Optimal MoCA cutoffs for detecting biologically-defined patients with MCI and early dementia.

OBJECTIVE: In this phase II psychometric study on the Montreal cognitive assessment (MoCA), we tested the clinicometric properties of Italian norms for patients with mild cognitive impairment (PwMCI) and early dementia (PwD) and provided optimal cutoffs for diagnostic purposes. METHODS: Retrospective data collection was performed for consecutive patients with clinically and biologically defined MCI and early dementia. Forty-five patients (24 PwMCI and 21 PwD) and 25 healthy controls were included. Raw MoCA scores were adjusted according to the conventional 1-point correction (Nasreddine) and Italian norms (Conti, Santangelo, Aiello). The diagnostic properties of the original cutoff (< 26) and normative cutoffs, namely, the upper limits (uLs) of equivalent scores (ES) 1, 2, and 3, were evaluated. ROC curve analysis was performed to obtain optimal cutoffs. RESULTS: The original cutoff demonstrated high sensitivity (0.93 [95% CI 0.84-0.98]) but low specificity (0.44 [0.32-0.56]) in discriminating between patients and controls. Nominal normative cutoffs (ES0 uLs) showed excellent specificity (SP range = 0.96-1.00 [0.88-1.00]) but poor sensitivity (SE range = 0.09-0.24 [0.04-0.36]). The optimal cutoff for Nasreddine's method was 23.50 (SE = 0.82 [0.71-0.90]; SP = 0.72 [0.60-0.82]). Optimal cutoffs were 20.97, 22.85, and 22.29 (SE range = 0.69-0.73 [0.57-0.83], SP range = 0.88-0.92 [0.77-0.97]) for Conti's, Santangelo's, and Aiello's methods, respectively. CONCLUSION: Using the 1-point correction, combined with a cutoff of 23.50, might be useful in ambulatory settings with a large turnout. Our optimal cutoffs can offset the poor sensitivity of Italian cutoffs.

Alpha-synuclein seeds in olfactory mucosa and cerebrospinal fluid of patients with dementia with Lewy bodies.

In patients with suspected dementia with Lewy bodies, the detection of the disease-associated α-synuclein in easily accessible tissues amenable to be collected using minimally invasive procedures remains a major diagnostic challenge. This approach has the potential to take advantage of modern molecular assays for the diagnosis of α-synucleinopathy and, in turn, to optimize the recruitment and selection of patients in clinical trials, using drugs directed at counteracting α-synuclein aggregation. In this study, we explored the diagnostic accuracy of α-synuclein real-time quaking-induced conversion assay by testing olfactory mucosa and CSF in patients with a clinical diagnosis of probable (n = 32) or prodromal (n = 5) dementia with Lewy bodies or mixed degenerative dementia (dementia with Lewy bodies/Alzheimer's disease) (n = 6). Thirty-eight patients with non-α-synuclein-related neurodegenerative and non-neurodegenerative disorders, including Alzheimer's disease (n = 10), sporadic Creutzfeldt-Jakob disease (n = 10), progressive supranuclear palsy (n = 8), corticobasal syndrome (n = 1), fronto-temporal dementia (n = 3) and other neurological conditions (n = 6) were also included, as controls. All 81 patients underwent olfactory swabbing while CSF was obtained in 48 participants. At the initial blinded screening of olfactory mucosa samples, 38 out of 81 resulted positive while CSF was positive in 19 samples out of 48 analysed. After unblinding of the results, 27 positive olfactory mucosa were assigned to patients with probable dementia with Lewy bodies, five with prodromal dementia with Lewy bodies and three to patients with mixed dementia, as opposed to three out 38 controls. Corresponding results of CSF testing disclosed 10 out 10 positive samples in patients with probable dementia with Lewy bodies and six out of six with mixed dementia, in addition to three out of 32 for controls. The accuracy among results of real-time quaking-induced conversion assays and clinical diagnoses was 86.4% in the case of olfactory mucosa and 93.8% for CSF. For the first time, we showed that α-synuclein real-time quaking-induced conversion assay detects α-synuclein aggregates in olfactory mucosa of patients with dementia with Lewy bodies and with mixed dementia. Additionally, we provided preliminary evidence that the combined testing of olfactory mucosa and CSF raised the concordance with clinical diagnosis potentially to 100%. Our results suggest that nasal swabbing might be considered as a first-line screening procedure in patients with a diagnosis of suspected dementia with Lewy bodies followed by CSF analysis, as a confirmatory test, when the result in the olfactory mucosa is incongruent with the initial clinical diagnosis.

Using the ATN system as a guide for the neuropsychological assessment of Alzheimer's disease.

