We describe a new method to automatically discriminate between patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) and elderly controls, based on multidimensional classification ...of hippocampal shape features. This approach uses spherical harmonics (SPHARM) coefficients to model the shape of the hippocampi, which are segmented from magnetic resonance images (MRI) using a fully automatic method that we previously developed. SPHARM coefficients are used as features in a classification procedure based on support vector machines (SVM). The most relevant features for classification are selected using a bagging strategy. We evaluate the accuracy of our method in a group of 23 patients with AD (10 males, 13 females, age±standard-deviation (SD)=73±6 years, mini-mental score (MMS)=24.4±2.8), 23 patients with amnestic MCI (10 males, 13 females, age±SD=74±8 years, MMS=27.3±1.4) and 25 elderly healthy controls (13 males, 12 females, age±SD=64±8 years), using leave-one-out cross-validation. For AD vs controls, we obtain a correct classification rate of 94%, a sensitivity of 96%, and a specificity of 92%. For MCI vs controls, we obtain a classification rate of 83%, a sensitivity of 83%, and a specificity of 84%. This accuracy is superior to that of hippocampal volumetry and is comparable to recently published SVM-based whole-brain classification methods, which relied on a different strategy. This new method may become a useful tool to assist in the diagnosis of Alzheimer's disease.
Acetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer's disease (AD) dementia. Basal forebrain cholinergic system (BFCS) atrophy is reported to precede both ...entorhinal cortex atrophy and memory impairment in AD, challenging the traditional model of the temporal sequence of topographical pathology associated with AD. We studied the effect of one-year Donepezil treatment on the rate of BFCS atrophy in prodromal AD patients using a double-blind, randomized, placebo-controlled trial of Donepezil (10 mg/day). Reduced annual BFCS rates of atrophy were found in the Donepezil group compared to the Placebo treated arm. Secondary analyses on BFCS subregions demonstrated the largest treatment effects in the Nucleus Basalis of Meynert (NbM) and the medial septum/diagonal band (Ch1/2). Donepezil administered at a prodromal stage of AD seems to substantially reduce the rate of atrophy of the BFCS nuclei with highest concentration of cholinergic neurons projecting to the cortex (NbM), hippocampus and entorhinal cortex (Ch1/2).
Measuring the morphology of brain sulci has been recently proposed as a novel imaging approach in Alzheimer's disease (AD). We aimed to investigate the relevance of such an approach in AD, by ...exploring its (1) clinical relevance in comparison with traditional imaging methods, (2) relationship with amyloid deposition, (3) association with cognitive functions. Here, 51 patients (n = 32 mild cognitive impairment/mild dementia-AD, n = 19 moderate/severe dementia-AD) diagnosed according to clinical-biological criteria (CSF biomarkers and amyloid-PET) and 29 controls (with negative amyloid-PET) underwent neuropsychological and 3T-MRI examinations. Mean sulcal width (SW) and mean cortical thickness around the sulcus (CT-S) were automatically measured. We found higher SW and lower CT-S in patients with AD than in controls. These differences were more pronounced at later stages of the disease and provided the best diagnostic accuracies among the imaging markers. Correlations were not found between CT-S or SW and amyloid deposition but between specific cognitive functions and regional CT-S/SW in key associated regions. Sulcal morphology is a good supporting diagnosis tool that reflects the main cognitive impairments in AD. It could be considered as a good surrogate marker to evaluate the efficacy of new drugs.
•Examination of sulcal morphology alterations is a good diagnosis tool for Alzheimer's disease.•This imaging marker is more accurate than traditional imaging tools such as hippocampal volume.•Sulcal morphology alterations are correlated to specific cognitive impairment observed.•Sulcal morphology alterations are related to disease severity.
BACKGROUND/OBJECTIVES
Cognitive decline associated with impaired kidney function might involve neurodegeneration. Our objectives were to evaluate the longitudinal association between kidney function ...and cognitive decline in older adults and to assess the involvement of cortical beta‐amyloid and hippocampal atrophy (features of Alzheimer's disease (AD)) in this association.
DESIGN
Secondary analysis of the randomized controlled Multidomain Alzheimer Preventive Trial (MAPT).
SETTINGS
Thirteen memory centers (France and Monaco, 2008–2016).
PARTICIPANTS
A total of 1,334 community‐dwellers >70 years old without dementia at baseline.
