Associations between Genetic Risk for Alzheimer's Disease and Behavioral and Biochemical Brain Integrity in Healthy, Middle-Aged Adults
Mentor 1
Ira Driscoll
Location
Union Wisconsin Room
Start Date
29-4-2016 1:30 PM
End Date
29-4-2016 3:30 PM
Description
Both normal and pathological aging are accompanied by memory decline. The epsilon 4 (e4) allele of the apolipoprotein E (APOE) gene is the best established genetic risk factor for Alzheimer's disease (AD), behaviorally hallmarked by memory loss, yet there is still uncertainty as to the effects of APOE on cognitive function in normal aging. Here we focus our considerations on the hippocampus based on the fact that (1) the hippocampus is critically involved in memory, and (2) and is especially vulnerable to the deleterious effects of aging and early AD-related pathological processes. We employed a virtual analog of the Morris water task (WMT), a well-characterized hippocampus-dependent task in nonhuman literature, to assess spatial learning and memory. Proton magnetic resonance spectroscopy (1H MRS), a modality of MRI, was employed to measure neurochemical integrity of the hippocampus. Although in our sample of healthy, non-demented, middle-aged adults (N=150; age 40-60), APOE e4 carriers had higher hippocampal NAA (a marker of neuronal integrity) compared to non-carriers (p=0.04), there were no differences between APOE e4 carriers and non-carriers in spatial memory performance (p>0.05). We also report a significant relationship between spatial memory performance and right hippocampal NAA (p=0.04), and a non-significant trend for left hippocampal NAA (p=0.06), independent of APOE status. We found no correlation between hippocampal NAA and brain volume, which suggests that hippocampal NAA is potentially a more accurate measure of hippocampal integrity since NAA measures neuronal integrity and the volume measures a gross volume of the entire brain structure. No detectable differences in spatial memory performance were observed in this middle-aged, healthy sample, regardless of the genetic risk. Although seemingly unexpected, our finding of no differences or even a better neuronal integrity in e4 risk carriers are in line with the resource-modulation hypothesis which suggests that genetic effects on cognitive performance are magnified in old age, whereas they may be small or undetectable in younger adults (Lindenberger et al., 2008).
Associations between Genetic Risk for Alzheimer's Disease and Behavioral and Biochemical Brain Integrity in Healthy, Middle-Aged Adults
Union Wisconsin Room
Both normal and pathological aging are accompanied by memory decline. The epsilon 4 (e4) allele of the apolipoprotein E (APOE) gene is the best established genetic risk factor for Alzheimer's disease (AD), behaviorally hallmarked by memory loss, yet there is still uncertainty as to the effects of APOE on cognitive function in normal aging. Here we focus our considerations on the hippocampus based on the fact that (1) the hippocampus is critically involved in memory, and (2) and is especially vulnerable to the deleterious effects of aging and early AD-related pathological processes. We employed a virtual analog of the Morris water task (WMT), a well-characterized hippocampus-dependent task in nonhuman literature, to assess spatial learning and memory. Proton magnetic resonance spectroscopy (1H MRS), a modality of MRI, was employed to measure neurochemical integrity of the hippocampus. Although in our sample of healthy, non-demented, middle-aged adults (N=150; age 40-60), APOE e4 carriers had higher hippocampal NAA (a marker of neuronal integrity) compared to non-carriers (p=0.04), there were no differences between APOE e4 carriers and non-carriers in spatial memory performance (p>0.05). We also report a significant relationship between spatial memory performance and right hippocampal NAA (p=0.04), and a non-significant trend for left hippocampal NAA (p=0.06), independent of APOE status. We found no correlation between hippocampal NAA and brain volume, which suggests that hippocampal NAA is potentially a more accurate measure of hippocampal integrity since NAA measures neuronal integrity and the volume measures a gross volume of the entire brain structure. No detectable differences in spatial memory performance were observed in this middle-aged, healthy sample, regardless of the genetic risk. Although seemingly unexpected, our finding of no differences or even a better neuronal integrity in e4 risk carriers are in line with the resource-modulation hypothesis which suggests that genetic effects on cognitive performance are magnified in old age, whereas they may be small or undetectable in younger adults (Lindenberger et al., 2008).
