Lacaziosis-like disease among bottlenose dolphins Tursiops truncatus photographed in Golfo Dulce, Costa Rica.

Lacaziosis (also known as lobomycosis) is a chronic dermal disease caused by the fungal agent Lacazia loboi, which affects both humans and dolphins. Photographic data have been used to identify lacaziosis-like disease (LLD) among dolphins in the waters of North and South America, and here we report LLD in bottlenose dolphins Tursiops truncatus off the coast of Costa Rica, the first reporting in Central American waters. During the periods of 1991 to 1992 and 2010 to 2011, 3 research teams conducted separate dolphin surveys in the Pacific tropical fiord Golfo Dulce, and each documented skin lesions in the resident population of bottlenose dolphins. Photo-ID records were used to identify LLD-affected bottlenose dolphins and to assess their lesions. Findings showed between 13.2 and 16.1% of the identified dolphins exhibited lesions grossly resembling lacaziosis. By combining efforts and cross-referencing photographic data, the teams explored the presence of LLD in Golfo Dulce over a time gap of approximately 20 yr. Our findings expand the geographical range of the disease and offer insight into its longevity within a given population of dolphins.

Single-domain amnestic mild cognitive impairment identified by cluster analysis predicts Alzheimer's disease in the european prospective DESCRIPA study.

BACKGROUND/AIMS: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). METHODS: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e.g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE ≥28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. RESULTS: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (Aß42, t-tau, APOE ε4, and medial temporal atrophy), compared to SCI or naMCI. CONCLUSION: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings.

Inflammation markers correlate with common carotid intima-media thickness in patients perinatally infected with human immunodeficiency virus 1.

OBJECTIVES: To investigate common carotid intima-media thickness in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (HIV-1). METHODS: We conducted a cross-sectional observational study. Human immunodeficiency virus 1-infected patients were compared with age-, sex-, and body mass index-matched healthy participants. Common carotid intima-media thickness was measured in all participants on both sides of the neck, and the mean intima-media thickness was calculated. Metabolic parameters and markers of inflammation were measured only in HIV-1-infected patients. Statistical analysis was performed by multiple regression and by a matrix of Pearson correlation coefficients. The Student t test was used to compare mean common carotid intima-media thickness values between groups. RESULTS: Forty patients (21 female) with HIV-1 infection acquired from birth with a mean age ± SD of 16.3 ± 4.7 years and 27 healthy participants (11 female) with a mean age of 17.7 ± 4.6 years were included in the study. Mean common carotid intima-media thickness in the HIV-1-infected group (0.450 ± 0.088 mm) was significantly higher (P < .05) than in the control group (0.407 ± 0.079 mm). No significant association was found between intima-media thickness and a specific antiretroviral regimen, exposure to combined antiretroviral agents, and HIV status. In multiple regression analyses, higher levels of insulin (P= .007) and elevated levels of glycated hemoglobin (P= .01) were associated with intima-media thickness changes. CONCLUSIONS: Patients perinatally infected with HIV have increased common carotid intima-media thickness compared with healthy individuals. These changes were more pronounced with increasing age and inflammation markers. Interventions that improve cardiovascular risk profiles should be considered in HIV-infected young adults.

Effectiveness of Respiratory Muscles Training by Voluntary Isocapnic Hyperpnea Versus Inspiratory Threshold Loading on Intercostales and Vastus Lateralis Muscles Deoxygenation Induced by Exercise in Physically Active Adults.

Respiratory muscle training (RMT) improves physical performance, although it is still debated whether this effect depends on the type of training. The purpose of this study was to compare the effects of two different types of RMT, i.e., voluntary isocapnic hyperpnea (VIH) and inspiratory threshold loading (ITL), on the deoxygenation of intercostal (ΔSmO2-m. intercostales) and vastus lateralis (ΔSmO2-m. vastus lateralis) muscles during exercise. Twenty-four participants performed eight weeks of RMT by: (i) VIH (3 days·week-1 for 12 min at 60% maximal voluntary ventilation) or (ii) ITL (5 sets·week-1 of 30 breaths·minute-1 at 60% maximal inspiratory pressure). Cardiopulmonary exercise testing (CPET) included ΔSmO2 (the change from baseline to end of test) of intercostal and vastus lateralis muscles. After RMT, both groups showed decreased ΔSmO2-m. intercostales (VIH = 12.8 ± 14.6%, p = 0.04 (effect size, ES = 0.59), and ITL = 8.4 ± 9.8%, p = 0.04 (ES = 0.48)), without a coincident change of ∆SmO2-m. vastus lateralis. ITL training induced higher V˙O2-peak absolute values than VIH (mean Δ post-pre, ITL = 229 ± 254 mL·min-1 [95% CI 67-391] vs. VIH, 39 ± 153 mL·min-1 [95% CI -58-136.0], p = 0.01). In conclusion, both RMT improved the balance between supply and oxygen consumption levels of m. intercostales during CPET, with ITL also inducing an increase of aerobic capacity.

The short cognitive evaluation battery in cognitive disorders of the elderly--Italian version.

AIMS: To validate the Italian version of the Short Cognitive Evaluation Battery (SCEB), consisting of 4 tests (temporal orientation, five words, clock drawing and verbal fluency) in healthy controls (CONT), patients with mild Alzheimer's disease (AD), mild cognitive impairment (MCI), and major depressive disorder (DEP). METHODS: Twenty-nine AD patients (mean Mini-Mental State Examination, MMSE, score: 22.1 ± 3.1), 27 MCI patients (mean MMSE score: 26.5 ± 2.0), 27 depressed patients (mean MMSE score: 26.9 ± 2.8), and 48 controls (mean MMSE score: 29.7 ± 0.5) were enrolled. RESULTS: MANCOVA showed highly significant (p < 0.0001) difference among groups. As for total SCEB score, AD were separated from CONT with high accuracy (93%; with sensitivity 93%, specificity 92%, area under ROC curve, AUC, 0.96) and from DEP with satisfying accuracy (84%; with sensitivity 76%, specificity 93%, AUC 0.84). Results in MCI versus CONT comparison yielded more moderate accuracy (80%; with sensitivity 70%, specificity 87%, AUC 0.80), which increased in the subgroup of MCI patients who later converted to AD (85%; with sensitivity 75%, specificity 83%, AUC 0.86). The direct comparison between MCI converters and nonconverters did not yield accurate results. CONCLUSION: The Italian version of the SCEB is a short (between 6 min in CONT and 12 min in DEP) screening tool in cognitive disorders of the elderly, and is potentially useful in clinical practice.

Local MRI analysis approach in the diagnosis of early and prodromal Alzheimer's disease.

BACKGROUND: Medial temporal lobe (MTL) atrophy is one of the key biomarkers to detect early neurodegenerative changes in the course of Alzheimer's disease (AD). There is active research aimed at identifying automated methodologies able to extract accurate classification indexes from T1-weighted magnetic resonance images (MRI). Such indexes should be fit for identifying AD patients as early as possible. SUBJECTS: A reference group composed of 144AD patients and 189 age-matched controls was used to train and test the procedure. It was then applied on a study group composed of 302 MCI subjects, 136 having progressed to clinically probable AD (MCI-converters) and 166 having remained stable or recovered to normal condition after a 24month follow-up (MCI-non converters). All subjects came from the ADNI database. METHODS: We sampled the brain with 7 relatively small volumes, mainly centered on the MTL, and 2 control regions. These volumes were filtered to give intensity and textural MRI-based features. Each filtered region was analyzed with a Random Forest (RF) classifier to extract relevant features, which were subsequently processed with a Support Vector Machine (SVM) classifier. Once a prediction model was trained and tested on the reference group, it was used to compute a classification index (CI) on the MCI cohort and to assess its accuracy in predicting AD conversion in MCI patients. The performance of the classification based on the features extracted by the whole 9 volumes is compared with that derived from each single volume. All experiments were performed using a bootstrap sampling estimation, and classifier performance was cross-validated with a 20-fold paradigm. RESULTS: We identified a restricted set of image features correlated with the conversion to AD. It is shown that most information originate from a small subset of the total available features, and that it is enough to give a reliable assessment. We found multiple, highly localized image-based features which alone are responsible for the overall clinical diagnosis and prognosis. The classification index is able to discriminate Controls from AD with an Area Under Curve (AUC)=0.97 (sensitivity ≃89% at specificity ≃94%) and Controls from MCI-converters with an AUC=0.92 (sensitivity ≃89% at specificity ≃80%). MCI-converters are separated from MCI-non converters with AUC=0.74(sensitivity ≃72% at specificity ≃65%). FINDINGS: The present automated MRI-based technique revealed a strong relationship between highly localized baseline-MRI features and the baseline clinical assessment. In addition, the classification index was also used to predict the probability of AD conversion within a time frame of two years. The definition of a single index combining local analysis of several regions can be useful to detect AD neurodegeneration in a typical MCI population.

Stability of clinical condition in mild cognitive impairment is related to cortical sources of alpha rhythms: an electroencephalographic study.

Previous evidence has shown that resting eyes-closed cortical alpha rhythms are higher in amplitude in mild cognitive impairment (MCI) than Alzheimer's disease (AD) subjects (Babiloni et al. [2006a]: Human Brain Mapp 27:162-172; [2006b]: Clin Neurophysiol 117:252-268; [2006c]: Neuroimage 29:948-964; [2006d]: Ann Neurol 59:323-334; [2006e]: Clin Neurophysiol 117:1113-1129; [2006f]: Neuroimage 31:1650-1665). This study tested the hypothesis that, in amnesic MCI subjects, high amplitude of baseline cortical alpha rhythms is related to long-term stability of global cognition on clinical follow-up. Resting electroencephalographic (EEG) data were recorded in 100 amnesic MCI subjects during eyes-closed condition. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), and beta2 (20-30 Hz). Cortical EEG sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Global cognition was indexed by mini mental state evaluation (MMSE) score at the time of EEG recordings (baseline) and about after 1 year. Based on the MMSE percentage difference between baseline and 1-year follow-up (MMSEvar), the MCI subjects were retrospectively divided into three arbitrary groups: DECREASED (MMSEvar ≤ -4%; N = 43), STABLE (MMSEvar ≈ 0; N = 27), and INCREASED (MMSEvar ≥ +4%; N = 30). Subjects' age, education, individual alpha frequency, gender, and MMSE scores were used as covariates for statistical analysis. Baseline posterior cortical sources of alpha 1 rhythms were higher in amplitude in the STABLE than in the DECREASED and INCREASED groups. These results suggest that preserved resting cortical neural synchronization at alpha frequency is related to a long-term (1 year) stable cognitive function in MCI subjects. Future studies should use serial MMSE measurements to confirm and refine the present results.

Brain perfusion correlates of cognitive and nigrostriatal functions in de novo Parkinson's disease.

PURPOSE: Subtle cognitive impairment is recognized in the first stages of Parkinson's disease (PD), including executive, memory and visuospatial dysfunction, but its pathophysiological basis is still debated. METHODS: Twenty-six consecutive, drug-naïve, de novo PD patients underwent an extended neuropsychological battery, dopamine transporter (DAT) and brain perfusion single photon emission computed tomography (SPECT). We previously reported that nigrocaudate impairment correlates with executive functions, and nigroputaminal impairment with visuospatial abilities. Here perfusion SPECT was first compared between the PD group and age-matched controls (CTR). Then, perfusion SPECT was correlated with both DAT SPECT and four neuropsychological factors by means of voxel-based analysis (SPM8) with a height threshold of p < 0.005 at peak level and p < 0.05 false discovery rate-corrected at cluster level. Both perfusion and DAT SPECT images were flipped in order to have the more affected hemisphere (MAH), defined clinically, on the same side. RESULTS: Significant hypoperfusion was found in an occipital area of the MAH in PD patients as compared to CTR. Executive functions directly correlated with brain perfusion in bilateral posterior cingulate cortex and precuneus in the less affected hemisphere (LAH), while verbal memory directly correlated with perfusion in the precuneus, inferior parietal lobule and superior temporal gyrus in the LAH. Furthermore, positive correlation was highlighted between nigrocaudate and nigroputaminal impairment and brain perfusion in the precuneus, posterior cingulate and parahippocampal gyri of the LAH. CONCLUSION: These data support the evidence showing an early involvement of the cholinergic system in the early cognitive dysfunction and point to a more relevant role of parietal lobes and posterior cingulate in executive functions in PD.

