The Aging Hippocampus: Cognitive, Biochemical and Structural Findings

Abstract

Aging is often accompanied by learning and memory problems, many of which resemble deficits associated with hippocampal damage. Studies of aging in nonhuman animals have demonstrated hippocampus-related memory decline, and point to a possible locus for impairments associated with normal and pathological aging in humans. Two well-characterized hippocampus-dependent tasks in nonhuman animal literature are the Morris water task (MWT) and the transverse patterning discrimination task (TPDT). We employed the virtual MWT and the TPDT to assess hippocampus-dependent cognition in humans. Magnetic resonance imaging and proton magnetic resonance spectroscopy were employed to measure hippocampal volume and neurochemistry respectively. Age-related deficits were observed in performance on both hippocampus-dependent tasks. This pattern of impairment was accompanied by decreased hippocampal NAA/Cre ratios and volume, both of which imply neuronal loss and/or decrease in neuronal density. Collectively, our results suggest that hippocampus undergoes structural and biochemical changes with normal aging and that these changes may represent an important component of age-related deterioration in hippocampus-dependent cognition.

The aging hippocampus: A multi-level analysis in the rat

“…Recent evidence indicates that elderly people are impaired in spatial navigation in virtual environments (Driscoll et al, 2003a(Driscoll et al, , 2003b(Driscoll et al, , 2005Laurance et al, 2002;Moffat and Resnick, 2002;Moffat et al, 2001). Taken together, the human imaging studies are consistent with the idea that the hippocampal formation contributes to the encoding and retrieval of topographical information in humans.…”

“…So far, the virtual Morris water task has proven useful in studying sex differences in place learning and memory (Astur et al, 1998aDriscoll et al, 2005), rules governing place learning (Hamilton and Sutherland 1999;Hamilton et al, 2002), deficits after hippocampal damage (Astur et al, 2002), aging (Driscoll et al, 2003a(Driscoll et al, , 2005Laurance et al, 2002;Moffat and Resnick, 2002), and fetal alcohol syndrome (FAS; Hamilton et al, 2003). Together, these studies demonstrate that successful spatial navigation in humans, as assessed by virtual navigation, is also highly dependent on the integrity of the hippocampal formation.…”

“…A human analog of the Morris water task for measuring hippocampal processes has been developed, however, using virtual navigation through computer-generated environments. Many virtual navigation tasks, such as a virtual arena (Jacobs et al, 1998), a virtual reality town (Maguire et al, 1998), a virtual maze (Moffat et al, 1998), a virtual Morris water task (Astur et al, 1998a;Astur et al, 2002;Driscoll et al, 2003aDriscoll et al, , 2005Hamilton and Sutherland, 1999;Hamilton et al, 2002;Hamilton et al, 2003;Moffat and Resnick, 2002), and a Hebb-Williams maze (Shore et al, 2001) have been developed to facilitate the testing of human navigational processes in a laboratory setting.…”

“…Consequently, it has been suggested that decrease in NAA values may also reflect the magnitude of neuronal injury and metabolic dysfunction. Decrease in NAA in the hippocampus has been reported in several conditions, including PTSD (Schuff et al, 1997a), epilepsy (Ende et al, 1997), Alzheimer's disease (Schuff et al, 1997b) and normal aging (Driscoll et al, 2003a(Driscoll et al, , 2005Schuff et al, 1999).…”

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

“…The hippocampus is necessary for explicit learning in humans, and hippocampal synapses exhibit robust forms of long‐lasting associative synaptic plasticity that appear necessary for certain forms of learning in animals (Burgess et al ., 2002). There have been numerous studies on the cellular and molecular mechanisms of cognitive impairment resulting from hippocampal aging and dysfunction (Driscoll et al ., 2003; Chételat et al ., 2013). Hippocampal aging is associated with a little change in the hippocampal gross structure or volume; it is associated with biochemical changes in the expression of hundreds of genes involved in neuronal signaling and synaptic plasticity (Blalock et al ., 2003).…”