Alzheimer Disease: Karas GB

Karas GB, Scheltens P, Rombouts SA, Visser PJ, van Schijndel RA, Fox NC, Barkhof F. · Department of Diagnostic Radiology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. · Neuroimage. · Pubmed #15488420 No free full text.

Abstract: PURPOSE: Mild cognitive impairment (MCI) is thought to be the prodromal phase to Alzheimer's disease (AD). We analyzed patterns of gray matter (GM) loss to examine what characterizes MCI and what determines the difference with AD. MATERIALS AND METHODS: Thirty-three subjects with AD, 14 normal elderly controls (NCLR), and 22 amnestic MCI subjects were included and underwent brain MR imaging. Global GM volume was assessed using segmentation and local GM volume was assessed using voxel-based morphometry (VBM); VBM was optimized for template mismatch and statistical mass. RESULTS: AD subjects had significantly (12.3%) lower mean global GM volume when compared to controls (517 +/- 58 vs. 590 +/- 52 ml; P < 0.001). Global GM volume in the MCI group (552 +/- 52) was intermediate between these two: 6.2% lower than AD and 6.5% higher than the controls but not significantly different from either group. VBM showed that subjects with MCI had significant local reductions in gray matter in the medial temporal lobe (MTL), the insula, and thalamus compared to NCLR subjects. By contrast, when compared to subjects with AD, MCI subjects had more GM in the parietal association areas and the anterior and the posterior cingulate. CONCLUSION: GM loss in the MTL characterizes MCI, while GM loss in the parietal and cingulate cortices might be a feature of AD.

Karas GB, Burton EJ, Rombouts SA, van Schijndel RA, O'Brien JT, Scheltens P, McKeith IG, Williams D, Ballard C, Barkhof F. · Department of Diagnostic Radiology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. · Neuroimage. · Pubmed #12725765 No free full text.

Abstract: Voxel-based morphometry (VBM) has already been applied to MRI scans of patients with Alzheimer's disease (AD). The results of these studies demonstrated atrophy of the hippocampus, temporal pole, and insula, but did not describe any global brain changes or atrophy of deep cerebral structures. We propose an optimized VBM method, which accounts for these shortcomings. Additional processing steps are incorporated in the method, to ensure that the whole spectrum of brain atrophy is visualized. A local group template was created to avoid registration bias, morphological opening was performed to eliminate cerebrospinal fluid voxel misclassifications, and volume preserving modulation was used to correct for local volume changes. Group differences were assessed and thresholded at P < 0.05 (corrected). Our results confirm earlier findings, but additionally we demonstrate global cortical atrophy with sparing of the sensorimotor cortex, occipital poles, and cerebellum. Moreover, we show atrophy of the caudate head nuclei and medial thalami. Our findings are in full agreement with the established neuropathological descriptions, offering a comprehensive view of atrophy patterns in AD.

Sluimer JD, van der Flier WM, Karas GB, Fox NC, Scheltens P, Barkhof F, Vrenken H. · Department of Diagnostic Radiology, Alzheimer Centre, Vrije Universiteit Medical Centre, Amsterdam, the Netherlands. · Radiology. · Pubmed #18574133 links to  free full text

Abstract: PURPOSE: To prospectively determine whole-brain atrophy rate in mild cognitive impairment (MCI) and Alzheimer disease (AD) and its association with cognitive decline, and investigate the risk of progression to dementia in initially nondemented patients given baseline brain volume and whole-brain atrophy rate. MATERIALS AND METHODS: This study was IRB approved; written informed consent was obtained; and included 65 AD patients (38 women, 27 men; age, 52-81 years), 45 MCI patients (22 women, 23 men; age, 56-80 years), 27 patients with subjective complaints (12 women, 15 men; age, 50-87 years), and 10 healthy controls (six women, four men; age, 53-80 years). Two magnetic resonance (MR) images were acquired at average interval of 1.8 years +/- 0.7 (standard deviation). Baseline brain volume and whole-brain atrophy rates were measured on three-dimensional T1-weighted MR images (1.0 T; single slab, 168 sections; matrix size, 256 x 256; field of view, 250 mm; voxel size, 1 x 1 x 1.5 mm; repetition time msec/echo time msec/inversion time msec, 15/7/300; and flip angle, 15 degrees ). Associations were assessed by using partial-correlations. Cox proportional hazards models were used to estimate risk of developing dementia. RESULTS: Baseline brain volume was lowest in AD but did not differ significantly between MCI, subjective complaints, and control groups (P > .38). Whole-brain atrophy rates were higher in AD (-1.9% per year +/- 0.9) than MCI (-1.2% per year +/- 0.9, P = .003) patients, who had higher whole-brain atrophy rates than patients with subjective complaints (-0.7% per year +/- 0.7, P = .03) and controls (-0.5% per year +/- 0.5, P = .05). Whole-brain atrophy rate correlated with annualized Mini-Mental State Examination (MMSE) change (r = 0.48, P < .001), while baseline volume did not (r = 0.11, P = .22). Cox models showed that-after correction for age, sex, and baseline MMSE-a higher whole-brain atrophy rate was associated with an increased risk of progression to dementia (highest vs lowest tertile [hazard ratio, 3.6; 95% confidence interval: 1.2, 11.4]). CONCLUSION: Whole-brain atrophy rate was strongly associated with cognitive decline. In nondemented participants, a high whole-brain atrophy rate was associated with an increased risk of progression to dementia.