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Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD). Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts. Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157). Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]). Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.

Background and purpose Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome, defined by a distinctive clinical-radiological profile, with Alzheimer's disease (AD) pathology accounting for the majority of cases. The aim of this report was to present the case of a patient with impairment of visual and constructional abilities as initial manifestations. Method The patient underwent a multidimensional assessment, including neuropsychological evaluation, structural and functional imaging and genetic screening. Results Neurological and neuropsychological assessment showed an impairment of constructive and visuo-spatial skills, associated with dyscalculia, simultanagnosia, optic ataxia and oculomotor apraxia. In accordance with the latest consensus criteria, a diagnosis of PCA was made. Consistent with the clinical findings, structural and functional imaging showed a peculiar pattern of atrophy with primary involvement of right parieto-occipital cortices, whereas cerebrospinal fluid biochemical analysis did not reveal a profile compatible with AD pathology. Genetic screening identified a known pathogenic GRN mutation. Conclusion We present a case of PCA in a GRN mutation carrier in whom a concomitant AD pathological process was excluded. Consequently, although lacking histological data, our case suggests GRN-related pathology causative of PCA. Through this report we provide further evidence for a new neurodegenerative pathway leading to PCA, extending the clinical spectrum of GRN-associated phenotypes.

Aberrations of large-scale brain networks are found in the majority of neurodegenerative disorders. The brain connectivity alterations underlying dementia with Lewy bodies (DLB) remain, however, still elusive, with contrasting results possibly due to the pathological and clinical heterogeneity characterizing this disorder. Here, we provide a molecular assessment of brain network alterations, based on cerebral metabolic measurements as proxies of synaptic activity and density, in a large cohort of DLB patients (N = 72). We applied a seed-based interregional correlation analysis approach (p < .01, false discovery rate corrected) to evaluate large-scale resting-state networks' integrity and their interactions. We found both local and long-distance metabolic connectivity alterations, affecting the posterior cortical networks, that is, primary visual and the posterior default mode network, as well as the limbic and attention networks, suggesting a widespread derangement of the brain connectome. Notably, patients with the lowest visual and attention cognitive scores showed the most severe connectivity derangement in regions of the primary visual network. In addition, network-level alterations were differentially associated with the core clinical manifestations, namely, hallucinations with more severe metabolic dysfunction of the attention and visual networks, and rapid eye movement sleep behavior disorder with alterations of connectivity of attention and subcortical networks. These multiple network-level vulnerabilities may modulate the core clinical and cognitive features of DLB and suggest that DLB should be considered as a complex multinetwork disorder.

Background and purpose Whether the reported association between migraine with aura (MA) and cardioembolic stroke may be explained by a higher rate of atrial fibrillation (AF) or by other potential cardiac sources of cerebral embolism remains to be determined.Methods In the setting of a single centre cohort study of consecutive patients with acute brain ischaemia stratified by migraine status, the association between AF as well as patent foramen ovale (PFO) and migraine was explored.Results In all, 1738 patients (1017 [58.5%] men, mean age 67.9 +/- 14.9 years) qualified for the analysis. Aging was inversely associated with migraine, whilst women had a >3-fold increased disease risk (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.58-5.66). No association between AF and history of migraine or its pathogenic subtypes was detected. Conversely, migraine was associated with PFO, both in the entire cohort (OR 1.84, 95% CI 1.07-3.16) and in patients aged

Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α-synuclein (α-syn), are neuropathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α-syn and modulates α-syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III. The in situ proximity ligation assay revealed the accumulation of numerous proteinase K-resistant neuropathological inclusions that contained both α-syn and syn III in tight association in the brain of affected subjects. Most strikingly, syn III was identified as a component of α-syn-positive fibrils in LB-enriched protein extracts from PD brains. Finally, a positive correlation between syn III and α-syn levels was detected in the caudate putamen of PD subjects. Collectively, these findings indicate that syn III is a crucial α-syn interactant and a key component of LB fibrils in the brain of patients affected by PD.

