Subcortical Gray Matter Atrophy Research Articles

Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis

Background: The effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear. Objective: To determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS. Methods: A non-randomized, observational cohort of people with MS followed with annual brain magnetic resonance imaging (MRI) was evaluated retrospectively. Whole brain, subcortical gray matter (GM), cortical GM, and cerebral white matter (WM) volume fractions were obtained. DMTs were categorized as higher (DMT-H: natalizumab and rituximab) or lower (DMT-L: interferon-beta and glatiramer acetate) efficacy. Follow-up epochs were analyzed if participants had been on a DMT for ⩾6 months prior to baseline and had at least one follow-up MRI while on DMTs in the same category. Results: A total of 86 DMT epochs (DMT-H: n = 32; DMT-L: n = 54) from 78 participants fulfilled the study inclusion criteria. Mean follow-up was 2.4 years. Annualized rates of thalamic (−0.15% vs −0.81%; p = 0.001) and putaminal (−0.27% vs −0.73%; p = 0.001) atrophy were slower during DMT-H compared to DMT-L epochs. These results remained significant in multivariate analyses including demographics, clinical characteristics, and T2 lesion volume. Conclusion: DMT-H treatment may be associated with slower rates of subcortical GM atrophy, especially of the thalamus and putamen. Thalamic and putaminal volumes are promising imaging biomarkers in MS.

Atrophic brain signatures of mild forms of neurocognitive impairment in virally suppressed HIV infection.

There is a lack of evidence for the neurobiological underpinning of asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorders (MNDs) in virally suppressed HIV-positive persons. We hypothesized that such mild impairment would be associated with focal brain atrophy. A cross-sectional observational study. Eighty-five virally suppressed HIV-positive and 44 geographically, demographically and lifestyle comparable HIV-negative men underwent anatomical MRI, neuropsychological evaluation and HIV laboratory tests. Volumes of interest (VOI) from magnetic resonance (MR) images were extracted using FreeSurfer to yield grey and white matter volumes in regions associated with HIV-related brain injury. HIV-associated neurocognitive disorder (HAND) [ANI = 38%, MND = 13%, HIV-associated dementia (HAD) = 3% vs. neuropsychologically-normal] was classified using Global Deficit Score (GDS ≥0.5) and functional decline. Effects of HIV status on VOI were assessed with multivariate analyses controlling for family-wise error. HAND categories and HIV biomarker effects on VOI were assessed with multiple regression. Relative to the HIV-negative group, the HIV-positive group demonstrated subcortical grey (d = 0.50-0.60) and white matter (d = 0.43-0.69) atrophy, with relative cortical sparing (d = 0.23). ANI showed reduced medial-orbitofrontal white matter compared with NP-normal cases (P = 0.04). MND showed enlarged lateral ventricles (P = 0.02) and reduced caudal-middle-frontal white matter (P = 0.04), caudal-anterior-cingulate white matter (P = 0.006) and inferior-parietal white matter (P = 0.04) compared with neuropsychologically normal. Across the HIV-positive group, lower CD4+/CD8 ratio was the strongest predictor of atrophy in subcortical regions. Across HAND categories, HIV disease duration uniquely predicted greater medial-orbitofrontal white matter atrophy only in ANI (P = 0.002). ANI shows specific frontal white matter atrophy to which HIV disease duration is a unique contributor. MND is characterized by more widespread subcortical atrophy.

Brainstem atrophy in focal epilepsy destabilizes brainstem-brain interactions: Preliminary findings

