Sulcal Width Research Articles

The interplay of age, gender and amyloid on brain and cognition in mid-life and older adults

Deficits in memory are seen as a canonical sign of aging and a prodrome to dementia in older adults. However, our understanding of age-related cognition and brain morphology occurring throughout a broader spectrum of adulthood remains limited. We quantified the relationship between cognitive function and brain morphology (sulcal width, SW) using three cross-sectional observational datasets (PISA, AIBL, ADNI) from mid-life to older adulthood, assessing the influence of age, sex, amyloid (Aβ) and genetic risk for dementia. The data comprised cognitive, genetic and neuroimaging measures of a total of 1570 non-clinical mid-life and older adults (mean age 72, range 49–90 years, 1330 males) and 1365 age- and sex-matched adults with mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Among non-clinical adults, we found robust modes of co-variation between regional SW and multidomain cognitive function that differed between the mid-life and older age range. These cortical and cognitive profiles derived from healthy cohorts predicted out-of-sample AD and MCI. Furthermore, Aβ-deposition and educational attainment levels were associated with cognition but not SW. These findings underscoring the complex interplay between factors influencing cognition and brain structure from mid-life onwards, providing valuable insights for future research into neurodegeneration and the development of future screening algorithms.

A central role of sulcal width in the associations of sleep duration and depression with cognition in mid to late life.

Evidence suggests that poor sleep impacts cognition, brain health, and dementia risk but the nature of the association is poorly understood. This study examined how self-reported sleep duration, napping, and subjective depression symptoms are associated with the brain-cognition relationship in older adults, using sulcal width as a measure of relative brain health. A canonical partial least squares analysis was used to obtain two composite variables that relate cognition and sulcal width in a cross-sectional study of 137 adults aged 46-72. We used a combination of ANCOVA and path analyses to test the associations of self-reported sleep duration, napping, and subjective depression symptoms with the brain-cognition relationship. We observed a significant main effect of sleep duration on sulcal width, with participants reporting 7 hours showing narrower sulci than other durations. This effect remained significant after including subjective depression as a covariate, which also had a significant main effect on sulcal width in the model. There was no significant effect of napping on sulcal width. In path analyses where the effects of age, self-reported sleep duration and depression symptoms were investigated together, sulcal width mediated the relationship between age and cognition. We also observed a significant indirect effect of sulci width in the subjective depression-cognition relationship. Findings suggest that self-reported sleep duration and subjective depression may each be independently associated with brain morphology, which is related to cognitive functions. Results could help inform clinical trials and related intervention studies that aim at delaying cognitive decline in adults at risk of developing dementia.

The relationship between sleep duration and cortical sulcal width in midlife and older adults

AbstractBackgroundEmerging evidence suggests that poor sleep is associated with worse cognitive and structural brain health, and an increased risk of developing dementia (Bubu et al., 2016; Fjell et al., 2022; Tai et al., 2022). The present study investigated the influence of sleep duration on the cognition‐brain relationship in older adults using sulcal width (SW), a reliable measure of changes in the ageing brain (Bertoux et al., 2019). The influence of napping, depression likelihood, and genetic risk for dementia (APOE ε4 status) was also explored.MethodParticipants were 137 cognitively normal adults, aged 46‐72 from the Prospective Imaging Study of Ageing (PISA). Demographic information, sleep duration, and depressive symptoms were collected via online questionnaires. Cognition was assessed using the Cambridge Brain Systems battery. APOE genotype was determined from blood‐extracted DNA. Imaging data was acquired using a 3T Siemens PRISMA scanner. SW was extracted using the Morphologist pipeline (Borne et al., 2020).Canonical Partial Least Squares (PLS) were used to obtain latent variables of cognition and SW. ANCOVAs measured the effect of sleep duration categories (7‐7.5 hours versus {<7 or ≥8 hours}) on the cognitive and SW components, with sex and age as covariates. Status of depression likelihood was added as a covariate of interest. The effect of napping, and APOE ɛ4 allele on these same components were measured by ANCOVAs, with sex and age as covariates.ResultWe observed a significant effect of sleep duration on SW (F(1, 133) = 4.17, p = 0.043, Fig. 1). This effect remained significant (F(1,132) = 4.89, p = 0.029) after including depression likelihood as a covariate, which was also significant in the model (F(1,132) = 4.62, p = 0.034). A significant interaction between APOE ε4 status and age (p = 0.050) on SW was also observed.ConclusionResults add weight to studies suggesting that not too much or too little sleep is needed to maintain brain health in later life (Li et al., 2022; Liang et al., 2019). Depression, a risk factor for dementia (Livingston et al., 2020), was also associated with poorer brain health. Results suggest that at approximately 60 years of age, the influence of a positive APOE ε4 status is associated with increasing age‐related brain atrophy.

Can an online battery match in‐person cognitive testing in predicting age‐related cortical changes

AbstractBackgroundStudies into cognitive changes typically employ detailed in person cognitive testing, which is not always feasible. Therefore, we compared the relationship between brain morphology (sulcal width) and cognitive functioning, using an online and an in‐person modality and disentangled the influence of age, sex, β‐Amyloid (Aβ) and APOE‐status.Method141 healthy participants (mean age 60, range 46‐71 years, 75% female) assessed with structural MRI; cognitive batteries both, face‐to‐face and online (Cambridge Brain Systems), Aβ status (Fluorine‐18 florbetaben‐PET scan) and APOE genotype (Lupton et al., 2021); Canonical Partial Least Square method to compare cognitive modalities and Sulcal width (SW; Morphologist pipeline‐BrainVISA toolbox; Borne et al., 2020). Age effects tested with two‐sided Wald Test. Analysis of covariance to test age and sex‐interactions, amyloid and APOE status, sex‐effects (controlling for age), Aβ, and APOE (controlling for age and sex).ResultThe single robust mode for brain (SW) ‐ behaviour (cognition) covariation loaded most strongly onto memory and executive functions for both the onsite (1st mode, p = 0.013, cov = 3.55, z‐cov = 2.93, R2 = 0.18, z‐R2 = 0.95; 2nd mode, p>0.99), and the online battery (1st mode, p<0.001, cov = 2.76, z‐cov = 4.71, R2 = 0.14, z‐R2 = 1.15; 2nd mode, p = 0.99) (Fig. 1).Cognition‐related SW showed a regional pattern similar for online and in person cognitive appraisal. Significant effect of sex on SW projections in both the online and onsite conditions with larger sulcal width for men (p<0.001) and a similar effect on onsite cognitive projections with lower performance for men (p<0.001) (Fig. 2a). Cognitive performance ‐ both online (p = 0.03) and in‐person (p<0.01) – showed a significantly steeper decline with age for Aβ‐positive participants (Fig. 2b). Variance explained for the online cognitive assay (R2 = 0.15) was only slightly less than for the in‐person testing (R2 = 0.18). Brain‐behaviour z‐transformed covariance was likewise comparable across modalities.ConclusionSimilar sulcal width brain projections for both cognitive modalities, with memory and executive domains showing the strongest loadings. Aβ‐aggregation associated with a steeper cognitive projection slope for both batteries, suggesting that in our preclinical sample the early stages of Aβ accumulation accelerate cognitive ageing potentially before translation into structural brain changes. Adequate sensitivity of online cognitive tests for studying age‐related neurobiology of cognition is suggested.

Sulcal morphology as cognitive decline predictor in older adults with memory complaints

To determine whether sulcal morphology can predict changes in cognition, we investigated the relationship between width of 20 cerebral sulci and cognitive decline. Sulcal width was measured in T1-weighted MRI images at baseline in 433 adults aged ≥70 years with memory complaints from the MRI-Multidomain Alzheimer Preventive Trial study. Cognition was evaluated at baseline, 6, 12, 24, and 36 months of follow-up with a composite Z score. The composite score variations over time relative to the baseline sulcal width were assessed using linear mixed regression models. We observed a positive association between a greater decline in cognitive composite score and the width of the superior and the anterior inferior temporal sulci, and the cingulate anterior sulcus of the left hemisphere. Sulcal widening in the lateral temporal and the cingulate anterior areas might predict cognitive decline in individuals with memory complaints.

Sulcal characteristics patterns and gyrification gradient at different stages of Anorexia Nervosa: A structural MRI evaluation

Previous research evidenced alterations of different cortical parameters in patients with acute Anorexia Nervosa (AN), but no study to date investigated the morphology of individual sulci and their relationship with other structural indices. Our study aims at exploring the depth and width of 16 major cortical sulci in AN at different stages of the disorder and their relationships with the gyrification gradient. Two samples were included in the study. The first involved 38 patients with acute AN, 20 who fully recovered from AN, and 38 healthy women (HW); the second included 16 patients with AN and 16 HW. Sulcal width and depth were estimated for 16 sulci and outlined with a factorial analysis. An anterior-posterior gradient of gyrification was also extracted. Compared to HW, patients with acute AN displayed higher width and depth values in specific cortical sulci, and an altered gyrification gradient in areas encompassing the Central Sulcus, and Parieto-Temporal and Frontal Lobe regions. Sulcal width negatively correlated with gyrification gradient in areas where these values are altered in AN patients. Our results suggest the presence of alterations in sulcal morphology with a pattern similar to the gyrification gradient one and which seems to be related with malnutrition.

Sex Differences in Lifespan Trajectories and Variability of Human Sulcal and Gyral Morphology.

Sex differences in the development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, gyral span, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants 2 scans, 104 three scans, age range: 16-70years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. Although hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and lower variability for sulcal width. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.

Genome-wide haplotype association study in imaging genetics using whole-brain sulcal openings of 16,304 UK Biobank subjects

Neuroimaging-genetics cohorts gather two types of data: brain imaging and genetic data. They allow the discovery of associations between genetic variants and brain imaging features. They are invaluable resources to study the influence of genetics and environment in the brain features variance observed in normal and pathological populations. This study presents a genome-wide haplotype analysis for 123 brain sulcus opening value (a measure of sulcal width) across the whole brain that include 16,304 subjects from UK Biobank. Using genetic maps, we defined 119,548 blocks of low recombination rate distributed along the 22 autosomal chromosomes and analyzed 1,051,316 haplotypes. To test associations between haplotypes and complex traits, we designed three statistical approaches. Two of them use a model that includes all the haplotypes for a single block, while the last approach considers each haplotype independently. All the statistics produced were assessed as rigorously as possible. Thanks to the rich imaging dataset at hand, we used resampling techniques to assess False Positive Rate for each statistical approach in a genome-wide and brain-wide context. The results on real data show that genome-wide haplotype analyses are more sensitive than single-SNP approach and account for local complex Linkage Disequilibrium (LD) structure, which makes genome-wide haplotype analysis an interesting and statistically sound alternative to the single-SNP counterpart.

A slower rate of sulcal widening in the brains of the nondemented oldest old

The relationships between aging and brain morphology have been reported in many previous structural brain studies. However, the trajectories of successful brain aging in the extremely old remain underexplored. In the limited research on the oldest old, covering individuals aged 85 years and older, there are very few studies that have focused on the cortical morphology, especially cortical sulcal features. In this paper, we measured sulcal width and depth as well as cortical thickness from T1-weighted scans of 290 nondemented community-dwelling participants aged between 76 and 103 years. We divided the participants into young old (between 76 and 84; mean = 80.35±2.44; male/female = 76/88) and oldest old (between 85 and 103; mean = 91.74±5.11; male/female = 60/66) groups. The results showed that most of the examined sulci significantly widened with increased age and that the rates of sulcal widening were lower in the oldest old. The spatial pattern of the cortical thinning partly corresponded with that of sulcal widening. Compared to females, males had significantly wider sulci, especially in the oldest old. This study builds a foundation for future investigations of neurocognitive disorders and neurodegenerative diseases in the oldest old, including centenarians.

Morphological changes in the central sulcus of children with isolated growth hormone deficiency versus idiopathic short stature.

In this study, the morphological changes in the central sulcus between children with isolated growth hormone deficiency (IGHD) and those with idiopathic short stature (ISS) were analyzed. Thirty children with IGHD (peak growth hormone<5µg/L) and 30 children with ISS (peak growth hormone>10.0µg/L) were included. Morphological measurements of the central sulcus were obtained from T1-weighted MRIs using BrainVISA, including the average sulcal width, maximum depth, average depth, top length, bottom length, and depth position-based profiles (DPPs). The bilateral average width of the central sulci was significantly wider, while the left maximum depth and right average depth of the central sulcus were significantly smaller, in children with IGHD than in children with ISS. There were no significant differences in the right maximum depth, left average depth, or bilateral top length and bottom length of the central sulcus between groups. The DPPs of the middle part of both central sulci (corresponding to the hand motor activation area) and the inferior part of the right central sulcus (corresponding to the oral movement area) near the Sylvian fissure were significantly smaller in children with IGHD than in controls before false discovery rate (FDR) correction. However, all the above significant DPP sites disappeared after FDR correction. There were significant morphological changes in the three-dimensional structure of the central sulcus in children with IGHD, which were the outcome of other more essential cortical or subcortical changes, resulting in their relatively slower development in motor, cognitive, and linguistic functional performance.

Dissimilarity in Sulcal Width Patterns in the Cortex can be Used to Identify Patients With Schizophrenia With Extreme Deficits in Cognitive Performance.

Schizophrenia is a biologically complex disorder with multiple regional deficits in cortical brain morphology. In addition, interindividual heterogeneity of cortical morphological metrics is larger in patients with schizophrenia when compared to healthy controls. Exploiting interindividual differences in the severity of cortical morphological deficits in patients instead of focusing on group averages may aid in detecting biologically informed homogeneous subgroups. The person-based similarity index (PBSI) of brain morphology indexes an individual's morphometric similarity across numerous cortical regions amongst a sample of healthy subjects. We extended the PBSI such that it indexes the morphometric similarity of an independent individual (eg, a patient) with respect to healthy control subjects. By employing a normative modeling approach on longitudinal data, we determined an individual's degree of morphometric dissimilarity to the norm. We calculated the PBSI for sulcal width (PBSI-SW) in patients with schizophrenia and healthy control subjects (164 patients and 164 healthy controls; 656 magnetic resonance imaging scans) and associated it with cognitive performance and cortical sulcation index. A subgroup of patients with markedly deviant PBSI-SW showed extreme deficits in cognitive performance and cortical sulcation. Progressive reduction of PBSI-SW in the schizophrenia group relative to healthy controls was driven by these deviating individuals. By explicitly leveraging interindividual differences in the severity of PBSI-SW deficits, neuroimaging-driven subgrouping of patients is feasible. As such, our results pave the way for future applications of morphometric similarity indices for subtyping of clinical populations.

The reliability and heritability of cortical folds and their genetic correlations across hemispheres

Cortical folds help drive the parcellation of the human cortex into functionally specific regions. Variations in the length, depth, width, and surface area of these sulcal landmarks have been associated with disease, and may be genetically mediated. Before estimating the heritability of sulcal variation, the extent to which these metrics can be reliably extracted from in-vivo MRI must be established. Using four independent test-retest datasets, we found high reliability across the brain (intraclass correlation interquartile range: 0.65–0.85). Heritability estimates were derived for three family-based cohorts using variance components analysis and pooled (total N > 3000); the overall sulcal heritability pattern was correlated to that derived for a large population cohort (N > 9000) calculated using genomic complex trait analysis. Overall, sulcal width was the most heritable metric, and earlier forming sulci showed higher heritability. The inter-hemispheric genetic correlations were high, yet select sulci showed incomplete pleiotropy, suggesting hemisphere-specific genetic influences.

Novel multi-linear quantitative brain volume formula for manual radiological evaluation of brain atrophy

ObjectivesThe brain atrophy commonly occurs in elderly and in some childhood conditions making the techniques for quantifying brain volume needful. Since the automated quantitative methods of brain volume assessment have limited availability in developing countries, it was the purpose of this study to design and test an alternative formula that is applicable to all healthcare levels. MethodsThe multi-linear diagonal brain fraction formula (DBF) was designed from dimensions of brain relative to skull and ventricles. To test a developed formula, a total of 347 subjects aged between 0 and 18 years who had brain CT scans performed recruited and subjected to a systematic measurement of their brains in a diagonal brain fashion. ResultsOut of 347 patients evaluated, 62 subjects (17.8 %) were found to be cases of brain atrophy. The three radiological measurements which included sulcal width (SW), ventricular width (VW) and Evans Index (EI) were concurrently performed. SW and VW showed good age correlation. Similar tests were extended to diagonal brain fraction (DBF) and skull vertical horizontal ratio (VHR) in which DBF showed significant age correlation. ConclusionsThe DBF formula shows significant ability of differentiating changes of brain volume suggesting that it can be utilized as an alternative brain fraction quantification method bearing technical simplicity in assessing gross brain volume. Advances in knowledgeThe designed formula is unique in that it captures even the possible asymmetrical volume loss of brain through diagonal lines. The proposed scores being in term of ratios give four grades of brain atrophy.

Brain age prediction using deep learning uncovers associated sequence variants

Machine learning algorithms can be trained to estimate age from brain structural MRI. The difference between an individual’s predicted and chronological age, predicted age difference (PAD), is a phenotype of relevance to aging and brain disease. Here, we present a new deep learning approach to predict brain age from a T1-weighted MRI. The method was trained on a dataset of healthy Icelanders and tested on two datasets, IXI and UK Biobank, utilizing transfer learning to improve accuracy on new sites. A genome-wide association study (GWAS) of PAD in the UK Biobank data (discovery set: N=12378, replication set: N=4456) yielded two sequence variants, rs1452628-T (beta =-0.08, P=1.15times{10}^{-9}) and rs2435204-G (beta =0.102, P=9.73times 1{0}^{-12}). The former is near KCNK2 and correlates with reduced sulcal width, whereas the latter correlates with reduced white matter surface area and tags a well-known inversion at 17q21.31 (H2).

A novel voxel-based method to estimate cortical sulci width and its application to compare patients with Alzheimer’s disease to controls

A voxel-based method for measuring sulcal width was developed, validated and applied to a database. This method (EDT-based LM) employs the 3D Euclidean Distance Transform (EDT) of the pial surface and a Local Maxima labeling algorithm. A computational phantom was designed to test method performance; results revealed the method’s inaccuracy δ, to range between 0.1 and 0.5 voxels, for a width that varied between 1 and 7 voxels. Two morphological descriptors were computed to characterize each defined sulcus: mean sulcal width (MSW) and mean absolute deviation (MAD). The former is the average width for all available width measurements within the sulcus, and the latter is the deviation of these measurements. The EDT-based LM method was applied to the Minimal Interval Resonance Imaging in the Alzheimer’s Disease (MIRIAD) database, for a set of high-resolution Magnetic Resonance (MR) images of 66 subjects: 43 patients with Alzheimer Disease (AD) and 23 control subjects. AD causes significant gray matter loss; hence, some sulci were expected to broaden. Methodological results concurred with this hypothesis. After a Wilcoxon test, MSW was grater in the case of all sulci pertaining to AD patients, (p < 0.05, FDR corrected), whereas MAD showed significant differences in 8 sulci (p < 0.05, FDR corrected). This work presents a novel voxel-based method for measuring sulcal width and extracting descriptors to characterize and compare the sulci within and across subjects.

Sulcal morphology in Alzheimer's disease: an effective marker of diagnosis and cognition

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.

