Iron Level and Myelin Content in the Ventral Striatum Predict Memory Performance in the Aging Brain

Abstract

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.

Relationship between aging and T1 relaxation time in deep gray matter: A voxel‐based analysis

“…Previous studies suggested that R2* values in the ventral striatum increase with aging as a result of iron accumulation, as observed by T 1 shortening. Although it is not easy to correlate specific brain structure changes with specific brain functions due to the heterogeneity of these structures, Steiger et al demonstrated that higher iron levels within the ventral striatum predicts memory performance . The nucleus accumbens is a part of the limbic circuit and is involved in both motivation and memory functions, which tend to decrease with aging.…”

“…36 A monotonous decline in T 1 relaxation time was observed in the nucleus accumbens in this study. Previous studies suggested that R2* values in the ventral striatum increase with aging as a result of iron accumulation, 26,37 as observed by T 1 shortening. Although it is not easy to correlate specific brain structure changes with specific brain functions due to the heterogeneity of these structures, Steiger et al demonstrated that higher iron levels within the ventral striatum predicts memory performance.…”

Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly

“…Data from this group of elderly participants have already been published (Steiger et al, 2016). This study was carried out in accordance with the recommendations of the local ethics committee (Medical Association Hamburg).…”

“…We took advantage of structural MRI data for all elderly (but not young) participants acquired in a separately conducted study using a 3T MR system (Siemens Trio) with a standard 32-channel head coil as described in Steiger et al (2016). Briefly, whole-brain multiparameter mapping (MPM; Draganski et al, 2011) was conducted on the basis of multi-echo 3D FLASH (fast low angle shot) images at 1 mm isotropic resolution with predominantly proton density (PD), magnetization transfer (MT) or T 1 weighting.…”

All Wrapped Up: Environmental Effects on Myelination

“…In models of MS, MRI and histological iron distribution reveal that iron maintains myelin integrity and plays an important role in remyelination and repair [151]. Interestingly, age-related iron accumulation in the striatum is linked to demyelination and a reduction in declarative memory [152]. This indicates both a pathogenic and reparative role for iron in OL activity and integrity…”