BackgroundMR Imaging has shown atrophy in brainstem regions that were linked to autonomic dysfunction in epilepsy patients. The brainstem projects to and modulates the activation state of several wide-spread cortical/subcortical regions. The goal was to investigate 1. Impact of brainstem atrophy on gray matter connectivity of cortical/subcortical structures and autonomic control. 2. Impact on the modulation of cortical/subcortical functional connectivity.Methods11 controls and 18 patients with non-lesional focal epilepsy (FE) underwent heart rate variability (HRV) measurements and a 3 T MRI (T1 in all subjects, task-free fMRI in 7 controls/ 12 FE). The brainstem was extracted, and atrophy assessed using deformation-based-morphometry. The age-corrected z-scores of the mean Jacobian determinants were extracted from 71 5x5x5 mm grids placed in brainstem regions associated with autonomic function. Cortical and non-brainstem subcortical gray matter atrophy was assessed with voxel-based-morphometry and mean age corrected z-scores of the modulated gray matter volumes extracted from 380 cortical/subcortical rois. The profile similarity index was used to characterize the impact of brainstem atrophy on gray matter connectivity. The fMRI was preprocessed in SPM12/Conn17 and the BOLD signal extracted from 398 ROIs (16 brainstem). A dynamic task-free analysis approach was used to identify activation states. Connectivity HRV relationship were assessed with Spearman rank correlations.ResultsHRV was negatively correlated with reduced brainstem right hippocampus/parahippocampus gray matter connectivity in controls (p < .05, FDR) and reduced brainstem to right parietal cortex, lingual gyrus, left hippocampus/amygdala, parahippocampus, temporal pole, and bilateral anterior thalamus connectivity in FE (p < .05, FDR). Dynamic task-free fMRI analysis identified 22 states. The strength of the functional brainstem/cortical connectivity of state 15 was negatively associated with HRV (r = −0.5, p = .03) and positively with decreased brainstem-cortical (0.49, p = .03) gray matter connectivity.ConclusionThe findings of this small pilot study suggest that impaired brainstem-cortex gray matter connectivity in FE negatively affects the brainstem's ability to control cortical activation.

The width of the third ventricle associates with cognition and behaviour in motor neuron disease.

An enlarged width of the third ventricle (WTV) has been described in amyotrophic lateral sclerosis (ALS) patients, although its clinical meaning is unknown. The aims of this study were to evaluate the contribution of demographical, clinical and genetic factors to the WTV in different motor neuron disease (MND) phenotypes and to assess its brain structural correlates. The WTV was measured by transcranial ultrasound in 107 MND patients (82 diagnosed with classical ALS, 16 with progressive muscular atrophy and 9 with primary lateral sclerosis) and 25 controls. Genetic analysis, and neurological and neuropsychological examinations were performed in patients. Brain volumetric analysis of MR images was obtained in 85 patients. The association of WTV with demographical, clinical, genetic and neuropsychological variables as well as with brain volumes was assessed by multivariable models. Eighteen patients were diagnosed with genetic MND and 42.3% of patients showed executive or behavioural impairment (EBI). MND patients showed larger WTV than controls. The WTV was significantly associated with age, spinal onset and the presence of EBI, but not with the genetic background, the phenotype or disability. Greater WTV was also associated with reduced subcortical grey matter volume, but not with the cortical or the white matter volume. The enlargement of the WTV found in the different MND phenotypes is attributable to the subcortical grey matter atrophy and is associated with cognitive and behavioural impairment. Larger longitudinal studies are needed to determine its role as biomarker in MND patients with frontotemporal dementia.

Impact of Focal White Matter Damage on Localized Subcortical Gray Matter Atrophy in Multiple Sclerosis: A 5-Year Study.

It is unclear to what extent subcortical gray matter atrophy is a primary process as opposed to a result of focal white matter damage. Correlations between WM damage and atrophy of subcortical gray matter have been observed but may be partly attributable to indirect relationships between co-occurring processes arising from a common cause. Our aim was to cross-sectionally and longitudinally characterize the unique impact of focal WM damage on the atrophy of connected subcortical gray matter regions, beyond what is explainable by global disease progression. One hundred seventy-six individuals with MS and 47 healthy controls underwent MR imaging at baseline and 5 years later. Atrophy and lesion-based disruption of connected WM tracts were evaluated for 14 subcortical gray matter regions. Hierarchic regressions were applied, predicting regional atrophy from focal WM disruption, controlling for age, sex, disease duration, whole-brain volume, and T2-lesion volume. When we controlled for whole-brain volume and T2-lesion volume, WM tract disruption explained little additional variance of subcortical gray matter atrophy and was a significant predictor for only 3 of 14 regions cross-sectionally (ΔR2 = 0.004) and 5 regions longitudinally (ΔR2 = 0.016). WM tract disruption was a significant predictor for even fewer regions when correcting for multiple comparisons. WM tract disruption accounts for a small percentage of atrophy in connected subcortical gray matter when controlling for overall disease burden and is not the primary driver in most cases.

