and Dementia Tests; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D013997:Time Factors
chemical_list: D010100:Oxygen
keywords: aging; fMRI; hippocampus; longitudinal study; memory decline; prefrontal cortex