Changes of hippocampal N-acetyl aspartate and volume in Alzheimer's disease

Schuff, Norbert; Amend, Diane; Ezekiel, Frank; Steinman, S.; Tanabe, Jody; Norman, David; Jagust, W.J.; Kramer, J. H.; Mastrianni, James A.; Fein, George; Weiner, M W

doi:10.1212/wnl.49.6.1513

Cited by 192 publications

(147 citation statements)

References 16 publications

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“…First, the magnitude of the NAA reduction is very similar to that, which we previously reported for patients with Alzheimer's dementia (20) . Notwithstanding this similarity of NAA reductions, our PTSD patients showed no gross cognitive memory impairments.…”

Section: Naa In Post Traumatic Stress Disorder (Ptsd)supporting

confidence: 86%

“…Notwithstanding this similarity of NAA reductions, our PTSD patients showed no gross cognitive memory impairments. Second, hippocampal NAA reductions in Alzheimer's disease were accompanied by substantial hippocampal volume losses in the range from 20% to 40% (20) . Another explanation for NAA decrease in PTSD is impaired metabolism of neuronal processes, resulting in secondary NAA loss.…”

Section: Naa In Post Traumatic Stress Disorder (Ptsd)mentioning

confidence: 98%

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N-Acetylaspartate as a Marker of Neuronal Injury in Neurodegenerative Disease

Schuff¹,

Meyerhoff²,

Mueller³

et al.

Advances in Experimental Medicine and Biology

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Considerable evidence suggests that normal aging is associated with gradual impairment of memory functioning [1]. The medial temporal lobe, especially the hippocampus, plays a central role in declarative memory processing [2]. However, magnetic resonance imaging (MRI) studies have produced controversial results concerning the age-related hippocampal volume loss, which could be due in part to the non-specificity of volume shrinkage as an indicator for neuron loss. In contrast to volume, NAA is generally considered a marker for viable neurons, because NAA reaches detectable concentrations only in neuronal tissue but not in other brain tissues, including glial cells. Using proton magnetic resonance spectroscopic imaging ( 1 H MRSI) and MRI together, we studied hippocampal metabolites and volumes in 24 healthy adults from 36 to 85 years of age. Our goals were to test whether NAA levels vary in the hippocampus as a function of normal aging and 2) to determine the relationship between hippocampal NAA and volume changes. We found NAA/Cho ratios decreased by 24% (r = −0.53, p = 0.01) and NAA/Cr ratios decreased by 26% (r = −0.61, p < 0.005) over the age range studied, while Cho/Cr remained stable, implying diminished NAA levels. In the same population, hippocampal volume shrank by 20% (r = −0.64, p < 0.05). The relationships of these measures with aging are depicted in Figure 1. Since NAA is considered a marker of neurons, these results provide stronger support for neuron loss in the aging hippocampus than volume measurements by MRI alone.Since contributions to the NAA signal may arise from both gray and white matter tissue, it is critical to differentiate between metabolite changes of gray and white matter, and other tissue types. One approach for differentiation is the use of linear regressions to predict the relationship between metabolite intensity changes and gray/white matter variations in MRSI voxels (4,(8)(9)(10)(11)(12). However, most previous MRSI studies that used linear regression averaged metabolite concentrations over different lobes of the brain, ignoring regional variations. In addition, tissues other than gray and white matter were ignored or not determined, such as white matter lesions, which occur frequently in the aged brain. We developed an approach for obtaining metabolite concentrations of gray, white matter, as well as of white matter lesions in different lobes of the brain using linear regression. We applied the new technique to measure NAA concentrations in the frontal and the parietal lobe in 40 normal elderly subjects (56 to 89 years, mean age 74 ± 8, 22 female, 18 male). NAA was about 15% lower in cortical gray matter and 23% lower in white matter lesions when compared to normal white matter. Cr was 11% higher in cortical gray than in white matter, and also about 15% higher in the parietal cortex compared to the frontal cortex. Cho was 28% lower in cortical gray matter than in white matter. Furthermore, NAA and Cr changes correlated with age. The results suggest that in addition to the hippo...

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Section: Naa In Post Traumatic Stress Disorder (Ptsd)supporting

confidence: 86%

Section: Naa In Post Traumatic Stress Disorder (Ptsd)mentioning

confidence: 98%

N-Acetylaspartate as a Marker of Neuronal Injury in Neurodegenerative Disease

Schuff¹,

Meyerhoff²,

Mueller³

et al.