Imaging patterns of gray and white matter abnormalities associated with PASAT and SDMT performance in relapsing-remitting multiple sclerosis

Objectives: To map the regional patterns of white matter (WM) microstructural abnormalities and gray matter (GM) atrophy exclusively associated with reduced performance in the Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT) in relapsing-remitting (RR) multiple sclerosis (MS) patients. Methods: In all, 177 RRMS patients and 80 healthy controls (HC) were studied. WM microstructural abnormalities were investigated on diffusion tensor images using tract-based spatial statistics analysis, and regional GM atrophy was estimated on three-dimensional (3D) T1-weighted images using voxel-based morphometry. Results: Compared to HC, RRMS patients showed the expected pattern of cortical–subcortical GM atrophy and WM microstructural abnormalities. In patients, diffusivity abnormalities of supratentorial WM tracts correlated with both SDMT and PASAT scores. Lower SDMT performance was also associated with WM damage in several infratentorial WM tracts. Lower SDMT scores correlated with atrophy of the right anterior cingulate cortex, left postcentral gyrus, and right middle temporal gyrus, whereas lower PASAT scores correlated with atrophy of the deep GM nuclei, bilaterally, and several fronto-temporo-occipital regions. Conclusion: In RRMS patients, regional damage of different neural systems helps explaining reduced performance in SDMT and PASAT. WM microstructural damage typified reduced SDMT performance, whereas atrophy of several GM regions distinguished reduced PASAT performance.

Brain volumetric analysis and cortical thickness in adults with saccadic intrusions (ocular flutter or opsoclonus-myoclonus syndrome)

ObjectivesOcular flutter (OF) and opsoclonus are considered a continuum with a similar pathogenesis. Due to the rarity of this disease in the adult population, little is known about the brain morphological changes in the chronic phase of the disease. Patients and methodsSix magnetic resonance imaging from adults with previous history of OF/Opsoclonus and 12 healthy patients (paired by age and sex) were analyzed in order to identify the long term cortical thickness pattern in this rare disease by using Freesurfer. ResultsPatients with OF/Opsoclonus showed reduced cerebellum cortical volume with a subsequent diminution in total cerebellar volume. White mater cerebellum volume was not modified. In addition, we have also identified a significant supratentorial gray matter volume decrease in OF/Opsoclonus patients, involving both the cortical and the subcortical gray matter. ConclusionsOF/Opsoclonus in adults may be associated with cortical and subcortical gray matter atrophy, as well as decreased cerebellar cortical volume. Further larger prospective studies are necessary to confirm these results.

High conscientiousness is related to less thalamic and other subcortical gray matter atrophy in multiple sclerosis (P4.343)

High conscientiousness is related to less thalamic and other subcortical gray matter atrophy in multiple sclerosis (P4.343)

Subcortical gray matter atrophy is predicted by white matter lesions in directly connected tracts in multiple sclerosis (P4.364)

Subcortical gray matter atrophy is predicted by white matter lesions in directly connected tracts in multiple sclerosis (P4.364)

Gray matter trophism, cognitive impairment, and depression in patients with multiple sclerosis

Background: Cognitive impairment and depression frequently affects patients with multiple sclerosis (MS). However, the relationship between the occurrence of depression and cognitive impairment and the development of cortical atrophy has not been fully elucidated yet. Objectives: To investigate the association of cortical and deep gray matter (GM) volume with depression and cognitive impairment in MS. Methods: Three-dimensional (3D) T1-weighted scans were obtained from 126 MS patients and 59 matched healthy controls. Cognitive impairment was assessed using the Brief Repeatable Battery of Neuropsychological Tests and depression with the Montgomery-Asberg Depression Rating Scale (MADRS). Using FreeSurfer and FIRST software, we assessed cortical thickness (CTh) and deep GM volumetry. Magnetic resonance imaging (MRI) variables explaining depression and cognitive impairment were investigated using factorial and classification analysis. Multivariate regression models correlated GM abnormalities with symptoms severity. Results: Compared with controls, MS patients exhibited widespread bilateral cortical thinning involving all brain lobes. Depressed MS showed selective CTh decrease in fronto-temporal regions, whereas cognitive impairment MS exhibited widespread fronto-parietal cortical and subcortical GM atrophy. Frontal cortical thinning was the best predictor of depression (C-statistic = 0.7), whereas thinning of the right precuneus and high T2 lesion volume best predicted cognitive impairment (C-statistic = 0.8). MADRS severity correlated with right entorhinal cortex thinning, whereas cognitive impairment severity correlated with left entorhinal and thalamus atrophy. Conclusion: MS-related depression is linked to circumscribed CTh changes in areas deputed to emotional behavior, whereas cognitive impairment is correlated with cortical and subcortical GM atrophy of circuits involved in cognition.

