Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease.

Mild cognitive impairment can represent a transitional state between normal ageing and Alzheimer's disease. Non-invasive diagnostic methods are needed to identify mild cognitive impairment individuals for early therapeutic interventions. Our objective was to determine whether automated magnetic resonance imaging-based measures could identify mild cognitive impairment individuals with a high degree of accuracy. Baseline volumetric T1-weighted magnetic resonance imaging scans of 313 individuals from two independent cohorts were examined using automated software tools to identify the volume and mean thickness of 34 neuroanatomic regions. The first cohort included 49 older controls and 48 individuals with mild cognitive impairment, while the second cohort included 94 older controls and 57 mild cognitive impairment individuals. Sixty-five patients with probable Alzheimer's disease were also included for comparison. For the discrimination of mild cognitive impairment, entorhinal cortex thickness, hippocampal volume and supramarginal gyrus thickness demonstrated an area under the curve of 0.91 (specificity 94%, sensitivity 74%, positive likelihood ratio 12.12, negative likelihood ratio 0.29) for the first cohort and an area under the curve of 0.95 (specificity 91%, sensitivity 90%, positive likelihood ratio 10.0, negative likelihood ratio 0.11) for the second cohort. For the discrimination of Alzheimer's disease, these three measures demonstrated an area under the curve of 1.0. The three magnetic resonance imaging measures demonstrated significant correlations with clinical and neuropsychological assessments as well as with cerebrospinal fluid levels of tau, hyperphosphorylated tau and abeta 42 proteins. These results demonstrate that automated magnetic resonance imaging measures can serve as an in vivo surrogate for disease severity, underlying neuropathology and as a non-invasive diagnostic method for mild cognitive impairment and Alzheimer's disease

Regionally specific TSC1 and TSC2 gene expression in tuberous sclerosis complex

Tuberous sclerosis complex (TSC), a heritable neurodevelopmental disorder, is caused by mutations in the TSC1 or TSC2 genes. To date, there has been little work to elucidate regional TSC1 and TSC2 gene expression within the human brain, how it changes with age, and how it may influence disease. Using a publicly available microarray dataset, we found that TSC1 and TSC2 gene expression was highest within the adult neo-cerebellum and that this pattern of increased cerebellar expression was maintained throughout postnatal development. During mid-gestational fetal development, however, TSC1 and TSC2 expression was highest in the cortical plate. Using a bioinformatics approach to explore protein and genetic interactions, we confirmed extensive connections between TSC1/TSC2 and the other genes that comprise the mammalian target of rapamycin (mTOR) pathway, and show that the mTOR pathway genes with the highest connectivity are also selectively expressed within the cerebellum. Finally, compared to age-matched controls, we found increased cerebellar volumes in pediatric TSC patients without current exposure to antiepileptic drugs. Considered together, these findings suggest that the cerebellum may play a central role in TSC pathogenesis and may contribute to the cognitive impairment, including the high incidence of autism spectrum disorder, observed in the TSC population

Correlation results between cortical thickness of eight neocortical ROIs and total hippocampal volume in only CN individuals (n = 208).

<p>Spearman's rank correlation coefficients listed with p-values in parentheses. All analyses included age, gender, education, and APOE-ε4 carrier status as co-variates. HV = Hippocampal volume, CMF = Caudal portion of middle frontal gyrus thickness, ERC = Entorhinal cortex thickness, IPL = Inferior parietal lobule thickness, ITG = Inferior temporal gyrus thickness, ISC = Isthmus portion of cingulate cortex thickness, LOC = Lateral portion of occipital cortex thickness, MOF = Medial portion of orbital frontal cortex thickness, TPC = Temporal pole thickness, NS = Not significant.</p

Three-dimensional representations of the 8 ROIs examined in the current study (only right hemisphere is shown).

<p>All of the ROIs visible in the lateral (top) and medial (bottom) views of the gray matter surface.</p

Descriptive statistical information for the participants in the study (means listed with standard deviations in parentheses).

<p>Descriptive statistical information for the participants in the study (means listed with standard deviations in parentheses).</p

Correlation results between cortical thickness of eight neocortical ROIs and total hippocampal volume in only AD individuals (n = 163).

<p>Spearman's rank correlation coefficients listed with p-values in parentheses. All analyses included age, gender, education, and APOE-ε4 carrier status as co-variates. HV = Hippocampal volume, CMF = Caudal portion of middle frontal gyrus thickness, ERC = Entorhinal cortex thickness, IPL = Inferior parietal lobule thickness, ITG = Inferior temporal gyrus thickness, ISC = Isthmus portion of cingulate cortex thickness, LOC = Lateral portion of occipital cortex thickness, MOF = Medial portion of orbital frontal cortex thickness, TPC = Temporal pole thickness, NS = Not significant.</p

Correlation results between cortical thickness of eight neocortical ROIs and total hippocampal volume in all ADNI participants (n = 724).

<p>Spearman's rank correlation coefficients listed, all p-values significant at <0.0001. All analyses included age, gender, education, and APOE-ε4 carrier status as co-variates. HV = Hippocampal volume, CMF = Caudal portion of middle frontal gyrus thickness, ERC = Entorhinal cortex thickness, IPL = Inferior parietal lobule thickness, ITG = Inferior temporal gyrus thickness, ISC = Isthmus portion of cingulate cortex thickness, LOC = Lateral portion of occipital cortex thickness, MOF = Medial portion of orbital frontal cortex thickness, TP = Temporal pole thickness.</p

General linear model analyses demonstrating the prediction of longitudinal hippocampal atrophy (over one year) using baseline cortical thickness for the amyloid positive (top panel) and p-tau positive individuals (bottom panel).

<p>All results are corrected for multiple comparisons by method of Monte Carlo simulation and shown on the gray matter surface (only right hemisphere). The color scale illustrates the magnitude of effect with blue indicating areas of strongest prediction strength.</p