Assessment of dementia in ethnic minority patients in Europe: a European Alzheimer's Disease Consortium survey.

BACKGROUND: In most European countries the ethnic minority migrant populations are currently reaching an age where dementia becomes an increasingly important issue. There is no European consensus on good clinical practice with these patient groups, who often have special needs and expectations with regard to dementia services. METHODS: A survey was conducted in clinical dementia centers in 15 European countries. Questionnaires focusing on different points in the clinical assessment of dementia in ethnic minority patients were mailed to leading dementia experts of the European Alzheimer's Disease Consortium. RESULTS: Thirty-six centers from 15 countries responded to the survey. Ethnic minority patients were seen on a regular basis in 69% of these centers. The diagnostic evaluation was in accordance with evidence-based clinical guidelines in 84-100% of the centers, but most centers performed cognitive assessment with instruments that are only validated in Western cultures and frequently relied on family members for interpretation. Diagnostic evaluation of the patients was considered to be challenging in 64% of the centers, mainly because of communication problems and lack of adequate assessment tools. In general, there were few indicators of culturally sensitive dementia services in the centers. CONCLUSIONS: Ethnic minority patients are seen on a regular basis in European dementia clinics. Assessment of such patients is difficult for a number of reasons. Results from this study show that the most challenging issues are communication problems and assessment of cognitive function where there is a need to develop specific tests for ethnic minority patients.

Phosphorylation of APP-CTF-AICD domains and interaction with adaptor proteins: signal transduction and/or transcriptional role--relevance for Alzheimer pathology.

In recent decades, the study of the amyloid precursor protein (APP) and of its proteolytic products carboxy terminal fragment (CTF), APP intracellular C-terminal domain (AICD) and amyloid beta has been mostly focussed on the role of APP as a producer of the toxic amyloid beta peptide. Here, we reconsider the role of APP suggesting, in a provocative way, the protein as a central player in a putative signalling pathway. We highlight the presence in the cytosolic tail of APP of the YENPTY motif which is typical of tyrosine kinase receptors, the phosphorylation of the tyrosine, serine and threonine residues, the kinases involved and the interaction with intracellular adaptor proteins. In particular, we examine the interaction with Shc and Grb2 regulators, which through the activation of Ras proteins elicit downstream signalling events such as the MAPK pathway. The review also addresses the interaction of APP, CTFs and AICD with other adaptor proteins and in particular with Fe65 for nuclear transcriptional activity and the importance of phosphorylation for sorting the secretases involved in the amyloidogenic or non-amyloidogenic pathways. We provide a novel perspective on Alzheimer's disease pathogenesis, focussing on the perturbation of the physiological activities of APP-CTFs and AICD as an alternative perspective from that which normally focuses on the accumulation of neurotoxic proteolytic fragments.

Mapping brain morphological and functional conversion patterns in amnestic MCI: a voxel-based MRI and FDG-PET study.

PURPOSE: To reveal the morphological and functional substrates of memory impairment and conversion to Alzheimer disease (AD) from the stage of amnestic mild cognitive impairment (aMCI). METHODS: Brain MRI and FDG-PET were performed in 20 patients with aMCI and 12 controls at baseline. During a mean follow-up of about 2 years, 9 patients developed AD (converters), and 11 did not (nonconverters). All images were processed with SPM2. FDG-PET and segmented grey matter (GM) images were compared in: (1) converters versus controls, (2) nonconverters versus controls, and (3) converters versus nonconverters. RESULTS: As compared to controls, converters showed lower GM density in the left parahippocampal gyrus and both thalami, and hypometabolism in the precuneus, posterior cingulate and superior parietal lobule in the left hemisphere. Hypometabolism was found in nonconverters as compared to controls in the left precuneus and posterior cingulated gyrus. As compared to nonconverters, converters showed significant hypometabolism in the left middle and superior temporal gyri. CONCLUSION: The discordant topography between atrophy and hypometabolism reported in AD is already present at the aMCI stage. Posterior cingulate-precuneus hypometabolism seemed to be an early sign of memory deficit, whereas hypometabolism in the left temporal cortex marked the conversion to AD.

Cognitive-nigrostriatal relationships in de novo, drug-naïve Parkinson's disease patients: a [I-123]FP-CIT SPECT study.

To unveil cognitive-nigrostriatal correlations in Parkinson's disease (PD), 30 de novo, drug-naïve PD patients and 15 patients with essential tremor (Controls, CTR) underwent a neuropsychological (NPS) battery and brain SPECT with [I-123]Ioflupane, as a biomarker of nigrostriatal function. Automatic extraction of uptake at caudate and putamen level was conducted through the BasGan software, also allowing partial volume effect correction. Because of the multicollinearity among neuropsychological tests and among SPECT variables, factor analysis was applied to 16 neuropsychological scores; moreover, the four SPECT variables were merged into a mean SPECT value (mSPECT). Factor analysis identified four NPS factors: a dys-executive (NPS-EX), a visuospatial (NPS-VS), a verbal memory (NPS-VM), and a "mixed" (NPD-MIX) factor. In PD group, there were inverse correlations between UPDRS-III score and both NPS-VS (P < 0.01) and mSPECT (P < 0.05), and a direct correlation between mSPECT and NPS-EX (P < 0.05). Post hoc analysis showed a direct correlation between NPS-EX and caudate uptake in both hemispheres (P < 0.05). Moreover, inverse correlations were found between UPDRS-III and, respectively, putamen uptake in the less affected hemisphere (P < 0.01), and putamen and caudate uptake in the more affected hemisphere (P < 0.05). In CTR, no correlation was found between mSPECT and either NPS or GDS values. Nigro-caudate function affects executive capabilities in PD but not in CTR, which appears to be unrelated to the disease motor severity at its onset. Instead, PD motor severity is related to nigro-putaminal impairment and visuospatial dysfunction. The role of these data as predictive features of cognitive decline and eventually dementia remains to be established in longitudinal studies.

Lower perfusion pressure during hypothermic cardiopulmonary bypass is associated with decreased cerebral blood flow and impaired memory performance 6 months postoperatively.

OBJECTIVES: We undertook to determine the influence of perfusion pressure during hypothermic cardiopulmonary bypass (CPB) on cerebral blood flow (CBF) and cognitive memory outcome at 6 months postoperatively. METHODS: Nineteen patients who underwent hypothermic nonpulsatile CPB for elective coronary artery bypass (CAB) surgery were evaluated by (133)Xe measurement of the CBF and by the Incidental Memory Assessment for evaluating cognitive memory (IMTscore), both at baseline before the operation (T(1)) and again at 5 to 6 months postoperatively (T(2)). RESULTS: Overall, the mean CBF fell significantly from 39 +/- 5 mL.(100 g)(-1).min(-1) at T(1) to 33 +/- 3 mL.(100 g)(-1).min(-1) at T(2) (P < .001). The decrease in CBF from T(1) to T(2) (DeltaCBF(2-1)) correlated with a significant reduction in the IMTscore from T1 to T2 (DeltaIMTscore(2-1)) (P < .001) and with a mean arterial pressure during CPB (MAPCPB) of <60 mm Hg (P = .05). Cluster analysis of DeltaCBF(2-1) and DeltaIMTscore(2-1) demonstrated that the patients with the greatest decrease in CBF showed the greatest decrease in IMTscore, whereas cluster analysis of DeltaCBF(2-1) and MAPCPB indicated that patients with a perfusion pressure maintained at a mean of <60 mm Hg during CPB were prone to a greater decrease in later postoperative CBF. CONCLUSION: This study demonstrated that a MAPCPB of <60 mm Hg during CPB was associated with a significant decrease in CBF 6 months after CAB surgery and with an associated decrease in memory performance.

Amnestic mild cognitive impairment in Parkinson's disease: a brain perfusion SPECT study.