Grey matter abnormalities in methcathinone abusers with a Parkinsonian syndrome.

BackgroundA permanent Parkinsonian syndrome occurs in intravenous abusers of the designer psychostimulant methcathinone (ephedrone). It is attributed to deposition of contaminant manganese, as reflected by characteristic globus pallidus hyperintensity on T1‐weighted MRI.MethodsWe have investigated brain structure and function in methcathinone abusers (n = 12) compared to matched control subjects (n = 12) using T1‐weighted structural and resting‐state functional MRI.ResultsSegmentation analysis revealed significant (p < .05) subcortical grey matter atrophy in methcathinone abusers within putamen and thalamus bilaterally, and the left caudate nucleus. The volume of the caudate nuclei correlated inversely with duration of methcathinone abuse. Voxel‐based morphometry showed patients to have significant grey matter loss (p < .05) bilaterally in the putamina and caudate nucleus. Surface‐based analysis demonstrated nine clusters of cerebral cortical thinning in methcathinone abusers, with relative sparing of prefrontal, parieto‐occipital, and temporal regions. Resting‐state functional MRI analysis showed increased functional connectivity within the motor network of patients (p < .05), particularly within the right primary motor cortex.ConclusionTaken together, these results suggest that the manganese exposure associated with prolonged methcathinone abuse results in widespread structural and functional changes affecting both subcortical and cortical grey matter and their connections. Underlying the distinctive movement disorder caused by methcathinone abuse, there is a more widespread pattern of brain involvement than is evident from the hyperintensity restricted to the basal ganglia as shown by T1‐weighted structural MRI.

The selective anatomical vulnerability of ALS: ‘disease-defining’ and ‘disease-defying’ brain regions

A large multiparametric MRI study has been undertaken to evaluate anatomical patterns of basal ganglia, white matter and cortical grey matter involvement in ALS. Unaffected brain regions are mapped in patients with significant disability. Multiple white matter diffusivity measures, cortical grey matter density alterations, basal ganglia volumes and subcortical grey matter atrophy patterns are evaluated. Results demonstrated a strikingly selective anatomical vulnerability pattern in ALS that preferentially affects specific grey matter structures, commissural white matter tracts and basal ganglia regions, suggestive of networkwise neurodegeneration in ALS. In conclusion, ALS pathology exhibits predilection for selective and inter-connected anatomical sites that can be comprehensively characterized in vivo by multiparametric neuroimaging. The systematic characterization of unaffected brain regions in ALS has implications for the development of classifier analyses and elucidation of disease biology. The involvement and sparing of contiguous brain regions raises important pathophysiological, phylogenetic and ontogenetic questions regarding ALS pathogenesis and disease spread.

The pattern of gray matter atrophy in Parkinson's disease differs in cortical and subcortical regions.

Cortical and subcortical gray matter (GM) atrophy may progress differently during the course of Parkinson's disease (PD). We delineated and compared the longitudinal pattern of these PD-related changes. Structural MRIs and clinical measures were obtained from 76 PD with different disease durations and 70 Controls at baseline, 18-, and 36 months. Both cortical and subcortical (putamen, caudate, and globus pallidus) GM volumes were obtained, compared, and associated with PD clinical measures at baseline. Their volumes and rates of change also were compared among Controls, PDs, and PD subgroups based on duration of illness [≤1 year (PD(E)), 1-5 years (PD(M)), and >5 years (PD(L))]. Compared to Controls, PD subjects displayed smaller cortical GM and striatal(putamen, caudate, ps ≤0.001), volumes at baseline. Cortical GM volumes were negatively associated with disease duration at baseline, whereas striatal volumes were not. PD subjects demonstrated accelerated volume loss in cortical GM (p = 0.006), putamen (p = 0.034), and caudate (p = 0.008) compared to Controls. Subgroup analyses demonstrated that accelerated cortical atrophy reached statistical significance in PD subjects with duration of illness 1-5 years (PD(M), ps<0.001) and the trend of accelerated atrophy seemed to persist until later stages, whereas striatal atrophy occurred in PD subjects with PD(E) (p = 0.021 for putamen, p = 0.005 for caudate) and PD(M) (p = 0.002 for putamen, p = 0.001 for caudate) that significantly slowed down in PD(L) (ps for PD(L) vs PD(E) or PD(M): <0.01). The pattern of GM loss in PD differs in cortical and subcortical regions, with striatal atrophy occurring earlier and extra-striatal cortical atrophy later.

Subcortical Atrophy in Cognitive Impairment and Dementia.

Cortical atrophy is a key neuroimaging feature of dementia. However, the role of subcortical gray matter reduction in cognitive impairment has not been explored extensively. We examined the risk factors of subcortical structures on neuroimaging and their association with cognitive impairment and dementia. Data from two studies were used: a subsample from the Epidemiology of Dementia in Singapore (EDIS) study of non-demented community-dwelling subjects (n = 550) and a case-control study. Subjects underwent similar neuropsychological tests and brain MRI. Subcortical volumes of accumbens, amygdala, caudate, pallidum, putamen, thalamus, hippocampus, and brainstem were measured. Cognitive impairment no dementia (CIND), dementia and its subtypes, vascular cognitive impairment (VCI), were defined using accepted criteria. Cognitive function was also expressed as both composite and domain-specific Z-scores. In the EDIS study, age, female gender, Malay ethnicity, diabetes, lacunar-infarcts, and white matter lesions were the most important risk factors for subcortical atrophy. Moreover, smaller volumes of accumbens, amygdala, caudate, thalamus, and brainstem were significantly associated with lower cognitive composite Z-scores. With respect to clinical outcomes in the case-control study, structures such as the accumbens, caudate, putamen, and hippocampus were associated with both CIND and dementia. Smaller caudate and pallidum volumes were related to VCI whereas amygdalar atrophy was only associated with non-VCI. Furthermore, subcortical atrophy was related to both VCI and non-VCI. Subcortical gray matter atrophy is not only observed in dementia, but also in the preclinical stages of cognitive impairment. Furthermore, besides VCI, subcortical structures were also related to non-VCI.

Comparison of regional brain atrophy and cognitive impairment between pure akinesia with gait freezing and Richardson's syndrome

Pure akinesia with gait freezing (PAGF) is considered a clinical phenotype of progressive supranuclear palsy. The brain atrophy and cognitive deficits in PAGF are expected to be less prominent than in classical Richardson's syndrome (RS), but this hypothesis has not been explored yet. We reviewed the medical records of 28 patients with probable RS, 19 with PAGF, and 29 healthy controls, and compared cortical thickness, subcortical gray matter volume, and neuropsychological performance among the three groups. Patients with PAGF had thinner cortices in frontal, inferior parietal, and temporal areas compared with controls; however, areas of cortical thinning in PAGF patients were less extensive than those in RS patients. In PAGF patients, hippocampal, and thalamic volumes were also smaller than controls, whereas subcortical gray matter volumes in PAGF and RS patients were comparable. In a comparison of neuropsychological tests, PAGF patients had better cognitive performance in executive function, visual memory, and visuospatial function than RS patients had. These results demonstrate that cognitive impairment, cortical thinning, and subcortical gray matter atrophy in PAGF patients resemble to those in RS patients, though the severity of cortical thinning and cognitive dysfunction is milder. Our results suggest that, PAGF and RS may share same pathology but that it appears to affect a smaller proportion of the cortex in PAGF.

A Longitudinal Study of Disability, Cognition and Gray Matter Atrophy in Early Multiple Sclerosis Patients According to Evidence of Disease Activity.

New treatment options may make “no evidence of disease activity” (NEDA: no relapses or disability progression and no new/enlarging MRI lesions, as opposed to “evidence of disease activity” (EDA) with at least one of the former), an achievable goal in relapsing-remitting multiple sclerosis (RRMS). The objective of the present study was to determine whether early RRMS patients with EDA at one-year follow-up had different disability, cognition, treatment and gray matter (GM) atrophy rates from NEDA patients and healthy controls (HC). RRMS patients (mean age 34 years, mean disease duration 2.2 years) were examined at baseline and one-year follow-up with neurological (n = 72), neuropsychological (n = 56) and structural MRI (n = 57) examinations. Matched HC (n = 61) were retested after three years. EDA was found in 46% of RRMS patients at follow-up. EDA patients used more first line and less second line disease modifying treatment than NEDA (p = 0.004). While the patients groups had similar disability levels at baseline, they differed in disability at follow-up (p = 0.010); EDA patients progressed (EDSS: 1.8–2.2, p = 0.010), while NEDA patients improved (EDSS: 2.0–1.7, p<0.001). Cognitive function was stable in both patient groups. Subcortical GM atrophy rates were higher in EDA patients than HC (p<0.001). These results support the relevance of NEDA as outcome in RRMS and indicate that pathological neurodegeneration in RRMS mainly occur in patients with evidence of disease activity.

Atrophy of reward-related striatal structures in fatigued MS patients is independent of physical disability

Background: MRI studies have shown gray-matter abnormalities in fatigued multiple sclerosis (MS) patients. However, given that physical disability is highly correlated to MS fatigue, it is often difficult to disentangle its effect in these MRI findings. Objective: The objective of this research paper is to investigate gray-matter damage in mildly disabled MS patients, addressing which variables were better related to fatigue while controlling for physical disability and depression. Methods: Forty-nine relapsing–remitting MS (RRMS) patients and 30 controls underwent MRI (3T). Fatigue was assessed using the Fatigue Severity Scale (FSS). Multivariate logistic regression was performed to assess the contribution of clinical and MRI metrics to fatigue. Statistical analyses were performed controlling for disability and depression. Results: Fatigue was present in 22 (44.9%) patients. FSS score was highly correlated with EDSS (p = 0.00001). Patients with fatigue had lower brain cortical and subcortical gray-matter volumes. However, after controlling for EDSS, only the caudate and the accumbens volumes remained statistically significant. Conclusions: Fatigued MS patients have a global cortical and subcortical gray-matter atrophy that seems largely related to higher physical disability. However, striatal structures involved in effort-reward functions exhibited smaller volumes in fatigued patients, independently of physical disability and depressive symptoms, supporting the theory of cortico-striatal network impairment in MS fatigue.

Cognitive reserve moderates the impact of subcortical gray matter atrophy on neuropsychological status in multiple sclerosis

Background: Cognitive decline is characterized in multiple sclerosis (MS), but the rate and severity vary. The reserve hypothesis proposes that baseline neurological differences impact cognitive outcome in neurodegenerative disease. Objective: To elucidate how brain reserve and cognitive reserve influence subcortical gray matter (SCGM) atrophy and cognitive decline in MS over 3 years. Methods: Seventy-one MS patients and 23 normal controls underwent magnetic resonance imaging and cognitive assessment at baseline and 3-year follow-up. The influence of reserve on cognitive processing speed (CPS) and memory was examined. Results: SCGM volume and cognitive scores were lower in MS than normal controls (P⩽0.001). Accounting for baseline, comparison of follow-up means yielded a difference between groups in SCGM volume (P<0.001) but not cognition (NS). Cognitive reserve (P=0.005), but not brain reserve, contributed to CPS, with only low cognitive reserve MS subjects showing decline in CPS (P=0.029). SCGM change predicted CPS outcome in MS with low cognitive reserve (P=0.002) but not high cognitive reserve. There were no effects in the domain of memory. Conclusions: SCGM atrophy occurs in normal controls, but significantly more so in MS. While CPS did not change in normal controls, low cognitive reserve was associated with CPS decline in MS. High cognitive reserve protect MS patients from cognitive decline related to SCGM atrophy.

Relation between subcortical grey matter atrophy and conversion from mild cognitive impairment to Alzheimer's disease

ObjectiveTo investigate whether subcortical grey matter atrophy predicts progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD), and to compare subcortical volumes between AD, MCI and controls. To assess...

Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study.

We investigated the ability of cortical and subcortical gray matter (GM) atrophy in combination with white matter (WM) integrity to distinguish behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA) and higher mean (MD), axial (L1) and radial diffusivity (L23) values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97–100% of controls, 81–100% of AD and 67–75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD.