Increase of theta frequency is associated with reduction in regional cerebral blood flow only in subjects with mild cognitive impairment with higher upper alpha/low alpha EEG frequency power ratio

Background: Several biomarkers have been proposed for detecting Alzheimer's disease (AD) in its earliest stages, that is, in the predementia stage. In an attempt to find noninvasive biomarkers, researchers have investigated the feasibility of neuroimaging tools, such as MRI, SPECT as well as neurophysiological measurements using EEG. Moreover, the increase of EEG alpha3/alpha2 frequency power ratio has been associated with AD-converters subjects with mild cognitive impairment (MCI). Objective: To study the association of alpha3/alpha2 frequency power ratio with regional cerebral blood flow (rCBF) changes in subjects with MCI. Methods: Twenty-seven adult subjects with MCI underwent EEG recording and perfusion single-photon emission computed tomography (SPECT) evaluation. The alpha3/alpha2 frequency power ratio was computed for each subject. Two groups were obtained according to the median values of alpha3/alpha2, at a cut-off of 1.17. Correlation between brain perfusion and EEG markers were detected. Results: Subjects with higher alpha3/alpha2 frequency power ratio showed a constant trend to a lower perfusion than low alpha3/alpha2 group. The two groups were significantly different as about the hippocampal volume and correlation with the theta frequency activity. Conclusion: There is a complex interplay between cerebral blood flow, theta frequency activity, and hippocampal volume in MCI patients with prodromal Alzheimer's disease, characterized by higher EEG alpha3/alpha2 frequency power ratio

Hippocampal and amygdalar local structural differences in elderly patients with schizophrenia

Morphological abnormalities have been reported for the hippocampi and amygdalae in young schizophrenia patients, but very little is known about the pattern of abnormalities in elderly schizophrenia patients. Here we investigated local structural differences in the hippocampi and amygdalae of elderly schizophrenia patients compared with healthy elderly subjects. We also related these differences to clinical symptom severity

P3‐006: Markers of Alzheimer's disease in a naturalistic population attending a memory clinic

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In vivo neuropathology of cortical changes in elderly persons with schizophrenia

BACKGROUND: Elderly schizophrenia patients frequently develop cognitive impairment of unclear etiology. Magnetic resonance imaging (MRI) studies revealed brain structural abnormalities, but the pattern of cortical gray matter (GM) volume and its relationship with cognitive and behavioral symptoms are unknown. METHODS: Magnetic resonance scans were taken from elderly schizophrenia patients (n = 20, age 67 +/- 6 SD, Mini-Mental State Examination [MMSE] 23 +/- 4), Alzheimer's disease (AD) patients (n = 20, age 73 +/- 9, MMSE 22 +/- 4), and healthy elders (n = 20, age 73 +/- 8, MMSE 29 +/- 1). Patients were assessed with a comprehensive neuropsychological and behavioral battery. Cortical pattern matching and a region-of-interest analysis, based on Brodmann areas (BAs), were used to map three-dimensional (3-D) profiles of differences in patterns of gray matter volume among groups. RESULTS: Schizophrenia patients had 10% and 11% lower total left and right GM volume than healthy elders (p < .001) and 7% and 5% more than AD patients (p = .06 and ns). Regions that had both significantly less gray matter than control subjects and gray matter volume as low as AD mapped to the cingulate gyrus and orbitofrontal cortex (BA 30, 23, 24, 32, 25, 11). The strongest correlate of gray matter volume in elderly schizophrenia patients, although nonsignificant, was the positive symptom subscale of the Positive and Negative Syndrome Scale, mapping to the right anterior cingulate area (r = .42, p = .06). CONCLUSIONS: The orbitofrontal/cingulate region had low gray matter volume in elderly schizophrenia patients. Neither cognitive impairment nor psychiatric symptoms were significantly associated with structural differences, even if positive symptoms tended to be associated with increased gray matter volume in this area

A standardized [18F]-FDG-PET template for spatial normalization in statistical parametric mapping of dementia

[18F]-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) is a widely used diagnostic tool that can detect and quantify pathophysiology, as assessed through changes in cerebral glucose metabolism. [18F]-FDG PET scans can be analyzed using voxel-based statistical methods such as Statistical Parametric Mapping (SPM) that provide statistical maps of brain abnormalities in single patients. In order to perform SPM, a "spatial normalization" of an individual's PET scan is required to match a reference PET template. The PET template currently used for SPM normalization is based on [15O]-H2O images and does not resemble either the specific metabolic features of [18F]-FDG brain scans or the specific morphological characteristics of individual brains affected by neurodegeneration. Thus, our aim was to create a new [18F]-FDG PET aging and dementia-specific template for spatial normalization, based on images derived from both age-matched controls and patients. We hypothesized that this template would increase spatial normalization accuracy and thereby preserve crucial information for research and diagnostic purposes. We investigated the statistical sensitivity and registration accuracy of normalization procedures based on the standard and new template-at the single-subject and group level-independently for subjects with Mild Cognitive Impairment (MCI), probable Alzheimer's Disease (AD), Frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB). We found a significant statistical effect of the population-specific FDG template-based normalisation in key anatomical regions for each dementia subtype, suggesting that spatial normalization with the new template provides more accurate estimates of metabolic abnormalities for single-subject and group analysis, and therefore, a more effective diagnostic measure

Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI.

BackgroundThe aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI).MethodsMagnetic resonance imaging, F-18 fluorodeoxyglucose positron emission tomography markers, and Alzheimer's Disease Assessment Scale-cognitive subscale were compared in terms of effect size and statistical power over different follow-up periods in 2 MCI groups, selected from Alzheimer's Disease Neuroimaging Initiative data set based on cerebrospinal fluid (abnormal cerebrospinal fluid Aβ1-42 concentration-ABETA+) or magnetic resonance imaging evidence of Alzheimer disease (positivity to hippocampal atrophy-HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms.ResultsSeventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency.ConclusionThese findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials