To demonstrate the feasibility of three-dimensional echo-planar spectroscopic imaging (EPSI) at short echo time (13 msec) with a conventional clinical imager in the human brain.
Periodic inversions ...of a readout gradient were used during data acquisition to simultaneously encode chemical shift and one spatial dimension in one excitation. Aliasing artifacts were avoided with a modified acquisition-and-processing method based on oversampling. A double outer-volume suppression technique that adapts to the ovoid brain shape was used to strongly reduce extracranial lipid resonances.
Three-dimensional spatial encoding in vivo of eight sections with 32 x 32 voxels each (0.75 cm3) was performed in 34 minutes with four signal averages. The spectral resolution and signal-to-noise ratio (S/N) of resonances of inositol, choline, creatine, glutamate and glutamine, and N-acetyl aspartate were consistent with those previously recorded with conventional phase encoding.
EPSI substantially reduces acquisition time for three-dimensional spatial encoding and yields a spectral quality similar to that obtained with conventional techniques without affecting the S/N per unit time and unit volume.
There is inconsistent evidence of the presence and direction of the relationship between sex hormone concentrations and cognitive function in older men, and there is little published literature on ...the relationship of sex hormone concentrations and brain volume as measured by MRI.
To examine the hypothesis that midlife total serum concentrations of testosterone (T), estradiol, estrone, and sex hormone binding globulin (SHBG) predict cognitive task performance and regional brain volumes at 10- to 16-year follow-up, in a longitudinal sample of World War II veteran twin men.
Treating twins as individuals, linear regression models were used, adjusting analyses for age, education, depressive symptomatology, blood pressure, alcohol consumption, years of cigarette smoking, and APOE epsilon4 allele status.
There were no significant associations between sex hormone or SHBG concentrations and performance on a series of cognitive tasks measuring global and executive function, visual and verbal learning and memory. Higher midlife T concentrations were associated with larger hemispheric, frontal, and parietal regional brain volumes and with smaller left occipital brain volume. Higher estradiol and estrone concentrations were also associated with smaller right (estradiol) and both right and left (estrone) occipital volumes, but with no other brain regions. Owing to the multiple comparisons conducted, some significant associations may have occurred by chance.
Overall, the pattern of results suggests a role for sex hormones in brain volume that predates potentially observable associations between sex hormones and cognitive task performance.
Alzheimer's disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent ...work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These 'subtypes' were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of 'typical AD' and a revisiting of tau pathological staging.
Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a ...history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration.
To determine whether epilepsy duration is related to HF atrophy.
We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes.
Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration.
A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures.
Total cerebral, temporal lobe, hippocampal, caudate, and lenticular nuclei volumes were quantified from magnetic resonance images of 21 patients with left temporal lobe epilepsy and medically ...intractable complex partial seizures. These regional brain volumes were compared with the same measures in 19 controls. No significant differences in total cerebral, left temporal lobe, right temporal lobe, or total temporal lobe volumes were found. As expected, left hippocampal volumes were significantly smaller in the patients with epilepsy than in control subjects. The left hippocampus‐to‐right hippocampus volume ratio was significantly lower in patients than in control subjects. In addition to left hippocampal volumes, mean left thalamic, left caudate, and bilateral lenticular volumes were significantly smaller in the patients with epilepsy than in control subjects. The left‐to‐right thalamic volume ratio was also significantly lower in the patients with epilepsy compared with control subjects, but there were no significant group differences in caudate or lenticular ratios. These results show that medically intractable temporal lobe epilepsy is associated with volume loss in brain structures outside the presumably involved hippocampus. The pathophysiological significance of our findings is uncertain. They could be related to the underlying cause of the disorder. However, volume loss also may reflect damage due to involvement of these structures in recurrent seizure activity.
This article describes the development and validation of an instrument to assess cognitively mediated functional abilities in older adults, Everyday Cognition (ECog). The ECog is an informant-rated ...questionnaire comprised of multiple subscales. Confirmatory factor analysis (CFA) was used to examine its factor structure. Convergent validity was evaluated by comparing it to established measures of everyday function. External validity was evaluated by comparing ECog results across different clinical groups cognitively normal, mild cognitive impairment (MCI), dementia. CFA supported a seven-factor model including one global factor and six domain-specific factors (Everyday Memory, Language, Visuospatial Abilities, Planning, Organization, and Divided attention). The ECog correlated with established measures of functional status and global cognition, but only weakly with age and education. The clinical groups performed differently in each domain. In addition to the global factor, the Everyday Memory factor independently differentiated MCI from Normal, while the Everyday Language domain differentiated Dementia from MCI. Different subtypes of MCI also showed different patterns. Results suggest the ECog shows promise as a useful tool for the measurement of general and domain-specific everyday functions in the elderly.
White matter hyperintensities and MRI-defined brain infarcts (BIs) have individually been related to stroke, dementia, and mortality in population-based studies, mainly in older people. Their ...significance in middle-aged community-dwelling persons and the relative importance of these associations remain unclear. We simultaneously assessed the relation of white matter hyperintensities and BI with incident stroke, mild cognitive impairment, dementia, and mortality in a middle-aged community-based cohort.
A total of 2229 Framingham Offspring Study participants aged 62+/-9 years underwent volumetric brain MRI and neuropsychological testing (1999 to 2005). Incident stroke, dementia, and mortality were prospectively ascertained and for 1694 participants in whom a second neuropsychological assessment was performed (2005 to 2007), incident mild cognitive impairment was evaluated. All outcomes were related to white matter hyperintensities volume (WMHV), age-specific extensive WMHV and BI adjusting for age and gender.
Extensive WMHV and BI were associated with an increased risk of stroke (hazard ratio HR=2.28, 95% CI: 1.02 to 5.13; HR=2.84, 95% CI: 1.32 to 6.10). WMHV, extensive WMHV, and BI were associated with an increased risk of dementia (HR=2.22, 95% CI: 1.32 to 3.72; HR=3.97, 95% CI: 1.10 to 14.30; HR=6.12, 95% CI: 1.82 to 20.54) independently of vascular risk factors and interim stroke. WMHV and extensive WMHV were associated with incident amnestic mild cognitive impairment in participants aged > or = 60 years only (OR=2.47, 95% CI: 1.31 to 4.66 and OR=1.49, 95% CI: 1.14 to 1.97). WMHV and extensive WMHV were associated with an increased risk of death (HR=1.38, 95% CI: 1.13 to 1.69; HR=2.27, 95% CI: 1.41 to 3.65) independent of vascular risk factors and of interim stroke and dementia.
In a large community-based sample of middle-aged adults, BI predicted an increased risk of stroke and dementia independent of vascular risk factors. White matter hyperintensities portended an increased risk of stroke, amnestic mild cognitive impairment, dementia, and death independent of vascular risk factors and interim vascular events.
Distinguishing Alzheimer's disease (AD) and frontotemporal dementia (FTD) currently relies on a clinical history and examination, but positron emission tomography with 18F fluorodeoxyglucose ...(FDG-PET) shows different patterns of hypometabolism in these disorders that might aid differential diagnosis. Six dementia experts with variable FDG-PET experience made independent, forced choice, diagnostic decisions in 45 patients with pathologically confirmed AD (n = 31) or FTD (n = 14) using five separate methods: (1) review of clinical summaries, (2) a diagnostic checklist alone, (3) summary and checklist, (4) transaxial FDG-PET scans and (5) FDG-PET stereotactic surface projection (SSP) metabolic and statistical maps. In addition, we evaluated the effect of the sequential review of a clinical summary followed by SSP. Visual interpretation of SSP images was superior to clinical assessment and had the best inter-rater reliability (mean kappa = 0.78) and diagnostic accuracy (89.6%). It also had the highest specificity (97.6%) and sensitivity (86%), and positive likelihood ratio for FTD (36.5). The addition of FDG-PET to clinical summaries increased diagnostic accuracy and confidence for both AD and FTD. It was particularly helpful when raters were uncertain in their clinical diagnosis. Visual interpretation of FDG-PET after brief training is more reliable and accurate in distinguishing FTD from AD than clinical methods alone. FDG-PET adds important information that appropriately increases diagnostic confidence, even among experienced dementia specialists.
The purpose of this study was to investigate whether the Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness are associated with cortical volume and thickness.
...Consecutive subjects participating in a prospective cohort study of aging and mild cognitive impairment enriched for vascular risk factors for atherosclerosis underwent structural MRI scans at 3-T and 4-T MRI at 3 sites. Freesurfer (Version 5.1) was used to obtain regional measures of neocortical volumes (mm3) and thickness (mm). Multiple linear regression was used to determine the association of Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness with cortical volume and thickness.
One hundred fifty-two subjects (82 men) were aged 78 (±7) years, 94 had a clinical dementia rating of 0, 58 had a clinical dementia rating of 0.5, and the mean Mini-Mental State Examination was 28±2. Framingham Cardiovascular Risk Profile score was inversely associated with total gray matter volume and parietal and temporal gray matter volume (adjusted P<0.04). Framingham Cardiovascular Risk Profile was inversely associated with parietal and total cerebral gray matter thickness (adjusted P<0.03). Carotid artery intima-media thickness was inversely associated with thickness of parietal gray matter only (adjusted P=0.04). Including history of myocardial infarction or stroke and radiological evidence of brain infarction, or apolipoprotein E genotype did not alter relationships with Framingham Cardiovascular Risk Profile or carotid artery intima-media thickness.
Increased cardiovascular risk was associated with reduced gray matter volume and thickness in regions also affected by Alzheimer disease independent of infarcts and apolipoprotein E genotype. These results suggest a "double hit" toward developing dementia when someone with incipient Alzheimer disease also has high cardiovascular risk.
Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address ...this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.
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