[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.

The core biomarker pattern is in line with the current pathophysiologic model of AD. Fully normal and fully abnormal pattern is associated with exceptional and universal development of dementia. Cases not in line might be due to atypical neurobiology or inaccurate thresholds for biomarker (ab)normality.

Objectives: The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI). Methods:We measured markers of amyloid pathology (CSF b-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [18 F]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A1/A2 and N1/N2 based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A2N1 cases.Results: The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71%(60/85) in A2N2, A1N2, SNAP, and A1N1, respectively; the proportion of APOE e4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A1N2 and A1N1 groups (p # 0.005). Hypometabolism in SNAP patients was comparable to A1N1 patients (p 5 0.154), while hippocampal atrophy was more severe in SNAP patients (p 5 0.002). Compared with A2N2, SNAP and A1N1 patients had significant risk of progressive cognitive deterioration (hazard ratio 5 2.7 and 3.8, p 5 0.016 and p , 0.001), while A1N2 patients did not (hazard ratio 5 1.13, p 5 0.771). In A1N2 and A1N1 groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r 5 0.42, p 5 0.073). The amyloid cascade hypothesis 1,2 has so far dominated the Alzheimer disease (AD) field. Jack et al. Conclusions:3,4 proposed a dynamic model that relates disease stage to the best established biomarkers of AD pathology. Based on this, a National Institute on Aging-Alzheimer's Association task force developed recommendations for the diagnosis of preclinical AD based on biomarkers of amyloidosis and neuronal injury.5 Soon afterward, these criteria were operationalized and a

Previous evidence has shown that resting delta and alpha electroencephalographic (EEG) rhythms are abnormal in patients with Alzheimer's disease (AD) and its potential preclinical stage (mild cognitive impairment, MCI). Here, we tested the hypothesis that these EEG rhythms are correlated with memory and attention in the continuum across MCI and AD. Resting eyes-closed EEG data were recorded in 34 MCI and 53 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). These sources were correlated with neuropsychological measures such as Rey list immediate recall (word short-term memory), Rey list delayed recall (word medium-term memory), Digit span forward (immediate memory for digits probing focused attention), and Corsi span forward (visuo-spatial immediate memory probing focused attention). A statistically significant negative correlation (Bonferroni corrected, P < 0.05) was observed between Corsi span forward score and amplitude of occipital or temporal delta sources across MCI and AD subjects. Furthermore, a positive correlation was shown between Digit span forward score and occipital alpha 1 sources (Bonferroni corrected, P < 0.05). These results suggest that cortical sources of resting delta and alpha rhythms correlate with neuropsychological measures of immediate memory based on focused attention in the continuum of MCI and AD subjects.

Progressive brain atrophy is believed to be the Alzheimer's disease (AD) marker with the greatest evidence for validity. Mapping the topography of cortical atrophy throughout the stages of severity may allow the neural networks affected to be identified. Twenty healthy elderly persons (OH, MMSE 29.1 +/- 1.0), 11 patients with incipient AD (iAD, 26.5 +/- 2.0), 15 with mild AD (miAD, 23.5 +/- 2.2), and 15 with moderate AD (moAD, 16.5 +/- 2.0) underwent 3D magnetic resonance. Cortical pattern matching analysis was performed and maps of percent differences in gray matter distribution were computed between the following groups: iAD versus OH, miAD versus iAD, and moAD versus miAD. Compared to OH, iAD patients exhibited a mean cortical gray matter loss of 9-20% in areas encompassing the polysynaptic hippocampal pathway (posterior cingulate/retrosplenial and medial temporal cortex) and subgenual/orbitofrontal cortices, and a less widespread loss of 5-11% in other neocortical areas. Compared to iAD, miAD featured widespread mean gray matter loss of 14-19% in areas encompassing the direct hippocampal pathway (temporal pole, temporoparietal association cortex, and dorsal prefrontal cortex), sensorimotor, and visual cortex, with a less marked loss (7-9%) in the polysynaptic pathway areas. Compared to miAD, only atrophy in the primary sensorimotor cortex was still relatively marked in moAD, with a mean gray matter loss of 10-11%; the loss in other regions was generally below 10%. These findings suggest that the polysynaptic hippocampal pathway is affected in iAD, the direct pathway and sensorimotor and visual networks are affected in moAD, and the sensorimotor network is affected in moAD.