Iron Level and Myelin Content in the Ventral Striatum Predict Memory Performance in the Aging Brain
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Iron Level and Myelin Content in the Ventral Striatum Predict Memory Performance in the Aging Brain. / Steiger, Tineke K; Weiskopf, Nikolaus; Bunzeck, Nico.
In: J NEUROSCI, Vol. 36, No. 12, 23.03.2016, p. 3552-8.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Iron Level and Myelin Content in the Ventral Striatum Predict Memory Performance in the Aging Brain
AU - Steiger, Tineke K
AU - Weiskopf, Nikolaus
AU - Bunzeck, Nico
N1 - Copyright © 2016 Steiger et al.
PY - 2016/3/23
Y1 - 2016/3/23
N2 - UNLABELLED: Age-related memory impairments have been associated with structural changes in the dopaminergic system, but the underlying mechanisms remain unclear. Recent work indicates that iron accumulation might be of particular relevance. As iron accumulates, a degeneration of myelin sheaths has been observed in the elderly, but the relationship between both and their impact on memory performance in healthy elderly humans remain important open questions. To address this issue, we combined an established behavioral paradigm to test memory performance [verbal learning memory test (VLMT)] with state of the art quantitative magnetic resonance imaging techniques allowing us to quantify the degree of myelination and iron accumulation via markers of tissue microstructure in a group of young (18-32 years) and healthy elderly humans (55-79 years). As expected, we observed a decrease in gray matter volume and myelin, and an increase of iron in the elderly relative to the young subjects within widespread brain regions, including the basal ganglia. Furthermore, higher levels of iron within the ventral striatum were accompanied by a negative correlation between myelin and iron specific for the elderly participants. Importantly, both markers of iron and myelin (and their ratio) predicted the performance of the elderly in the VLMT. This suggests that ventral striatum iron accumulation is linked to demyelination and impairments in declarative memory. Together, our data provide novel insights into underlying microstructural mechanisms of memory decline in the elderly.SIGNIFICANCE STATEMENT: Memory decline in healthy elderly is a common phenomenon, but the underlying neural mechanisms remain unclear. We used a novel approach that allowed us to combine behavior and whole-brain measures of iron, myelin, and gray matter in the participant's individual subspace to analyze structure-structure and structure-behavior interactions. We were able to show, that age-related high levels of iron are accompanied by a negative correlation of iron and myelin in the ventral striatum, which predicted individual memory performance. As such, our findings provide unprecedented insights into the basic mechanisms of memory decline in the elderly.
AB - UNLABELLED: Age-related memory impairments have been associated with structural changes in the dopaminergic system, but the underlying mechanisms remain unclear. Recent work indicates that iron accumulation might be of particular relevance. As iron accumulates, a degeneration of myelin sheaths has been observed in the elderly, but the relationship between both and their impact on memory performance in healthy elderly humans remain important open questions. To address this issue, we combined an established behavioral paradigm to test memory performance [verbal learning memory test (VLMT)] with state of the art quantitative magnetic resonance imaging techniques allowing us to quantify the degree of myelination and iron accumulation via markers of tissue microstructure in a group of young (18-32 years) and healthy elderly humans (55-79 years). As expected, we observed a decrease in gray matter volume and myelin, and an increase of iron in the elderly relative to the young subjects within widespread brain regions, including the basal ganglia. Furthermore, higher levels of iron within the ventral striatum were accompanied by a negative correlation between myelin and iron specific for the elderly participants. Importantly, both markers of iron and myelin (and their ratio) predicted the performance of the elderly in the VLMT. This suggests that ventral striatum iron accumulation is linked to demyelination and impairments in declarative memory. Together, our data provide novel insights into underlying microstructural mechanisms of memory decline in the elderly.SIGNIFICANCE STATEMENT: Memory decline in healthy elderly is a common phenomenon, but the underlying neural mechanisms remain unclear. We used a novel approach that allowed us to combine behavior and whole-brain measures of iron, myelin, and gray matter in the participant's individual subspace to analyze structure-structure and structure-behavior interactions. We were able to show, that age-related high levels of iron are accompanied by a negative correlation of iron and myelin in the ventral striatum, which predicted individual memory performance. As such, our findings provide unprecedented insights into the basic mechanisms of memory decline in the elderly.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aging
KW - Female
KW - Humans
KW - Iron
KW - Male
KW - Mental Recall
KW - Middle Aged
KW - Myelin Sheath
KW - Tissue Distribution
KW - Ventral Striatum
KW - Young Adult
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1523/JNEUROSCI.3617-15.2016
DO - 10.1523/JNEUROSCI.3617-15.2016
M3 - SCORING: Journal article
C2 - 27013683
VL - 36
SP - 3552
EP - 3558
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 12
ER -