Advances in Experimental Medicine and Biology

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“…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).…”

Section: Biochemical Changesmentioning

confidence: 99%

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

et al. 2006

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The purpose of the current thesis was twofold: (1) to examine various factors that might be contributing to age-related learning and memory deficits specifically related to the hippocampus, and (2) to validate our rat model of aging, employing a multilevel analysis. We found age-related deficits on both spatial and non-spatial hippocampus-dependent tasks that were accompanied by structural alterations observed both in vivo (volume, but not neuronal metabolic function) and post mortem (neuronal density and neurogenesis, but not synaptic or mitochondrial density). Furthermore, our results suggest that the observed hippocampal structural changes, namely decreased volume and neurogenesis, predict learning and memory deficits, and both can be accounted for by neurogenic reduction. In addition, the above-mentioned pattern of age-related deficits closely resembles that seen in humans, suggesting the present rat version of aging to be a very useful model for investigating hippocampal aging in humans.

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“…In the manual method, boundaries of the hippocampus were drawn on the T1-weighted MR images using in-house-written software (19), following previously published guidelines that include the hippocampal proper, dentate gyrus, subiculum, fimbria, and alveus (20). Volumes were calculated by counting all pixels within the traced area and multiplying by the nominal MRI resolution.…”

Section: Volume Measurementsmentioning

confidence: 99%

Comparison of automated and manual MRI volumetry of hippocampus in normal aging and dementia

Hsu

Schuff

et al. 2002

Magnetic Resonance Imaging

192

151

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Purpose: To determine whether automatic and manual measurements of hippocampal volume differences on MRI between normal aging, cognitive impairment (CI), and Alzheimer's disease (AD) yield similar results. Materials and Methods:Reliability was determined for an automatic and a manual method on nine volunteers (22-83 years old) who underwent MRI twice in 1 day. Hippocampal volumes of 20 cognitively normal subjects (mean age 74.0 Ϯ 6.2 years) and age-matched patients (20 CI and 20 AD) were compared. Results:The intraclass correlation for automatic calculations of hippocampal volume was 0.94; for manual tracing it was 0.99. Volume differences between cognitively normal, CI, and AD subjects from the automatic and manual methods were similar. Conclusion:Because the automatic calculations were faster and less susceptible to rater bias than manual tracing, this automated method is expected to be very useful for analyzing hippocampal changes in studies of aging and dementia. 1,2). Most studies have used manual tracing of the hippocampus to determine volume changes; however, this approach requires extensive rater training and has a potential risk of rater bias. High-dimensional brain warping algorithms were developed that can be used to automatically mask the hippocampus on MRI data (3-5). Although such algorithms reduce to a large extent dependency on raters, automated marking can be more variable than manual procedures because of computational errors due to image noise, which compromise the reliability of the measurements. This could particularly be a problem for MRI studies of aging brain and dementia, because image contrast is often reduced with older brains. Therefore, the aim of this study was to compare the ability of automated and manual hippocampal volumetry in differentiating between normal aging, cognitive impairment (CI) (which could be an early stage of AD), and AD.AD is the most common cause of dementia in the elderly; it is characterized by neuron loss, especially involving the hippocampus (6). In accordance with pathological findings, a number of MRI studies have shown significant atrophy of the hippocampus in patients with AD (1,7,8). Hippocampal volume loss was also found in subjects with CI (9 -12) in the absence of clinical symptoms of dementia, and in cognitively normal subjects with genetic risks for AD (13,14). Furthermore, longitudinal studies suggest that hippocampal volume loss predicts cognitive decline (11,15). In this study, differences in hippocampal volumes among cognitively normal, CI, and AD subjects are determined using both manual and automatic procedures. MATERIALS AND METHODS SubjectsTo determine the reliability of manual and automated measurements of hippocampal volumes, nine volunteers (two males and seven females, 22-84 years of age, mean age 44 Ϯ 18 years) were recruited, and MR data were acquired twice from each subject on the same day in separate sessions.To compare manual and automated measurements of hippocampal volume loss in aging and dementia, MRI

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Changes of hippocampal N-acetyl aspartate and volume in Alzheimer's disease

Cited by 192 publications

References 16 publications

N-Acetylaspartate as a Marker of Neuronal Injury in Neurodegenerative Disease

N-Acetylaspartate as a Marker of Neuronal Injury in Neurodegenerative Disease

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

Comparison of automated and manual MRI volumetry of hippocampus in normal aging and dementia

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