The purpose of this study was to investigate cortical dysfunction in Parkinson's disease (PD) patients with amnestic deficit (PD-MCI). Perfusion single photon emission computed tomography was performed in 15 PD-MCI patients and compared (statistical parametric mapping [SPM2]) with three groups, i.e., healthy subjects (CTR), cognitively intact PD patients (PD), and common amnestic MCI patients (aMCI). Age, depression, and UPDRS-III scores were considered as confounding variables. PD-MCI group (P < 0.05, false discovery rate-corrected for multiple comparisons) showed relative hypoperfusion in bilateral posterior parietal lobe and in right occipital lobe in comparison to CTR. As compared to aMCI, MCI-PD demonstrated hypoperfusion in bilateral posterior parietal and occipital areas, mainly right cuneus and angular gyrus, and left precuneus and middle occipital gyrus. With a less conservative threshold (uncorrected P < 0.01), MCI-PD showed hypoperfusion in a left parietal region, mainly including precuneus and inferior parietal lobule, and in a right temporal-parietal-occipital region, including middle occipital and superior temporal gyri, and cuneus-precuneus, as compared to PD. aMCI versus PD-MCI showed hypoperfusion in bilateral medial temporal lobe, anterior cingulate, and left orbitofrontal cortex. PD-MCI patients with amnestic deficit showed cortical dysfunction in bilateral posterior parietal and occipital lobes, a pattern that can be especially recognized versus both controls and common aMCI patients, and to a lesser extent versus cognitively intact PD. The relevance of this pattern in predicting dementia should be evaluated in longitudinal studies.

Automatic analysis of medial temporal lobe atrophy from structural MRIs for the early assessment of Alzheimer disease.

The purpose of this study is to develop a software for the extraction of the hippocampus and surrounding medial temporal lobe (MTL) regions from T1-weighted magnetic resonance (MR) images with no interactive input from the user, to introduce a novel statistical indicator, computed on the intensities in the automatically extracted MTL regions, which measures atrophy, and to evaluate the accuracy of the newly developed intensity-based measure of MTL atrophy to (a) distinguish between patients with Alzheimer disease (AD), patients with amnestic mild cognitive impairment (aMCI), and elderly controls by using established criteria for patients with AD and aMCI as the reference standard and (b) infer about the clinical outcome of aMCI patients. For the development of the software, the study included 61 patients with mild AD (17 men, 44 women; mean age +/- standard deviation (SD), 75.8 years +/- 7.8; Mini Mental State Examination (MMSE) score, 24.1 +/- 3.1), 42 patients with aMCI (11 men, 31 women; mean age +/- SD, 75.2 years +/- 4.9; MMSE score, 27.9 +/- 1.9), and 30 elderly healthy controls (10 men, 20 women; mean age +/- SD, 74.7 years +/- 5.2; MMSE score, 29.1 +/- 0.8). For the evaluation of the statistical indicator, 150 patients with mild AD (62 men, 88 women; mean age +/- SD, 76.3 years +/- 5.8; MMSE score, 23.2 +/- 4.1), 247 patients with aMCI (143 men, 104 women; mean age +/- SD, 75.3 years +/- 6.7; MMSE score, 27.0 +/- 1.8), and 135 elderly healthy controls (61 men, 74 women; mean age +/- SD, 76.4 years +/- 6.1). Fifty aMCI patients were evaluated every 6 months over a 3 year period to assess conversion to AD. For each participant, two subimages of the MTL regions were automatically extracted from T1-weighted MR images with high spatial resolution. An intensity-based MTL atrophy measure was found to separate control, MCI, and AD cohorts. Group differences were assessed by using two-sample t test. Individual classification was analyzed by using receiver operating characteristic (ROC) curves. Compared to controls, significant differences in the intensity-based MTL atrophy measure were detected in both groups of patients (AD vs controls, 0.28 +/- 0.03 vs 0.34 +/- 0.03, P < 0.001; aMCI vs controls, 0.31 +/- 0.03 vs 0.34 +/- 0.03, P < 0.001). Moreover, the subgroup of aMCI converters was significantly different from controls (0.27 +/- 0.034 vs 0.34 +/- 0.03, P < 0.001). Regarding the ROC curve for intergroup discrimination, the area under the curve was 0.863 for AD patients vs controls, 0.746 for all aMCI patients vs controls, and 0.880 for aMCI converters vs controls. With specificity set at 85%, the sensitivity was 74% for AD vs controls, 45% for aMCI vs controls, and 83% for aMCI converters vs controls. The automated analysis of MTL atrophy in the segmented volume is applied to the early assessment of AD, leading to the discrimination of aMCI converters with an average 3 year follow-up. This procedure can provide additional useful information in the early diagnosis of AD.