MEASUREMENTS
We estimated glomerular filtration rate (eGFR) from serum creatinine using CKD‐Epi equation. Cognition was assessed at baseline, 6, 12, 24, 36, 48, and 60 months using a composite Z‐score designed for MAPT. The Clinical Dementia Rating (CDR) score was used to assess cognition and functional independence. We examined the association between eGFR and (1) evolution of the composite cognitive Z‐score using mixed‐effect models and (2) progression on CDR using Cox models and mixed‐effect models. Adjustments were made for age, sex, education, ApoE genotype, cardiovascular risk factors and disease, hippocampal volume (measured with magnetic resonance), and cortical beta‐amyloid (measured with positron emission tomography).
RESULTS
Median (IQR) eGFR was 73(60–84) mL/min/1.73 m2. Two hundred sixty‐nine participants experienced progression on CDR score during follow‐up. eGFR<60 was significantly associated with progression on CDR score (adjusted hazard ratio (aHR) = 1.35, 95% CI 1.01–1.80) and with both the cognitive and functional independence components of CDR, but not with the evolution of the composite cognitive Z‐score (adjusted β‐coefficient −0.004, 95% CI −0.014; 0.006). Associations were not modified after further adjustment for beta‐amyloid (subsample: n = 252) and hippocampal volume (subsample: n = 270).
CONCLUSIONS
We did not find a mild to moderate renal insufficiency to be associated with brain imaging features of AD, and our results do not support the involvement of AD mechanisms in the incidence of cognitive impairment and functional decline associated with chronic kidney disease.
Data on 2,045 non-demented individuals with memory complaints were drawn from the Memento cohort study to examine the association between Apolipoprotein E ε4 allele (APOE4) and regional brain gray ...matter volumes. Linear regression was used to examine the association of APOE4 and measures of regional gray matter volumes in cross-sectional analysis and change therein using longitudinal analyses based on two brain MRI performed at baseline and at two-year follow-up. Overall, in analyses adjusted for age, sex, and intracranial volume, the presence of APOE4 was associated with lower total gray matter volume at baseline and with a higher atrophy rate over the follow-up. The hippocampus and entorhinal cortex were the two gray matter regions most associated with APOE4. Further adjustment for cardiovascular risk factors had little impact on these associations. There was an interaction between age, APOE4 status and total brain volume atrophy rate, with evidence of an earlier age at onset of atrophy in hippocampal volume in APOE4 carriers compared to non-carriers. Those results are in accordance with the role of medial temporal structures in the greater risk of dementia observed in people carrying the APOE4 allele.
According to meta-analyses, depression is associated with a smaller hippocampus. Most magnetic resonance imaging (MRI) studies among middle aged acute depressed patients are based on manual ...segmentation of the hippocampus. Few studies used automated methods such as voxel-based morphometry (VBM) or automated segmentation that can overcome certain drawbacks of manual segmentation (essentially intra- and inter-rater variability and operator time consumption).
The aim of our study was to compare the sensitivity of manual segmentation, automated segmentation and VBM to detect hippocampal structural changes in middle aged acute depressed population.
Twenty-one middle aged depressed inpatients and 21 matched controls were compared regarding their hippocampal structure using VBM with SPM5, manual segmentation and an automated segmentation algorithm. The VBM-ROI analysis was performed using two different normalization methods: the standard approach implemented in SPM5 and the most recent DARTEL algorithm.
Using VBM-DARTEL, when corrected for multiple comparisons, significant volume differences were detected between groups in different regions and more specifically in hippocampus with ROI analyses. Whereas using standard VBM (without DARTEL), ROI analyses did not show bilateral volume between group differences.
Significant hippocampal volume reductions between patients and controls were also detected using manual segmentation (−
11.6% volume reduction,
p
<
0.05) and automated segmentation (−
9.7% volume reduction,
p
<
0.05). VBM-DARTEL and automated segmentation show equal sensitivity in detecting hippocampal differences in depressed patients, while standard VBM was unable to detect hippocampal changes. Both VBM-DARTEL and automated segmentation could be used to perform large scale volumetric studies in humans. The new automated segmentation technique could further explore and detect hippocampal subpart differences that could be very useful for clarifying physiopathology of psychiatric disorders.
To prospectively evaluate the accuracy of automated hippocampal volumetry to help distinguish between patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and elderly ...controls, by using established criteria for patients with AD and MCI as the reference standard.
