Amygdala atrophy is prominent in Alzheimer’s disease and relates to symptom severity

Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Psychiatry Research (Impact Factor: 2.47). 09/2011; 194(1):7-13. DOI: 10.1016/j.pscychresns.2011.06.014
Source: PubMed


Despite numerous studies on the role of medial temporal lobe structures in Alzheimer's disease (AD), the magnitude and clinical significance of amygdala atrophy have been relatively sparsely investigated. In this study, we used magnetic resonance imaging (MRI) to compare the level of amygdala atrophy to that of the hippocampus in very mild and mild AD subjects in two large samples (Sample 1 n=90; Sample 2 n=174). Using a series of linear regression analyses, we investigated whether amygdala atrophy is related to global cognitive functioning (Clinical Dementia Rating Sum of Boxes: CDR-SB; Mini Mental State Examination: MMSE) and neuropsychiatric status. Results indicated that amygdala atrophy was comparable to hippocampal atrophy in both samples. MMSE and CDR-SB were strongly related to amygdala atrophy, with amygdala atrophy predicting MMSE scores as well as hippocampal atrophy, but predicting CDR-SB scores less robustly. Amygdala atrophy was related to aberrant motor behavior, with potential relationships to anxiety and irritability. These results suggest that the magnitude of amygdala atrophy is comparable to that of the hippocampus in the earliest clinical stages of AD, and is related to global illness severity. There also appear to be specific relationships between the level of amygdala atrophy and neuropsychiatric symptoms that deserve further investigation.

Download full-text


Available from: Bradford Dickerson, Dec 13, 2013
36 Reads
  • Source
    • "Over the last couple of decades, multiple studies have provided evidence of anatomical differences between control groups and cognitively impaired groups at the population level, for a collection of diseases, including schizophrenia, depression, Huntington's or dementia [16] [8] [4] [17] [26] [19] [1] [13] [18] [24] [14]. In the particular case of neuro-degenerative diseases, a repeated objective has been to design anatomical biomarkers, measurable from imaging data, that would allow for individualized detection and prediction of the disease. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Diffeomorphic registration using optimal control on the diffeomorphism group and on shape spaces has become widely used since the development of the Large Deformation Diffeomorphic Metric Mapping (LDDMM) algorithm. More recently, a series of algorithms involving sub-riemannian constraints have been introduced, in which the velocity fields that control the shapes in the LDDMM framework are constrained in accordance with a specific deformation model. Here, we extend this setting by considering, for the first time, inequality constraints, in order to estimate surface deformations that only allow for atrophy, introducing for this purpose an algorithm that uses the augmented lagrangian method. We also provide a version of our approach that uses a weaker constraint in which only the total volume is forced to decrease. These developments are illustrated by numerical experiments on brain data.
  • Source
    • "The functional connectivity patterns of the subdivisions of the amygdala should be evaluated in the future. The gray matter volume has been found to be atrophied (Basso et al., 2006; Poulin et al., 2011; Whitwell et al., 2007), and the connectivity patterns have been found to be disrupted (Xie et al., 2012; Yao et al., 2013), in the amygdala of AD/MCI subjects. These impairments of the amygdala may be biomarkers for the diagnosis of MCI. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mild cognitive impairment (MCI) is considered to be the prodromal stage of Alzheimer's disease (AD). The amygdala, which is considered to be a hub, has been shown to have widespread brain connections with many cortical regions. Longitudinal alterations in the functional connectivity of the amygdala remain unclear in MCI. We hypothesized that the impairment in the amygdala-cortical loop would be more severe in a follow-up MCI group than in a baseline MCI group and that these alterations would be related to the disease processes. To test this hypothesis, we used resting-state functional MRI to investigate alterations in amygdalar connectivity patterns based on longitudinal data from 13 MCI subjects (8 males and 5 females). Compared to the baseline, decreases in functional connectivity were mainly found located between the amygdala and regions at the conjunction of the temporal-occipital system and the regions included in the default mode network in the follow-up MCI individuals. The alterations in the functional connectivity of the identified regions were validated in an independent dataset. Specifically, reduced amygdalar connectivity was significantly correlated with cognitive abilities. These findings indicate that impairments in the functional connectivity of the amygdala may be potential biomarkers of the progression of MCI.
    Brain Connectivity 05/2014; 4(5). DOI:10.1089/brain.2014.0223
  • Source
    • "The amygdala is also impacted by AD, and atrophy in this region is comparable to hippocampal atrophy in early stages of the disease [30]. Furthermore, emotional event memory has been more highly correlated to amygdalar damage than hippocampal volume [31]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The human apolipoprotein ε4 allele (APOE4) has been implicated as one of the strongest genetic risk factors associated with Alzheimer's disease (AD) and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR) mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX) mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD.
    PLoS ONE 04/2014; 9(4):e94071. DOI:10.1371/journal.pone.0094071 · 3.23 Impact Factor
Show more