Shannon Buckley

Voxel-based optimized morphometry (VBM) of gray and white matter in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis.

Summary:  Purpose: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE‐MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE‐no). In this study, we used optimized voxel‐based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE‐MTS and TLE‐no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE‐MTS and TLE‐no.

ASL Perfusion MRI Predicts Cognitive Decline and Conversion From MCI to Dementia

We compared the predictive value of cerebral perfusion as measured by arterial-spin labeling magnetic resonance imaging (ASL-MRI) with MRI-derived hippocampal volume for determining future cognitive and functional decline and subsequent conversion from mild cognitive impairment to dementia. Forty-eight mild cognitive impairment subjects received structural and ASL-MRI scans at baseline and clinical and neuropsychologic assessments annually. Thirteen subjects became demented during the period of longitudinal observation (2.7±1.0 y). Cox regression analyses suggest that baseline hippocampal volume [relative risk (RR)=0.99, P=0.004], baseline right inferior parietal (RR=0.64, P=0.01) and right middle frontal (RR=0.73, P=0.01) perfusion were associated with conversion to dementia. Results from linear mixed effects modeling suggest that baseline perfusion from the right precuneus predicted subsequent declines in Clinical Dementia Rating Sum of Boxes (P=0.002), Functional Activates Questionnaire (P=0.01), and selective attention (ie, Stroop switching, P=0.009) whereas baseline perfusion from the right middle frontal cortex predicted subsequent episodic memory decline (ie, total recognition discriminability score from the California Verbal Learning Test, P=0.03). These results suggest that hypoperfusion as detected by ASL-MRI can predict subsequent clinical, functional, and cognitive decline and may be useful for identifying candidates for future Alzheimer disease treatment trials.

Brain atrophy associated with baseline and longitudinal measures of cognition

The overall goal was to identify patterns of brain atrophy associated with cognitive impairment and future cognitive decline in non-demented elders. Seventy-one participants were studied with structural MRI and neuropsychological testing at baseline and 1-year follow-up. Deformation-based morphometry was used to examine the relationship between regional baseline brain tissue volume with baseline and longitudinal measures of delayed verbal memory, semantic memory, and executive function. Smaller right hippocampal and entorhinal cortex (ERC) volumes at baseline were associated with worse delayed verbal memory performance at baseline while smaller left ERC volume was associated with greater longitudinal decline. Smaller left superior temporal cortex at baseline was associated with worse semantic memory at baseline, while smaller left temporal white and gray matter volumes were associated with greater semantic memory decline. Increased CSF and smaller frontal lobe volumes were associated with impaired executive function at baseline and greater longitudinal executive decline. These findings suggest that baseline volumes of prefrontal and temporal regions may underlie continuing cognitive decline due to aging, pathology, or both in non-demented elderly individuals.

Diffusion tensor imaging of the nigrostriatal fibers in Parkinson's disease

Parkinsons disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars compacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregulation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to 1) develop a diffusion tensor tractography protocol for reliably tracking the nigrostriatal fibers on multicenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; and 3) test whether abnormal integrities of the nigrostriatal fibers in PD patients are associated with the severity of motor disability and putaminal dopamine binding ratios.

Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria

We sought to determine whether there are structural and metabolic changes in the brains of older adults with cognitive complaints yet who do not meet MCI criteria (i.e., preMCI). We compared the volumes of regional lobar gray matter (GM) and medial temporal lobe structures, including the hippocampus, entorhinal cortex (ERC), fusiform and parahippocampal gyri, and metabolite ratios from the posterior cingulate in individuals who had a Clinical Demetia Rating (CDR) of 0.5, but who did not meet MCI criteria (preMCI, N=17), patients with mild cognitive impairment (MCI, N=13), and cognitively normal controls (N=18). Controls had more ERC, fusiform, and frontal gray matter volume than preMCI and MCI subjects and greater parahippocampal volume and more posterior cingulate N-acetylaspartate (NAA)/myoinosotil (mI) than MCI. There were no significant differences between MCI and preMCI subjects on any of these measures. These findings suggest there are neurodegenerative changes in the brains of older adults who have cognitive complaints severe enough to qualify for CDR=0.5 yet show no deficits on formal neuropsychological testing. The results further support the hypothesis that detection of individuals with very mild forms of Alzheimers disease (AD) may be facilitated by use of the CDR, which emphasizes changes in cognition over time within individuals rather than comparison with group norms.

