Differential Diagnosis of Alzheimer Disease vs. Mild Cognitive Impairment Based on Left Temporal Lateral Lobe Hypomethabolism on 18F-FDG PET/CT and Automated Classifiers.

PURPOSE: We evaluate the ability of Artificial Intelligence with automatic classification methods applied to semi-quantitative data from brain 18F-FDG PET/CT to improve the differential diagnosis between Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). PROCEDURES: We retrospectively analyzed a total of 150 consecutive patients who underwent diagnostic evaluation for suspected AD (n = 67) or MCI (n = 83). All patients received brain 18F-FDG PET/CT according to the international guidelines, and images were analyzed both Qualitatively (QL) and Quantitatively (QN), the latter by a fully automated post-processing software that produced a z score metabolic map of 25 anatomically different cortical regions. A subset of n = 122 cases with a confirmed diagnosis of AD (n = 53) or MDI (n = 69) by 18-24-month clinical follow-up was finally included in the study. Univariate analysis and three automated classification models (classification tree -ClT-, ridge classifier -RC- and linear Support Vector Machine -lSVM-) were considered to estimate the ability of the z scores to discriminate between AD and MCI cases in. RESULTS: The univariate analysis returned 14 areas where the z scores were significantly different between AD and MCI groups, and the classification accuracy ranged between 74.59% and 76.23%, with ClT and RC providing the best results. The best classification strategy consisted of one single split with a cut-off value of ≈ -2.0 on the z score from temporal lateral left area: cases below this threshold were classified as AD and those above the threshold as MCI. CONCLUSIONS: Our findings confirm the usefulness of brain 18F-FDG PET/CT QL and QN analyses in differentiating AD from MCI. Moreover, the combined use of automated classifications models can improve the diagnostic process since its use allows identification of a specific hypometabolic area involved in AD cases in respect to MCI. This data improves the traditional 18F-FDG PET/CT image interpretation and the diagnostic assessment of cognitive disorders.

Accuracy of the clinical diagnosis of dementia with Lewy bodies (DLB) among the Italian Dementia Centers: a study by the Italian DLB study group (DLB-SINdem).

INTRODUCTION: Dementia with Lewy bodies (DLB) may represent a diagnostic challenge, since its clinical picture overlaps with other dementia. Two toolkits have been developed to aid the clinician to diagnose DLB: the Lewy Body Composite Risk Score (LBCRS) and the Assessment Toolkit for DLB (AT-DLB). We aim to evaluate the reliability of these two questionnaires, and their ability to enhance the interpretation of the international consensus diagnostic criteria. METHODS: LBCRS and AT-DLB were distributed to 135 Italian Neurological Centers for Cognitive Decline and Dementia (CDCDs), with the indication to administer them to all patients with dementia referred within the subsequent 3 months. We asked to subsequently apply consensus criteria for DLB diagnosis, to validate the diagnostic accuracy of the two toolkits. RESULTS: A total of 23 Centers joined the study; 1854 patients were enrolled. We found a prevalence of possible or probable DLB of 13% each (26% total), according to the consensus criteria. LBCRS toolkit showed good reliability, with a Cronbach alpha of 0.77, stable even after removing variables from the construct. AT-DLB toolkit Cronbach alpha was 0.52 and, after the subtraction of the "cognitive fluctuation" criterion, was only 0.31. Accuracy, sensitivity, and specificity were higher for LBCRS vs. AT-DLB. However, when simultaneously considered in the logistic models, AT-DLB showed a better performance (p < 0.001). Overall, the concordance between LBCRS positive and AT-DLB possible/probable was of 78.02% CONCLUSIONS: In a clinical setting, the LBCRS and AT-DLB questionnaires have good accuracy for DLB diagnosis.

Validity of cerebrovascular ICD-9-CM codes in healthcare administrative databases. The Umbria Data-Value Project.

BACKGROUND: Validation of administrative databases for cerebrovascular diseases is crucial for epidemiological, outcome, and health services research. The aim of this study was to validate ICD-9 codes for hemorrhagic or ischemic stroke in administrative databases, to use them for a comprehensive assessment of the burden of disease in terms of major outcomes, such as mortality, hospital readmissions, and use of healthcare resources. METHODS: We considered the hospital discharge abstract database of the Umbria Region (890,000 residents). Source population was represented by patients aged >18 discharged from hospital with a diagnosis of hemorrhagic or ischemic stroke between 2012 and 2014 using ICD-9-CM codes in primary position. We randomly selected and reviewed medical charts of cases and non-cases from hospitals. For case ascertainment we considered symptoms and instrumental tests reported in the medical charts. Diagnostic accuracy measures were computed using 2x2 tables. RESULTS: We reviewed 767 medical charts for cases and 78 charts for non-cases. Diagnostic accuracy measures were: subarachnoid hemorrhage: sensitivity (SE) 100% (95% CI: 97%-100%), specificity (SP) 96% (90-99), positive predictive value (PPV) 98% (93-100), negative predictive value (NPV) 100% (95-100); intracerebral hemorrhage: SE 100% (97-100), SP 98% (91-100), PPV 98% (94-100), NPV 100% (95-100); other and unspecified intracranial hemorrhage: SE 100% (97-100), SP 96% (90-99), PPV 98% (93-100), NPV 100% (95-100); ischemic stroke due to occlusion and stenosis of precerebral arteries: SE 99% (94-100), SP 66 (57-75), PPV 70% (61-77), NPV 99% (93-100); occlusion of cerebral arteries: SE 100% (97-100), SP 87% (78-93), PPV 91% (84-95), NPV 100% (95-100); acute, but ill-defined, cerebrovascular disease: SE 100% (97-100), SP 78% (69-86), PPV % 83 (75-89), NPV 100% (95-100). CONCLUSIONS: Case ascertainment for both ischemic and hemorrhagic stroke showed good or high levels of accuracy within the regional healthcare databases in Umbria. This database can confidently be employed for epidemiological, outcome, and health services research related to any type of stroke.

Italian revised memory and behavior problems checklist (It-RMBPC): validation and psychometric properties in Alzheimer's disease caregivers.

Behavioral and psychiatric symptoms (BPSD), common in persons with Alzheimer's disease (AD), are known to be associated with caregiver burdening. Therefore, early recognition of BPSD is necessary to protect these caregivers. The aim of this validation study was to test the internal consistency, test-retest reliability and concurrent validity of an Italian translation of the revised memory and behavior problems checklist (RMBPC), as it demonstrated high plasticity in timely measuring the day-to-day BPSD changes that challenge caregivers. A cohort of 355 dyads composed of AD subjects and their principal caregivers were assessed with the Italian version of RMPBC capitalizing on the information provided by the latter ones. The results were compared with the ones from other predictors (i.e., the Zarit Burben Interview, the Hospital Anxiety and Depression Scale, the EurQuality of Life, the neuropsychiatric symptoms). The validity and stability of the It-RMBPC resulted being solid and concurrent reliability resulted having higher correlations with principal caregiver anxiety level. Future studies on the role of BPSD in fostering anxiety in AD principal caregivers are merited.

Role of Artificial Intelligence Techniques (Automatic Classifiers) in Molecular Imaging Modalities in Neurodegenerative Diseases.

Artificial Intelligence (AI) is a very active Computer Science research field aiming to develop systems that mimic human intelligence and is helpful in many human activities, including Medicine. In this review we presented some examples of the exploiting of AI techniques, in particular automatic classifiers such as Artificial Neural Network (ANN), Support Vector Machine (SVM), Classification Tree (ClT) and ensemble methods like Random Forest (RF), able to analyze findings obtained by positron emission tomography (PET) or single-photon emission tomography (SPECT) scans of patients with Neurodegenerative Diseases, in particular Alzheimer's Disease. We also focused our attention on techniques applied in order to preprocess data and reduce their dimensionality via feature selection or projection in a more representative domain (Principal Component Analysis - PCA - or Partial Least Squares - PLS - are examples of such methods); this is a crucial step while dealing with medical data, since it is necessary to compress patient information and retain only the most useful in order to discriminate subjects into normal and pathological classes. Main literature papers on the application of these techniques to classify patients with neurodegenerative disease extracting data from molecular imaging modalities are reported, showing that the increasing development of computer aided diagnosis systems is very promising to contribute to the diagnostic process.

Longitudinal gray matter contraction in three variants of primary progressive aphasia: A tenser-based morphometry study.

The present study investigated the pattern of longitudinal changes in cognition and anatomy in three variants of primary progressive aphasia (PPA). Eight patients with the non-fluent variant of PPA (nfvPPA), 13 patients with the semantic variant (svPPA), seven patients with the logopenic variant (lvPPA), and 29 age-matched, neurologically healthy controls were included in the study. All participants underwent longitudinal MRI, neuropsychological and language testing at baseline and at a 1-year follow-up. Tenser-based morphometry (TBM) was applied to T1-weighted MRI images in order to map the progression of gray and white matter atrophy over a 1-year period. Results showed that each patient group was characterized by a specific pattern of cognitive and anatomical changes. Specifically, nfvPPA patients showed gray matter atrophy progression in the left frontal and subcortical areas as well as a decline in motor speech and executive functions; svPPA patients presented atrophy progression in the medial and lateral temporal lobe and decline in semantic memory abilities; and lvPPA patients showed atrophy progression in lateral/posterior temporal and medial parietal regions with a decline in memory, sentence repetition and calculations. In addition, in all three variants, the white matter fibers underlying the abovementioned cortical areas underwent significant volume contraction over a 1-year period. Overall, these results indicate that the three PPA variants present distinct patterns of neuroanatomical contraction, which reflect their clinical and cognitive progression.

Memory dysfunction.

Memory is the cognitive ability that allows to acquire, store and recall information; its dysfunction is called amnesia and can be a presentation of unilateral ischemic stroke in the territory of the posterior cerebral and anterior choroidal artery as well as subarachnoid hemorrhage.

Thalamic infarcts and hemorrhages.

The anatomy and supply of thalamic arteries are briefly described here. Thalamic infarcts and small-size hemorrhages are classified according to their sites: (1) posterolateral, (2) anterolateral, (3) medial, and (4) dorsal. (1) Posterolateral hemorrhages or lateral thalamic infarcts are usually characterized by severe motor impairment and sensory loss. Transient reduced consciousness, vertical-gaze abnormalities, and small fixed pupils may be evidenced. (2) Patients with anterolateral hemorrhages or tuberothalamic artery infarcts present frontal-type neuropsychological symptoms associated with mild hemiparesis and hemihypesthesia. (3) Medially located hemorrhages or paramedian artery infarcts have decreased levels of consciousness, vertical- and horizontal-gaze abnormalities, amnesia, and abulia. (4) Dorsal hemorrhages or posterior choroidal artery infarcts present with minimal transient hemiparesis and hemihypesthesia; apraxia, aphasia, and amnesia have also been described.

Gene-drug interaction in stroke.

Stroke is the third cause of mortality and one of most frequent causes of long-term neurological disability, as well as a complex disease that results from the interaction of environmental and genetic factors. The focus on genetics has produced a large number of studies with the objective of revealing the genetic basis of cerebrovascular diseases. Furthermore, pharmacogenetic research has investigated the relation between genetic variability and drug effectiveness/toxicity. This review will examine the implications of pharmacogenetics of stroke; data on antihypertensives, statins, antiplatelets, anticoagulants, and recombinant tissue plasminogen activator will be illustrated. Several polymorphisms have been studied and some have been associated with positive drug-gene interaction on stroke, but the superiority of the genotype-guided approach over the clinical approach has not been proved yet; for this reason, it is not routinely recommended.

Secondary stroke prevention in women.

In a meta-analysis of results from 21 randomized trials comparing antiplatelet therapy with placebo in 18,270 patients with prior stroke or transient ischemic attack, antiplatelet therapy was associated with a 28% relative odds reduction in nonfatal strokes and a 16% reduction in fatal strokes, while another trial for secondary prevention with atorvastastin 80 mg showed a 16% risk reduction in time to first occurrence of stroke (adjusted hazard ratio: 0.84, 95% CI: 0.71-0.99). However, few studies have examined the sex differences regarding the efficacy of these treatments. Specifically, recent studies have reported higher rates of perioperative complications during endarterectomy in women. Nonetheless, to date, the data on the effects of carotid artery stenting in women, coming from diverse studies and meta-analyses, have been limited owing to the small number of female patients examined. Owing to this, the evidence of the benefit for women is unclear. Peculiar pathophysiological aspects of stroke, the higher stroke risk in some specific periods in life (e.g., pregnancy, puerperium and older age) and worse documented stroke outcome in women suggest that sex does matter in stroke management. Thus, future randomized controlled trials need to be sex-balanced, in order to better understand the efficacy of appropriate secondary stroke prevention therapy in women.

[Integrated local health services for Alzheimer's disease in Umbria (Italy)]. / Il Distretto affronta l'emergenza demenze: servizi integrati per l'Alzheimer.

To improve the quality of healthcare for patients affected by dementia (Alzheimer's and other types of dementia) and provide support to family caregivers, a health district in Umbria (Italy) has developed a network of social and health services integrated with third-sector and voluntary sector activities and has worked on addressing both the health and social needs of patients and their caregivers. In this article the authors describe the implemented activities which include educational activities, forming a self-help group for caregivers of Alzheimer patients, opening a counseling center and an outpatient clinic for Alzheimer's disease and cognitive disorders.

Performance in specific language tasks correlates with regional volume changes in progressive aphasia.

BACKGROUND: Patterns of language impairment have long been used clinically to localize brain damage in stroke patients. The same approach might be useful in the differential diagnosis of progressive aphasia owing to neurodegenerative disease. OBJECTIVE: To investigate whether scores on 4 widely used language tasks correlate with regional gray matter loss in 51 patients with progressive language impairment owing to neurodegenerative disease. METHOD: Scores in the Boston Naming Test and in the "repetition" "sequential commands" and the "language fluency," subtests of the Western Aphasia Battery were correlated with voxel-wise gray matter volumes using voxel-based morphometry. RESULTS: Significant positive correlations were found between each language task and regional brain volumes: (1) naming and the bilateral temporal lobes; (2) sentence repetition and the left posterior portion of the superior temporal gyrus; (3) sentence comprehension and the left dorsal middle and inferior frontal gyri; and (4) fluency of language production and the left ventral middle and inferior frontal gyri. DISCUSSION: Performance on specific language tasks corresponds to regional anatomic damage in aphasia owing to neurodegenerative disorders. These language tests might be useful in the differential diagnosis of primary progressive aphasia variants that have been previously associated with damage to corresponding anatomic regions.

Anatomical correlates of sentence comprehension and verbal working memory in neurodegenerative disease.

This study investigates whether sentence comprehension and nonsyntactic verbal working memory (vWM) are sustained by the same or by different neural systems. Scores in a sentence-picture matching task and in digits backward (DB) were correlated with magnetic resonance imaging voxelwise gray matter volumes using voxel-based morphometry in 58 patients with neurodegenerative diseases. Results showed that overall sentence comprehension scores, regardless of grammatical structure, correlated with gray matter volumes in the left temporoparietal region, whereas DB scores correlated with dorsolateral prefrontal and inferior parietal volumes. Comprehension of multiclausal relative sentences (type 3) significantly correlated with voxels in the dorsal portion of the left inferior and middle frontal gyri. When DB and multiclausal relative sentences were directly compared, they showed overlapping neural substrates in the dorsolateral left frontal region, supporting a single source of vWM for syntactic and nonsyntactic tasks. Within this large area of common involvement, a small portion of pars triangularis showed an independent effect of multiclausal sentences, whereas a region in the middle frontal gyrus showed greater correlation with DB. This study reconciles two opposing views, which hold that sentence comprehension and vWM rely on either the same or different anatomical resources.

An overview on Primary Progressive Aphasia and its variants.

We present a review of the literature on Primary Progressive Aphasia (PPA) together with the analysis of neuropschychological and neuroradiologic profiles of 42 PPA patients. Mesulam originally defined PPA as a progressive degenerative disorder characterized by isolated language impairment for at least two years. The most common variants of PPA are: 1) Progressive nonfluent aphasia (PNFA), 2) semantic dementia (SD), 3) logopenic progressive aphasia (LPA). PNFA is characterized by labored speech, agrammatism in production, and/or comprehension. In some cases the syndrome begins with isolated deficits in speech. SD patients typically present with loss of word and object meaning and surface dyslexia. LPA patients have word-finding difficulties, syntactically simple but accurate language output and impaired sentence comprehension. The neuropsychological data demonstrated that SD patients show the most characteristic pattern of impairment, while PNFA and LPA overlap within many cognitive domains. The neuroimaging analysis showed left perisylvian region involvement. A comprehensive cognitive, neuroimaging and pathological approach is necessary to identify the clinical and pathogenetic features of different PPA variants.

Clinical and neuropsychological features of corticobasal degeneration.

In this paper, we review the history, clinical, cognitive, imaging and neuropathological features of corticobasal degeneration (CBD). Additionally, we report new findings on the neuropsychological profile of 14 patients with CBD compared to 14 with Alzheimer's disease. Increasing awareness of this disorder has led to the realization that specific cognitive and imaging changes are common with CBD degeneration and that these changes help with clinical diagnosis.

Apraxia of speech: an overview.

Apraxia of speech (AOS) is a motor speech disorder that can occur in the absence of aphasia or dysarthria. AOS has been the subject of some controversy since the disorder was first named and described by Darley and his Mayo Clinic colleagues in the 1960s. A recent revival of interest in AOS is due in part to the fact that it is often the first symptom of neurodegenerative diseases, such as primary progressive aphasia and corticobasal degeneration. This article will provide a brief review of terminology associated with AOS, its clinical hallmarks and neuroanatomical correlates. Current models of motor programming will also be addressed as they relate to AOS and finally, typical treatment strategies used in rehabilitating the articulation and prosody deficits associated with AOS will be summarized.

A case of vertebrobasilar stroke during oxygen-ozone therapy.

Despite only sporadic observations, the use of medical oxygen-ozone therapy is a largely diffused treatment for lumbar disk herniation that has failed to respond to conservative management. Combined intradiscal and periganglionic injection of medical ozone and periganglionic injection of steroids are presumed to have a cumulative effect enhancing the overall outcome of treatment for pain caused by disk herniation. To our knowledge, this is the first reported case of stroke during such medical application. The patient had Anton's syndrome as a result of top of the basilar hypoperfusion.

Hyperhomocyst(e)inemia: a risk factor for cerebrovascular disease.

Many case-control and cohort studies have identified a strong, independent and dose-related association between moderate hyperhomocyst(e)inemia and atherosclerotic vascular disease, with respect to the pathogenetic link between hyperhomocyst(e)inemia and stroke, the possible role in inducing an endothelial wall damage deserves special attention. Some prospective cohort studies have failed to demonstrate a positive association between elevated homocyst(e)ine (Hcy) levels and stroke. Further studies are needed, in order to better characterize the association between Hcy concentrations and risk of stroke.