The regional ethics committee approved the study and written informed consent was obtained from all participants. The study included 25 patients with AD (11 men, 14 women; mean age +/- standard deviation SD, 73 years +/- 6; Mini-Mental State Examination (MMSE) score, 24.4 +/- 2.7), 24 patients with amnestic MCI (10 men, 14 women; mean age +/- SD, 74 years +/- 8; MMSE score, 27.2 +/- 1.4) and 25 elderly healthy controls (13 men, 12 women; mean age +/- SD, 64 years +/- 8). For each participant, the hippocampi were automatically segmented on three-dimensional T1-weighted magnetic resonance (MR) images with high spatial resolution. Segmentation was performed by using recently developed software that allows fast segmentation with minimal user input. Group differences in hippocampal volume were assessed by using Student t tests. To obtain robust estimates of P values, the correct classification rate, sensitivity, and specificity, bootstrap methods were used.
Significant hippocampal volume reductions were detected in all groups of patients (-32% in AD patients vs controls, P < .001; -19% in MCI patients vs controls, P < .001; and -15% in AD patients vs MCI patients, P < .01). Individual classification on the basis of hippocampal volume resulted in 84% correct classification (sensitivity, 84%; specificity, 84%) between AD patients and controls and 73% correct classification (sensitivity, 75%; specificity, 70%) between MCI patients and controls.
This automated method can serve as an alternative to manual tracing and may thus prove useful in assisting with the diagnosis of AD.
There is a growing need for surrogate biomarkers for Parkinson's disease (PD). Structural analysis using magnetic resonance imaging with T1-weighted sequences has the potential to quantify ...histopathological changes. Degeneration is typically measured by the volume and shape of morphological changes. However, these changes appear late in the disease, preventing their use as surrogate markers. We investigated texture changes in 108 individuals, divided into three groups, matched in terms of sex and age: (1) healthy controls (n = 32); (2) patients with early-stage PD (n = 39); and (3) patients with late-stage PD and severe L-dopa-related complications (n = 37). All patients were assessed in off-treatment conditions. Statistical analysis of first- and second-order texture features was conducted in the substantia nigra, striatum, thalamus and sub-thalamic nucleus. Regions of interest volumetry and voxel-based morphometry were performed for comparison. Significantly different texture features were observed between the three populations, with some showing a gradual linear progression between the groups. The volumetric changes in the two PD patient groups were not significantly different. Texture features were significantly associated with clinical scores for motor handicap. These results suggest that texture features, measured in the nigrostriatal pathway at PD diagnosis, may be useful in predicting clinical progression of motor handicap.
Amygdala is a key brain region for face perception. While the role of amygdala in the perception of facial emotion and gaze has been extensively highlighted with fMRI, the unfolding in time of ...amydgala responses to emotional versus neutral faces with different gaze directions is scarcely known.
Here we addressed this question in healthy subjects using MEG combined with an original source imaging method based on individual amygdala volume segmentation and the localization of sources in the amygdala volume. We found an early peak of amygdala activity that was enhanced for fearful relative to neutral faces between 130 and 170 ms. The effect of emotion was again significant in a later time range (310-350 ms). Moreover, the amygdala response was greater for direct relative averted gaze between 190 and 350 ms, and this effect was selective of fearful faces in the right amygdala.
Altogether, our results show that the amygdala is involved in the processing and integration of emotion and gaze cues from faces in different time ranges, thus underlining its role in multiple stages of face perception.
To evaluate the relationship of white matter hyperintensities (WMH) with decline in lower extremity function (LEF) over approximately 3 years in dementia-free older adults with memory complaints.
We ...obtained brain MRI data from 458 community-dwelling adults, aged 70 years or over, at baseline, and from 358 adults over an average follow-up of 963 days. We evaluated LEF using the Short Physical Performance Battery (SPPB). We related baseline WMH volumes and progression to SPPB scores over time, using mixed-effect linear regressions. For the secondary analyses, we categorized baseline WMH volume into quartiles, and dichotomized the WMH progression to compare fast and slow progression.
Baseline WMH volume (β = -0.017, 95% confidence interval CI -0.025 to -0.009), as well as WMH progression (β = -0.002, 95% CI -0.003 to -0.001), significantly associated with a decline in SPPB performance in adjusted analyses. Compared with the lowest quartile of baseline WMH volume, the highest quartile associated with a decline in SPPB performance (β = -0.301, 95% CI -0.558 to -0.044). Fast progression also associated with a decline in SPPB performance. We found clinically meaningful differences in the SPPB, with higher scores in participants with slow progression of WMH, at both 24 and 36 months.
Baseline level and WMH progression associated with longitudinal decline in SPPB performance among older adults. We detected clinically meaningful differences in SPPB performance on comparing fast with slow progression of WMH, suggesting that speed of WMH progression is an important determinant of LEF during aging.
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