Objective Spinocerebellar ataxia 38 (SCA38) is caused by mutations in the ELOVL5 gene, which encodes an elongase involved in the synthesis of polyunsaturated fatty acids, including docosahexaenoic acid (DHA). As a consequence, DHA is significantly reduced in the serum of SCA38 subjects. In the present study, we evaluated the safety of DHA supplementation, its efficacy for clinical symptoms, and changes of brain functional imaging in SCA38 patients. Methods We enrolled 10 SCA38 patients, and carried out a double-blind randomized placebo-controlled study for 16 weeks, followed by an open-label study with overall 40-week DHA treatment. At baseline and at follow-up visit, patients underwent standardized clinical assessment, brain 18-fluorodeoxyglucose positron emission tomography, electroneurography, and ELOVL5 expression analysis. Results After 16 weeks, we showed a significant pre-post clinical improvement in the DHA group versus placebo, using the Scale for the Assessment and Rating of Ataxia (SARA; mean difference [MD] = +2.70, 95% confidence interval [CI] = +0.13 to + 5.27, p = 0.042). At 40-week treatment, clinical improvement was found significant by both SARA (MD = +2.2, 95% CI = +0.93 to + 3.46, p = 0.008) and International Cooperative Ataxia Rating Scale (MD = +3.8, 95% CI = +1.39 to + 6.41, p = 0.02) scores; clinical data were corroborated by significant improvement of cerebellar hypometabolism (statistical parametric mapping analyses, false discovery rate corrected). We also showed a decreased expression of ELOVL5 in patients' blood at 40 weeks as compared to baseline. No side effect was recorded. Interpretation DHA supplementation is a safe and effective treatment for SCA38, showing an improvement of clinical symptoms and cerebellar hypometabolism. Ann Neurol 2017;82:615-621.

Purpose: To compare registration strategies to align arterial spin labeling (ASL) with 3D T1-weighted (T1w) images, with the goal of reducing the between-subject variability of cerebral blood flow (CBF) images. Materials and Methods: Multi-center 3T ASL data were collected at eight sites with four different sequences in the multi-center GENetic Frontotemporal dementia Initiative (GENFI) study. In a total of 48 healthy controls, we compared the following image registration options: (I) which images to use for registration (perfusion-weighted images [PWI] to the segmented gray matter (GM) probability map (pGM) (CBF-pGM) or M0 to T1w (M0-T1w); (II) which transformation to use (rigid-body or non-rigid); and (III) whether to mask or not (no masking, M0-based FMRIB software library Brain Extraction Tool [BET] masking). In addition to visual comparison, we quantified image similarity using the Pearson correlation coefficient (CC), and used the Mann-Whitney U rank sum test. Results: CBF-pGM outperformed M0-T1w (CC improvement 47.2% ± 22.0%; P < 0.001), and the non-rigid transformation outperformed rigid-body (20.6% ± 5.3%; P < 0.001). Masking only improved the M0-T1w rigid-body registration (14.5% ± 15.5%; P = 0.007). Conclusion: The choice of image registration strategy impacts ASL group analyses. The non-rigid transformation is promising but requires validation. CBF-pGM rigid-body registration without masking can be used as a default strategy. In patients with expansive perfusion deficits, M0-T1w may outperform CBF-pGM in sequences with high effective spatial resolution. BET-masking only improves M0-T1w registration when the M0 image has sufficient contrast. Level of Evidence: 1. Technical Efficacy: Stage 1. J. Magn. Reson. Imaging 2018;47:131–140.

Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long-term potentiation-like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short-interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal-dominant FTD. Ann Neurol 2016;80:472-476.

Background DYT1 mutation is characterized by focal to generalized dystonia and incomplete penetrance. To explore the complex perturbations in the different neural networks and the mutual interactions among them, we studied symptomatic and asymptomatic DTY1 mutation carriers by resting-state functional MRI. Methods A total of 7 symptomatic DYT1, 10 asymptomatic DYT1, and 26 healthy controls were considered. Resting-state functional MRI (Oxford Centre for Functional MRI of the Brain) [FMRIB] Software Library) (FSL) MELODIC, dual regression, (as a toolbox of FSL, with Nets is referred to “networks”) (FSLNets) (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FSLNets) was performed on 9 resting-state neural networks. Results DYT1 mutation signature (symptomatic DYT1 and asymptomatic DYT1) was characterized by increased connectivity in the dorsal attention network and in the left fronto-parietal network. Functional correlates of symptomatic DYT1 patients (symptomatic DYT1 vs healthy controls) showed increased connectivity in the sensorimotor network. Discussion This study argues that DYT1 dystonia is a network disorder, with crucial nodes in sensory-motor integration of posterior parietal structures. A better characterization of cortical networks involved in dystonia is crucial for possible neurophysiological therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society

Background Parkinson's disease (PD) is characterized by both motor and cognitive deficits. In PD, physical exercise has been found to improve physical functioning. Recent studies demonstrated that repeated sessions of transcranial direct current stimulation led to an increased performance in cognitive and motor tasks in patients with PD. Objectives The present study investigated the effects of anodal transcranial direct current stimulation applied over the dorsolateral prefrontal cortex and combined with physical therapy in PD patients. Methods A total of 20 patients with PD were assigned to 1 of 2 study groups: group 1, anodal transcranial direct current stimulation plus physical therapy (n = 10) or group 2, placebo transcranial direct current stimulation plus physical therapy (n = 10). The 2 weeks of treatment consisted of daily direct current stimulation application for 25 minutes during physical therapy. Long-term effects of treatment were evaluated on clinical, neuropsychological, and motor task performance at 3-month follow-up. Results An improvement in motor abilities and a reduction of depressive symptoms were observed in both groups after the end of treatment and at 3-month follow-up. The Parkinson's Disease Cognitive Rating Scale and verbal fluency test performances increased only in the anodal direct current stimulation group with a stable effect at follow-up. Conclusions The application of anodal transcranial direct current stimulation may be a relevant tool to improve cognitive abilities in PD and might be a novel therapeutic strategy for PD patients with mild cognitive impairment. © 2016 International Parkinson and Movement Disorder Society

Background and Objective Numerous studies have highlighted the possibility of modulating the excitability of cerebellar circuits using transcranial direct current stimulation. The present study investigated whether a single session of cerebellar anodal transcranial direct current stimulation could improve symptoms in patients with ataxia. Methods Nineteen patients with ataxia underwent a clinical and functional evaluation pre- and post-double-blind, randomized, sham, or anodal transcranial direct current stimulation. Results There was a significant interaction between treatment and time on the Scale for the Assessment and Rating of Ataxia, on the International Cooperative Ataxia Rating Scale, on the 9-Hole Peg Test, and on the 8-Meter Walking Time (P

The limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous neuromuscular disorders caused by specific protein defects in muscle fibres and characterised by predominant weakness and wasting in proximal limb and axial muscles. Most of these diseases present with wide clinical heterogeneity and the limb-girdle phenotype should be regarded as one of the possible phenotypic expressions of a specific protein defect. Therefore, a precise clinical evaluation is often difficult, and an appropriate diagnostic approach using clinical, pathological, biochemical and genetic resources is essential to achieve the correct diagnosis. The current classification of LGMDs is based on inheritance pattern. Dominant forms are classified as type 1 (LGMD1), whereas the recessive forms are classified as type 2 (LGMD2). A progressive alphabetical letter identifies the different involved genes and indicates the order of identification. This review reports a comprehensive update on the genetic bases and the main clinical aspects of these groups of diseases according to protein defect and transmission modality. Key Concepts The limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of hereditary neuromuscular disorders caused by specific protein defects in muscle fibres and characterised by predominant weakness and wasting in proximal limb and axial muscles. The current classification of LGMDs is based on inheritance pattern. Dominant forms are classified as type 1 (LGMD1), whereas the recessive forms are classified as type 2 (LGMD2). A progressive alphabetical letter identifies the different involved genes and indicates the order of identification. LGMDs are diseases having wide inter- and intra-familial phenotypic heterogeneity and therefore the limb-girdle phenotype is often the only one of the possible phenotypic expressions of a specific protein defect. Four recessive LGMDs are caused by mutations in the genes encoding the four members of the skeletal muscle sarcoglycan complex which is a part of the large macromolecular complex of proteins named the dystrophin-associated protein complex (DAPC) which is thought to have structural functions in providing membrane stability, maintaining the integrity of sarcolemma and in ensuring transduction during muscle contraction. Eight genes have been found to be responsible for an LGMD-dystroglycanopathy until now. Mutations in these genes reduce dystroglycan glycosylation and cause different phenotypes ranging from mild to dramatic conditions. Limb-girdle muscular dystrophies should to be considered the mildest expression of the phenotypic spectrum of dystroglycanopathies. Keywords: LGMD; autosomal-dominant limb-girdle muscular dystrophy; autosomal-recessive limb-girdle muscular dystrophy; muscle biopsy; myopathy

Objective To assess whether physical activity is a risk factor for amyotrophic lateral sclerosis (ALS). Methods From February 2008 to April 2012, 652 patients with ALS from European population-based registries (France, Ireland, Italy, United Kingdom, Serbia) and 1,166 population controls (matched for age, sex, and residency) were assessed. Upon direct interview, data were collected on occupation and history of sport and leisure activities, physical activity, and accidental injuries. Physical exercise was defined as having spent time doing activities that caused an individual to breath hard at least once per month and was coded as none, job-related, and/or sport-related. Sport-related and work-related physical exercise were quantified using metabolic equivalents (METs). Risks were calculated using conditional logistic regression models (adjusting for age, country, trauma, and job-related physical activity) and expressed as odds ratios (ORs) and adjusted ORs (Adj ORs) with 95% confidence intervals (CIs). Results Overall physical activity was associated with reduced odds of having ALS (Adj OR = 0.65, 95% CI = 0.48–0.89) as were work-related physical activity (Adj OR = 0.56, 95% CI = 0.36–0.87) and organized sports (Adj OR = 0.49, 95% CI = 0.32–0.75). An inverse correlation was observed between ALS, the duration of physical activity (p = 0.0041), and the cumulative MET scores, which became significant for the highest exposure (Adj OR = 0.34, 95% CI = 0.21–0.54). An inverse correlation between ALS and sport was found in women but not in men, and in subjects with repeated traumatic events. Interpretation Physical activity is not a risk factor for ALS and may eventually be protective against the disease. ANN NEUROL 2014;75:708–716

© 2016 The Authors. **Human Mutation published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS.

Background and purpose: Progressive non-fluent aphasia (PNFA) is a neurodegenerative disorder that is characterized by non-fluent speech with naming impairment and grammatical errors. It has been recently demonstrated that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral pre-frontal cortex (DLPFC) improves action naming in healthy subjects and in subjects with Alzheimers disease. Purpose: To investigate whether the modulation of DLPFC circuits by rTMS modifies naming performance in patients with PNFA. Methods: Ten patients with a diagnosis of PNFA were enrolled. High-frequency rTMS was applied to the left and right DLPFC and the sham (i.e. placebo) condition during object and action naming. A subgroup of patients with semantic dementia was enrolled as a comparison group. Results: A repeated-measure analysis of variance with stimulus site (sham, left and right rTMS) showed significant effects. Action-naming performances during stimulation of both the left and right DLPFC were better than during placebo stimulation. No facilitating effect of rTMS to the DLPFC on object naming was observed. In patients with a diagnosis of semantic dementia, no effect of stimulation was reported. Conclusions: Our study demonstrated that rTMS improved action naming in subjects with PNFA, possibly due to the modulation of DLPFC pathways and a facilitation effect on lexical retrieval processes. Future studies on the potential of a rehabilitative protocol using rTMS applied to the DLPFC in this orphan disorder are required.

Objective To examine the usefulness of specific neurocognitive tests for predicting the crash involvement in ultra-octogenarian population. Methods A total of 800 subjects (mean age 82.4 + 3.1 years) underwent a battery of neuropsychological tests. Global intellectual functioning was assessed using the Mini Mental State Examination, mental flexibility and information processing speed were assessed using the Trail Making Test parts A and B (TMT-A and TMT-B), long-term memory was evaluated with the short story, and visuo-spatial skills were tested with Clock Drawing Test. One year after this evaluation, 343 (43%) participants have been interviewed by a telephone call to know if they were currently driving and if they had a car crash during this period. Results Two hundred ninety-seven subjects had their driving license renewed and completed the follow-up 1 year after. Data shows that less than 11% of this group had a car crash during the first year of observation (Crash Involved). Older subjects involved in a car crash showed significant worse performances on TMT-B (TMT-B pathological Crash Involved vs. Noncrash Involved 47% vs. 27%; p = 0.02) and on short story (short story pathological Crash Involved vs. Noncrash Involved 19% vs. 5%; p = 0.02). Conclusions Trail Making test B and short story have been demonstrated to provide a predictive value of driving performance of older people. Therefore, we suggest that a simple and standardized battery of neuropsychological tests, lasting about 30 min and administered by an experienced staff, is a good diagnostic instrument for risk prevention of driving activity of older drivers. Copyright © 2012 John Wiley & Sons, Ltd.

Although alpha-synuclein is the main constituent of Lewy bodies, cerebrospinal fluid determination on its own does not seem fundamental for the diagnosis of synucleinopathies. We evaluated whether the combination of classical biomarkers, Aβ(1-42) , total tau, phosphorylated tau, and α-synuclein can improve discrimination of Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, and frontotemporal dementia. Aβ(1-42) , total tau, phosphorylated tau, and α-synuclein were measured in a series of patients with Parkinson's disease (n = 38), dementia with Lewy bodies (n = 32), Alzheimer's disease (n = 48), frontotemporal dementia (n = 31), and age-matched control patients with other neurological diseases (n = 32). Mean α-synuclein levels in cerebrospinal fluid were significantly lower in the pathological groups than in cognitively healthy subjects. An inverse correlation of α-synuclein with total tau (r = -0.196, P < .01) was observed. In the group of patients with Parkinson's disease, Aβ(1-42) , total tau, and phosphorylated tau values were similar to controls, whereas total tau/α-synuclein and phosphorylated tau/α-synuclein ratios showed the lowest values. Cerebrospinal fluid α-synuclein alone did not provide relevant information for Parkinson's disease diagnosis, showing low specificity (area under the curve, 0.662; sensitivity, 94%; specificity, 25%). Instead, a better performance was obtained with the total tau/α-syn ratio (area under the curve, 0.765; sensitivity, 89%; specificity, 61%). Combined determination of α-synuclein and classical biomarkers in cerebrospinal fluid shows differential patterns in neurodegenerative disorders. In particular, total tau/α-synuclein and phosphorylated tau/α-synuclein ratios can contribute to the discrimination of Parkinson's disease. © 2011 Movement Disorder Society.

Background and purpose: Frontotemporal dementia (FTD) is the second most common neurodegenerative dementia in the young age after Alzheimer disease. Recent improvement in diagnostic assessment suggests that it is more common than previously, although with a great heterogeneity in clinical presentation. The different clinical patterns related to age of disease onset in behavioural variant FTD (bvFTD) have been fairly studied. Aim of the study was to evaluate whether age at disease onset modulate the heterogeneity of either cognitive impairment or behavioural disturbances in patients affected by bvFTD. Methods: One hundred and thirty-four patients with bvFTD entered the study. Age at onset and demographic characteristics were carefully recorded. Each patient underwent a wide neuropsychological and behavioural standardized assessment, as well as a brain SPECT perfusion imaging study. Results: Behavioural variant FTD were subdivided into four groups according to the age at onset. The four quartile groups did not differ for demographic characteristics and family history for dementia. Global cognitive impairment as well as analysis of the different cognitive domains and behavioural patterns were comparable. Conclusions: These findings provide evidence that the clinical heterogeneity of bvFTD is not explained by age at disease onset. Further studies are needed.

Background Mild Cognitive Impairment defines a transitional stage between normal ageing and dementia, and reflects the clinical situation where a person has memory complaints and objective evidence of cognitive impairment but no evidence of dementia. To plan the care of patients with MCI, it is important to predict as accurately as possible potential risk factors modulating the conversion to AD. Aim To investigate the risk factors associated of conversion to dementia of Alzheimer type (AD) for subjects with amnestic Mild Cognitive Impairment (aMCI). Methods and Materials One hundred nineteen subjects consecutively recruited who met the operational criteria for aMCI (with or without deficits in other cognitive domains). They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after 1 year. Diagnosis for dementia was based on a deficit in two or more cognitive domains severe enough to affect the participant functional abilities. Subjects converted to AD over time were classified as Demented; subjects that remained unchanged, or became cognitively normal during follow-up, were defined as Stable. Results Demented MCI (N = 40; 33.6%) were older (mean age 73.5 ± 8.5 vs. 69.2 ± 7.0; p = 0.006) when compared to Stable (N = 79; 66.4) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (mean score 10.7 ± 3.9 vs 6.7 ± 3.4; p = .000) and by MMSE (mean score 26.1 ± 1.9 vs. 27.3 ± 1.8; p = 0.002). Demented were similarly compromised in basic activities of daily living (BADL mean 0.2 ± 0.4 vs 0.1 ± 0.3 functions lost; p = NS) but more compromised on instrumental daily functions (IADL mean 0.7 ± 0.8 vs. 0.1 ± 0.5 functions lost; p = 0.001). The presence of white matter lesions (WML) on CT or MRI was more pronounced in Demented group (p = 0.02). After 1 year; Demented worsened on phonemic verbal fluency (PFL) (p = 0.009), Raven's coloured matrices (p = 0.003), Trail Making test A and B (p = 0.008 and p = 0.007 respectively) and in Instrumental Activities of Daily Living (IADL) (p =0 .000) respect to Stable. Logistic regression analysis revealed that ADAS-Cog basal score, Trail Making B, IADL but not memory deterioration were significantly associated to the conversion to AD. Conclusions In subjects with aMCI poor global cognitive performance at baseline, the worsening on executive functions and on functional status but not the worsening on memory functions are independently associated with the conversion to dementia of Alzheimer type at 1 year, follow-up. Copyright © 2007 John Wiley & Sons, Ltd.

Transient global amnesia (TGA) is a well-defined clinical syndrome of unknown etiology, which often occurs once in life. Several mechanisms have been proposed but only trigger events have been clearly associated with the attack such as physical exertion, emotional stress, sexual intercourse or immersion in cold water. According to our knowledge, this is the first study, which associates trigger events and TGA recurrency. The aim of this retrospective study was to evaluate the risk factors which contribute to TGA recurrency. TGA patients consecutively admitted, performed clinical and neurological evaluation, electroencephalogram and structural brain imaging scan. TGA-trigger events were evaluated and comorbidities were carefully recorded. The risk factor sum was calculated as the sum of the considered triggers. Eighty-five TGA patients were grouped according to the presence of single TGA (n = 73) or two episodes of TGA (n = 12). The 14.11% of patients experienced two episodes. A logistic regression analysis showed that the more increased number of TGA the more number of trigger events (P < 0.11; chi2 = 6.38; beta = -3.29). These observations claim that TGA may be considered a complex epiphenomenon, and the sum of the trigger factors can be responsible for recurring of this almost unique-in-life event.

Objectives: To investigate the effect of cardiovascular changes (i.e., QT interval, QT dispersion (QTD), heart rate variability (HRV), and other cardiovascular measures) in subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Design: Each subject underwent clinical and cognitive examination, a structural brain imaging study, echocardioDoppler, electrocardiogram (ECG), HRV analysis using 24-hour ECG monitoring, and 24-hour blood pressure monitoring. Setting: Community population-based sample of patients admitted to an AD center for investigation of cognitive disturbances. Participants: Thirty-three subjects with AD, 39 subjects with MCI, and 29 cognitive healthy subjects (controls) matched for demographic characteristics, hypertensive condition, smoking habits, and laboratory parameters were enrolled consecutively. Measurements: Clinical and cognitive examination, structural brain imaging study, echocardioDoppler, ECG, HRV analysis using 24-hour ECG monitoring, and 24-hour blood pressure monitoring. Results: QTD and QT corrected dispersion mean values were significantly higher in patients with AD than in patients with MCI and controls and higher in patients with MCI than in controls. HRV time and domain parameters were lower in patients with AD than in patients with MCI and controls. No difference in other cardiovascular measures was found. QTD and HRV were found to be significantly correlated with the degree of cognitive impairment. Conclusion: These findings support the presence of a peculiar neuroanatomic dysfunction in patients with AD and MCI that parallels the disease progression. These noninvasive parameters might prove to be powerful predictive tools in the worsening of cognitive function and mortality risk.