Robust estimation of sulcal morphology

While it is well established that cortical morphology differs in relation to a variety of inter-individual factors, it is often characterized using estimates of volume, thickness, surface area, or gyrification. Here we developed a computational approach for estimating sulcal width and depth that relies on cortical surface reconstructions output by FreeSurfer. While other approaches for estimating sulcal morphology exist, studies often require the use of multiple brain morphology programs that have been shown to differ in their approaches to localize sulcal landmarks, yielding morphological estimates based on inconsistent boundaries. To demonstrate the approach, sulcal morphology was estimated in three large sample of adults across the lifespan, in relation to aging. A fourth sample is additionally used to estimate test–retest reliability of the approach. This toolbox is now made freely available as supplemental to this paper: https://cmadan.github.io/calcSulc/.

Pregnancy and adolescence entail similar neuroanatomical adaptations: A comparative analysis of cerebral morphometric changes

Mapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long-lasting reduction in cerebral gray matter volume. However, the morphometric features behind the volumetric reductions remain unexplored. Furthermore, the similarity between these reductions and those occurring during adolescence, another hormonally similar transitional period of life, still needs to be investigated. Here, we used surface-based methods to analyze the longitudinal magnetic resonance imaging data of a group of 25 first-time mothers (before and after pregnancy) and compare them to those of a group of 25 female adolescents (during 2 years of pubertal development). For both first-time mothers and adolescent girls, a monthly rate of volumetric reductions of 0.09 mm3 was observed. In both cases, these reductions were accompanied by decreases in cortical thickness, surface area, local gyrification index, sulcal depth, and sulcal length, as well as increases in sulcal width. In fact, the changes associated with pregnancy did not differ from those that characterize the transition during adolescence in any of these measures. Our findings are consistent with the notion that the brain morphometric changes associated with pregnancy and adolescence reflect similar hormonally primed biological processes.

Relationship Between Sulcal Characteristics and Brain Aging.

This study aimed to determine whether sulcal morphology differs between middle age (MA) and older healthy individuals. Furthermore, we sought to determine whether age-related differences in sulcal characteristics were more strongly associated with differences in local or global cortical volumes. Participants (age 44–50, N = 403; age 64–70, N = 390) from the Personality and Total Health Through Life (PATH) study were included. Sulci were 17.3% wider, on average, in old age (OA) compared to MA participants, with the largest difference in the left superior frontal sulcus. Differences in sulcal width were generally higher in males than females. Differences in the width of the superior frontal and central sulci were significantly associated with differences in the volume of adjacent local gyri, while age-related differences in the width of lateral and superior temporal sulci were associated with differences in whole brain cortical volume. These findings suggest that sulcal characteristics provide unique information about changes in local and global brain structure in aging.

Identification of Early-Stage Alzheimer's Disease Using Sulcal Morphology and Other Common Neuroimaging Indices.

Identifying Alzheimer’s disease (AD) at its early stage is of major interest in AD research. Previous studies have suggested that abnormalities in regional sulcal width and global sulcal index (g-SI) are characteristics of patients with early-stage AD. In this study, we investigated sulcal width and three other common neuroimaging morphological measures (cortical thickness, cortical volume, and subcortical volume) to identify early-stage AD. These measures were evaluated in 150 participants, including 75 normal controls (NC) and 75 patients with early-stage AD. The global sulcal index (g-SI) and the width of five individual sulci (the superior frontal, intra-parietal, superior temporal, central, and Sylvian fissure) were extracted from 3D T1-weighted images. The discriminative performances of the other three traditional neuroimaging morphological measures were also examined. Information Gain (IG) was used to select a subset of features to provide significant information for separating NC and early-stage AD subjects. Based on the four modalities of the individual measures, i.e., sulcal measures, cortical thickness, cortical volume, subcortical volume, and combinations of these individual measures, three types of classifiers (Naïve Bayes, Logistic Regression and Support Vector Machine) were applied to compare the classification performances. We observed that sulcal measures were either superior than or equal to the other measures used for classification. Specifically, the g-SI and the width of the Sylvian fissure were two of the most sensitive sulcal measures and could be useful neuroanatomical markers for detecting early-stage AD. There were no significant differences between the three classifiers that we tested when using the same neuroanatomical features.