Brain Amyloid-β Burden Is Associated with Disruption of Intrinsic Functional Connectivity within the Medial Temporal Lobe in Cognitively Normal Elderly

The medial temporal lobe is implicated as a key brain region involved in the pathogenesis of Alzheimers disease (AD) and consequent memory loss. Tau tangle aggregation in this region may develop concurrently with cortical Aβ deposition in preclinical AD, but the pathological relationship between tau and Aβ remains unclear. We used task-free fMRI with a focus on the medical temporal lobe, together with Aβ PET imaging, in cognitively normal elderly human participants. We found that cortical Aβ load was related to disrupted intrinsic functional connectivity of the perirhinal cortex, which is typically the first brain region affected by tauopathies in AD. There was no concurrent association of cortical Aβ load with cognitive performance or brain atrophy. These findings suggest that dysfunction in the medial temporal lobe may represent a very early sign of preclinical AD and may predict future memory loss.

Diffusion Imaging of Nigral Alterations in Early Parkinson's Disease With Dopaminergic Deficits

This study reports the baseline characteristics of diffusion tensor imaging data in Parkinsons disease (PD) patients and healthy control subjects from the Parkinsons Progression Markers Initiative. The main goals were to replicate previous findings of abnormal diffusion imaging values from the substantia nigra. in a large multicenter cohort and determine whether nigral diffusion alterations are associated with dopamine deficits.

Are hippocampal size differences in posttraumatic stress disorder mediated by sleep pathology

Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as has been demonstrated by meta‐analyses. Proposed mechanistic relationships are reviewed briefly, including the hypothesis that sleep disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this includes findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition. We present results of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated with lower hippocampal volume. We outline a broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume.

Paroxysmal disturbances of functional connectivity in amyloid positive, cognitively intact elderlies

the hub region away from posterior regions in the higher frequency bands. This indicates a loss of relative functional importance of the posterior brain regions and posterior functional hubs are thus disproportionally affected. Conclusions: Concluding, we observed a gradually decreasing functional connectivity in posterior regions with increasing AD severity, which was accompanied by a shifted hub location from posterior to central regions.

Hippocampal subfields are superior to total hippocampal volume for the prediction of memory function and decline: A preliminary study

the longitudinal volume change. Finally, subfield-specific atrophy rates are obtained by integrating the Jacobian of this intra-subject transformation over each subfield. Results: Longitudinal atrophy is observed throughout the hippocampus, but greater on average in MCI than the control group. CA1 has significantly higher atrophy in MCI compared to controls (p1⁄40.02). The subfield label comprising stratum radiatum, stratum lacunosum-moleculare and vestigial hippocampal sulcus trends towards higher atrophy in MCI as well (p1⁄40.09). Atrophy in CA2/3 (p1⁄40.43) and DG (p1⁄40.67) do not differ significantly between the two groups. However, within the MCI group, subjects with ApoE4/E4 genotype (6 subjects) have significantly higher (p1⁄40.04) atrophy in CA2/3 than those with ApoE3/E3 (7 subjects) (Figure 2). Conclusions: Higher CA1 atrophy in MCI compared to controls and relative sparing of CA2/3 and DG have been reported by other researchers (Qiu et al., Neuroimage 40:1, 68-76; Apostolova et al., Arch. Neurol. 63:5, 693-699.). On the other hand, Mueller et al. found greater CA3 atrophy in subjects with ApoE4 genotype (Mueller et al., Neuroimage 42:1, 42-48). Our preliminary analysis replicates both of these results. This indicates that atlas-based subfield labeling techniques can potentially be used in clinical studies. However, the data set used is small and further validation in a larger data set is required. O2-01-06 HEAD SIZE, AGE AND GENDER ADJUSTMENT IN MRI STUDIES: A NECESSARY NUISANCE?