Principal component analysis in mild and moderate Alzheimer's disease--a novel approach to clinical diagnosis.

Principal component analysis (PCA) provides a method to explore functional brain connectivity. The aim of this study was to identify regional cerebral blood flow (rCBF) distribution differences between Alzheimer's disease (AD) patients and controls (CTR) by means of volume of interest (VOI) analysis and PCA. Thirty-seven CTR, 30 mild AD (mildAD) and 27 moderate AD (modAD) subjects were investigated using single photon emission computed tomography with (99m)Tc-hexamethylpropylene amine oxime. Analysis of covariance (ANCOVA), PCA, and discriminant analysis (DA) were performed on 54 VOIs. VOI analysis identified in both mildAD and modAD subjects a decreased rCBF in six regions. PCA in mildAD subjects identified four principal components (PCs) in which the correlated VOIs showed a decreased level of rCBF, including regions that are typically affected early in the disease. In five PCs, including parietal-temporal-limbic cortex, and hippocampus, a significantly lower rCBF in correlated VOIs was found in modAD subjects. DA significantly discriminated the groups. The percentage of subjects correctly classified was 95, 70, and 81 for CTR, mildAD and modAD groups, respectively. PCA highlighted, in mildAD and modAD, relationships not evident when brain regions are considered as independent of each other, and it was effective in discriminating groups. These findings may allow neurophysiological inferences to be drawn regarding brain functional connectivity in AD that might not be possible with univariate analysis.

Principal component analysis of FDG PET in amnestic MCI.

PURPOSE: The purpose of the study is to evaluate the combined accuracy of episodic memory performance and (18)F-FDG PET in identifying patients with amnestic mild cognitive impairment (aMCI) converting to Alzheimer's disease (AD), aMCI non-converters, and controls. METHODS: Thirty-three patients with aMCI and 15 controls (CTR) were followed up for a mean of 21 months. Eleven patients developed AD (MCI/AD) and 22 remained with aMCI (MCI/MCI). (18)F-FDG PET volumetric regions of interest underwent principal component analysis (PCA) that identified 12 principal components (PC), expressed by coarse component scores (CCS). Discriminant analysis was performed using the significant PCs and episodic memory scores. RESULTS: PCA highlighted relative hypometabolism in PC5, including bilateral posterior cingulate and left temporal pole, and in PC7, including the bilateral orbitofrontal cortex, both in MCI/MCI and MCI/AD vs CTR. PC5 itself plus PC12, including the left lateral frontal cortex (LFC: BAs 44, 45, 46, 47), were significantly different between MCI/AD and MCI/MCI. By a three-group discriminant analysis, CTR were more accurately identified by PET-CCS + delayed recall score (100%), MCI/MCI by PET-CCS + either immediate or delayed recall scores (91%), while MCI/AD was identified by PET-CCS alone (82%). PET increased by 25% the correct allocations achieved by memory scores, while memory scores increased by 15% the correct allocations achieved by PET. CONCLUSION: Combining memory performance and (18)F-FDG PET yielded a higher accuracy than each single tool in identifying CTR and MCI/MCI. The PC containing bilateral posterior cingulate and left temporal pole was the hallmark of MCI/MCI patients, while the PC including the left LFC was the hallmark of conversion to AD.

Brain SPECT in subtypes of mild cognitive impairment. Findings from the DESCRIPA multicenter study.

The Development of Screening Guidelines and Clinical Criteria of Predementia Alzheimer's Disease (DESCRIPA) multicenter study enrolled patients with MCI or subjective cognitive complaints (SUBJ), a part of whom underwent optional brain perfusion SPECT. These patients were classified as SUBJ (n = 23), nonamnestic MCI (naMCI; n = 17) and amnestic MCI (aMCI; n = 40) based on neuropsychology. Twenty healthy subjects formed the control (CTR) group. Volumetric regions of interest (VROI) analysis was performed in six associative cortical areas in each hemisphere. ANOVA for repeated measures, corrected for age and center, showed significant differences between groups (p = 0.01) and VROI (p < 0.0001) with a significant group-region interaction (p = 0.029). In the post hoc comparison, SUBJ did not differ from CTR. aMCI disclosed reduced uptake in the left hippocampus and bilateral temporal cortex (compared with CTR) or in the left hippocampus and bilateral parietal cortex (compared with SUBJ). In the naMCI group, reduced VROI values were found in the bilateral temporal cortex and right frontal cortex. In the comparison between aMCI and naMCI, the former had lower values in the left parietal cortex and precuneus. Discriminant analysis between SUBJ/CTR versus all MCI patients allowed correct allocations in 73 % of cases. Mean VROI values were highly correlated (p < 0.0001) with the learning measure of a verbal memory test, especially in the bilateral precunei and parietal cortex and in the left hippocampus. In a subset of 70 patients, mean VROI values showed a significant correlation (p < 0.05) with the white matter hyperintensities score on MRI. In conclusion, MCI subtypes have different perfusion patterns. The aMCI group exhibited a pattern that is typical of early Alzheimer's disease, while the naMCI group showed a more anterior pattern of hypoperfusion. Instead, a homogeneous group effect was lacking in SUBJ.

Is it possible to automatically distinguish resting EEG data of normal elderly vs. mild cognitive impairment subjects with high degree of accuracy?

OBJECTIVE: It has been shown that a new procedure (implicit function as squashing time, IFAST) based on artificial neural networks (ANNs) is able to compress eyes-closed resting electroencephalographic (EEG) data into spatial invariants of the instant voltage distributions for an automatic classification of mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects with classification accuracy of individual subjects higher than 92%. METHODS: Here we tested the hypothesis that this is the case also for the classification of individual normal elderly (Nold) vs. MCI subjects, an important issue for the screening of large populations at high risk of AD. Eyes-closed resting EEG data (10-20 electrode montage) were recorded in 171 Nold and in 115 amnesic MCI subjects. The data inputs for the classification by IFAST were the weights of the connections within a nonlinear auto-associative ANN trained to generate the instant voltage distributions of 60-s artifact-free EEG data. RESULTS: The most relevant features were selected and coincidently the dataset was split into two halves for the final binary classification (training and testing) performed by a supervised ANN. The classification of the individual Nold and MCI subjects reached 95.87% of sensitivity and 91.06% of specificity (93.46% of accuracy). CONCLUSIONS: These results indicate that IFAST can reliably distinguish eyes-closed resting EEG in individual Nold and MCI subjects. SIGNIFICANCE: IFAST may be used for large-scale periodic screening of large populations at risk of AD and personalized care.

Multi-center comparison of medial temporal atrophy in patients with Alzheimer's disease--data from the ICTUS study.

OBJECTIVE: To study multi-center variability of medial temporal lobe atrophy (MTA) in patients with Alzheimer's disease (AD) recruited in a European observational study of AD. METHODS: 117 mild to moderate AD patients from 5 European centers (Amsterdam, The Netherlands; Brescia and Genova, Italy; Mannheim, Germany; Pamplona, Spain) had magnetic resonance imaging scans performed as part of the routine diagnostic examination. MTA was assessed with the visual Scheltens scale. RESULTS: AD patients from Brescia, Genova, Pamplona, and Mannheim had a mean 32% prevalence of no or borderline MTA vs. 62% of patients from Amsterdam (p = 0.002 for the difference between Amsterdam and all the other centers). The peculiar distribution of MTA in the Amsterdam patients may be attributable to younger age (70.7 +/- 8.4 vs. 75.3 +/- 6.8 years, p = 0.002), milder dementia severity (score 0.5 on the clinical dementia rating scale: 52 vs. 23%, p = 0.003), and less frequent depression (14 vs. 49%, p < 0.0005 in Amsterdam vs. all the other centers, respectively). CONCLUSION: Patients with probable AD recruited in different centers of Europe generally have similar MTA distribution, even if peculiar demographic and clinical findings might explain occasional differences. These results have implications for clinical trials in AD with biological markers as outcome measures.