INTRODUCTION: Many studies have attempted to determine whether Alzheimer's disease (AD) in-vivo biomarkers can predict neuropsychological performance since pathophysiological changes precede cognitive changes by several years. Nonetheless, neuropsychological measures can also detect cognitive deterioration in cognitively normal individuals with AD-positive biomarkers. Recent studies have investigated whether cognitive measures can be used as a proxy for biomarkers. This is a crucial issue since biomarker analysis is expensive, invasive, and not yet widespread in clinical practice. However, these studies have so far considered only one or two classes of AD biomarkers. Here, we aim at preliminarily evaluating whether and which neuropsychological measures can discriminate individuals that have been classified according to the full scheme of biomarkers known as ATN system. This scheme groups biomarkers as a function of the three main AD-related pathologic processes they measure (i.e., ß-amyloidosis, tauopathy, and neurodegeneration) to provide an unbiased and descriptive definition of the Alzheimer's continuum. METHOD: Biomarkers and neuropsychological data from 78 patients (70.01 ± 9.15 years; 38 females) with suspected cognitive decline were extracted from a medical database. Participants' biomarker profiles were classified into the following ATN categories: normal AD biomarkers; Alzheimer's continuum; non-AD pathologic change. Data were analyzed using a Bayesian approach, to guarantee reliable result interpretation of data stemming from small samples. RESULTS: The discrimination ability of each neuropsychological measure varied depending on the pairs of ATN categories compared. The best-discriminating predictor in the Alzheimer's continuum vs. normal biomarkers comparison was the figure naming ability. In contrast, in the Alzheimer's continuum vs. non-AD pathologic change comparison the best predictor was the wordlist forgetting rate. CONCLUSIONS: Although the study was exploratory in nature, the proposed methodological approach may have the potential to identify the best neuropsychological measures for estimating AD neuropathological changes, leading to a more biologically informed use of neuropsychological assessment.

Establishing links between abnormal eating behaviours and semantic deficits in dementia.

The hypothesis that semantic deficits in dementia may contribute in producing changes in eating preferences has never been experimentally investigated despite this association has been clinically observed. We administered tasks assessing semantic memory and the Appetite and Eating Habits Questionnaire (APEHQ) to 23 patients with dementia (behavioural frontotemporal dementia, primary progressive aphasia, and Alzheimer's disease) and to 21 healthy controls. We used voxel-based morphometry and diffusion tensor imaging to identify regions and white matter tracts of significant atrophy associated with the performance at the semantic tasks and the pathological scores at the APEHQ. We observed that the lower the patients' scores at semantic tasks, the higher their changes in eating habits and preferences. Both semantic disorders and eating alterations correlated with atrophy in the temporal lobes and white matter tracts connecting the temporal lobe with frontal regions such as the arcuate fasciculus, the cingulum, and the inferior longitudinal fasciculus. These results confirm that semantic deficits underlie specific eating alterations in dementia patients.

α-Synuclein RT-QuIC assay in cerebrospinal fluid of patients with dementia with Lewy bodies.

We applied RT-QuIC assay to detect α-synuclein aggregates in cerebrospinal fluid (CSF) of patients with suspected Creutzfeldt-Jakob disease who had a neuropathological diagnosis of dementia with Lewy bodies (DLB) (n = 7), other neurodegenerative diseases with α-synuclein mixed pathology (n = 20), or without Lewy-related pathology (n = 49). The test had a sensitivity of 92.9% and specificity of 95.9% in distinguishing α-synucleinopathies from non-α-synucleinopathies. When performed in the CSF of patients with DLB (n = 36), RT-QuIC was positive in 17/20 with probable DLB, 0/6 with possible DLB, and 0/10 with Alzheimer disease. These results indicate that RT-QuIC for α-synuclein is an accurate test for DLB diagnosis.

Connected Speech Deficit as an Early Hallmark of CSF-defined Alzheimer's Disease and Correlation with Cerebral Hypoperfusion Pattern.

BACKGROUND: Diagnosis of prodromal Alzheimer's disease (AD) still represents a hot topic and there is a growing interest for the detection of early and non-invasive biomarkers. Although progressive episodic memory impairment is the typical predominant feature of AD, communicative difficulties can be already present at the early stages of the disease. OBJECTIVE: This study investigated the narrative discourse production deficit as a hallmark of CSFdefined prodromal AD and its correlation with cerebral hypoperfusion pattern. METHODS: Narrative assessment with a multilevel procedure for discourse analysis was conducted on 28 subjects with Mild Cognitive Impairment (15 MCI due to AD; 13 MCI non-AD) and 28 healthy controls. The diagnostic workup included CSF AD biomarkers. Cerebral hypoperfusion pattern was identified by SPECT image processing. RESULTS: The results showed that the discourse analysis of global coherence and lexical informativeness indexes allowed to identify MCI due to AD from MCI non-AD and healthy subjects. These findings allow to hypothesize that the loss of narrative efficacy could be a possible early clinical hallmark of Alzheimer's disease. Furthermore, a significant correlation of global coherence and lexical informativeness reduction with the SPECT hypoperfusion was found in the dorsal aspect of the anterior part of the left inferior frontal gyrus, supporting the hypothesis that this area has a significant role in communicative efficacy, and in particular, in semantic selection executive control. CONCLUSION: This study contributes to the understanding of the neural networks for language processing and their involvement in prodromal Alzheimer's disease. It also suggests an easy and sensitive tool for clinical practice that can help identifying individuals with prodromal Alzheimer's disease.

A new MAPT deletion in a case of speech apraxia leading to corticobasal syndrome.

Speech apraxia is a disorder of speech motor planning/programming leading to slow rate, articulatory distortion, and distorted sound substitutions. We describe the clinical profile evolution of a patient presenting with slowly progressive isolated speech apraxia that eventually led to the diagnosis of corticobasal syndrome (CBS), supporting the evidence that this rare speech disorder can be the first presentation of CBS. Moreover, we found a novel variant in MAPT gene, which is hypothesized to be disease-causing mutation. These results underscore the importance of genetic analysis - particularly in selected atypical cases - for in vivo understanding of possible pathophysiological disease process.

Memorization Test and Resting State EEG Components in Mild and Subjective Cognitive Impairment.

BACKGROUND: Mild (MCI) and Subjective Cognitive Impairment (SCI) are conditions at risk of developing Alzheimer's disease (AD). Differential between normal aging at early stages can be really challenging; available biomarkers need to be combined and can be quite invasive and expensive. OBJECTIVE: The aim of this pilot study is to examine possible EEG alterations in MCI and SCI compared to controls, analyzing if a cognitive task could highlight early AD hallmarks. METHOD: We recruited 11 MCI, 8 SCI and 7 healthy subjects as controls (CS), all matched for age and education. Neuropsychological assessment and EEG recording, at resting state and during a mental memory task, were performed. Classical spectral measures and nonlinear parameters were used to characterize EEGs. RESULTS: During cognitive task, α-band power reduction was found predominantly in frontal regions in SCI and CS, diffused to all regions in MCI; moreover, decreased EEG complexity was found in SCI compared to controls. The α -band power attenuation restricted to frontal regions in SCI during a free recall task (involving frontal areas), suggests that MCI patients compensate for encoding deficit by activating different brain networks to perform the same task. Furthermore, EEG complexity reduction - that has been found already in SCI - could be a possible early hallmark of AD. CONCLUSION: This study draws attention on the importance of nonlinear approach in EEG analysis and the potential role of cognitive task in highlighting EEG alterations at very early stages of cognitive impairment; EEG could therefore have a practical impact on dementia diagnosis.

Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples.

Importance: Early and accurate in vivo diagnosis of Creutzfeldt-Jakob disease (CJD) is necessary for quickly distinguishing treatable from untreatable rapidly progressive dementias and for future therapeutic trials. This early diagnosis is becoming possible using the real-time quaking-induced conversion (RT-QuIC) seeding assay, which detects minute amounts of the disease-specific pathologic prion protein in cerebrospinal fluid (CSF) or olfactory mucosa (OM) samples. Objective: To develop an algorithm for accurate and early diagnosis of CJD by using the RT-QuIC assay on CSF samples, OM samples, or both. Design, Setting, and Participants: In this case-control study, samples of CSF and OM were collected from 86 patients with a clinical diagnosis of probable (n = 51), possible (n = 24), or suspected (n = 11) CJD and 104 negative control samples (54 CSF and 50 OM). The CSF and OM samples were analyzed using conventional RT-QuIC. The CSF samples underwent further testing using improved RT-QuIC conditions. In addition, the diagnostic performance of a novel, easy-to-use, gentle flocked swab for sampling of OM was evaluated. Data were collected from January 1 to June 30, 2015. Main Outcome and Measures: Correlations between RT-QuIC results and the final diagnosis of recruited patients. Results: Among the 86 patients (37 men [43%] and 49 women [57%]; mean [SD] age, 65.7 [11.5] years) included for analysis, all 61 patients with sporadic CJD had positive RT-QuIC findings using OM or CSF samples or both for an overall RT-QuIC diagnostic sensitivity of 100% (95% CI, 93%-100%). All patients with a final diagnosis of non-prion disease (71 CSF and 67 OM samples) had negative RT-QuIC findings for 100% specificity (95% CI, 94%-100%). Of 8 symptomatic patients with various mutations causing CJD or Gerstmann-Sträussler-Scheinker syndrome, 6 had positive and 2 had negative RT-QuIC findings for a sensitivity of 75% (95% CI, 36%-96%). Conclusions and Relevance: A proposed diagnostic algorithm for sporadic CJD combines CSF and OM RT-QuIC testing to provide virtually 100% diagnostic sensitivity and specificity in the clinical phase of the disease.

Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. METHODS: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). RESULTS: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. CONCLUSIONS: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.

The processing of actions and action-words in amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with prime consequences on the motor function and concomitant cognitive changes, most frequently in the domain of executive functions. Moreover, poorer performance with action-verbs versus object-nouns has been reported in ALS patients, raising the hypothesis that the motor dysfunction deteriorates the semantic representation of actions. Using action-verbs and manipulable-object nouns sharing semantic relationship with the same motor representations, the verb-noun difference was assessed in a group of 21 ALS-patients with severely impaired motor behavior, and compared with a normal sample's performance. ALS-group performed better on nouns than verbs, both in production (action and object naming) and comprehension (word-picture matching). This observation implies that the interpretation of the verb-noun difference in ALS cannot be accounted by the relatedness of verbs to motor representations, but has to consider the role of other semantic and/or morpho-phonological dimensions that distinctively define the two grammatical classes. Moreover, this difference in the ALS-group was not greater than the noun-verb difference in the normal sample. The mental representation of actions also involves an executive-control component to organize, in logical/temporal order, the individual motor events (or sub-goals) that form a purposeful action. We assessed this ability with action sequencing tasks, requiring participants to re-construct a purposeful action from the scrambled presentation of its constitutive motor events, shown in the form of photographs or short sentences. In those tasks, ALS-group's performance was significantly poorer than controls'. Thus, the executive dysfunction manifested in the sequencing deficit -but not the selective verb deficit- appears as a consistent feature of the cognitive profile associated with ALS. We suggest that ALS can offer a valuable model to study the relationship between (frontal) motor centers and the executive-control machinery housed in the frontal brain, and the implications of executive dysfunctions in tasks such as action processing.

Neuropsychological, behavioral, and anatomical evolution in right temporal variant frontotemporal dementia: a longitudinal and post-mortem single case analysis.

We describe a patient with semantic variant of frontotemporal dementia who received longitudinal clinical evaluations and structural MRI scans and subsequently came to autopsy. She presented with early behavior changes and semantic loss for foods and people and ultimately developed a pervasive semantic impairment affecting social-emotional as well as linguistic domains. Imaging revealed predominant atrophy of the right temporal lobe, with later involvement of the left, and pathology confirmed bilateral temporal involvement. Findings support the view that left and right anterior temporal lobes serve as semantic hubs that may be affected differentially in semantic variant by early, relatively unilateral damage.

Clinical overlap between Jakob-Creutzfeldt disease and Lewy body disease.

OBJECTIVE: Sporadic Jakob-Creutzfeldt disease (sCJD) and dementia with Lewy bodies (DLB) have overlapping clinical symptoms that can lead to their misdiagnosis. We delineated the clinical overlap between sCJD and DLB, and assessed the value of magnetic resonance imaging (MRI) to differentiate between them. METHODS: Medical records, MRI, electroencephalogram (EEG) and cerebrospinal fluid (CSF) were reviewed from 56 sCJD and 30 DLB subjects. RESULTS: 46% of sCJD subjects met probable DLB criteria and 40% of DLB subjects met probable CJD criteria. A greater proportion of sCJD subjects had cerebellar signs (66% vs. 10%, p<0.001), myoclonus (64% vs. 30%, p=0.002), and visual symptoms (other than hallucinations) (61% vs. 7%, p<0.001), whereas more DLB subjects had hallucinations (70% vs. 39%, p=0.007) and fluctuations (57% vs. 23%, p=0.002). Cortical and/or basal ganglia MRI diffusion weighted imaging hyperintensities consistent with sCJD were seen in 96% of sCJD subjects but in none with DLB. Logistic regression in sCJD revealed that those meeting probable DLB criteria were more likely to have occipital lobe involvement on MRI (OR 1.4, p=0.058, model p=0.022). Parietal lobe involvement on MRI was a predictor of "Other Focal Cortical signs" (OR 1.9, p=0.021). EEG and CSF assessments lacked sensitivity for sCJD as 48% of sCJD patients had a negative EEG; 67% of the 36 sCJD patents with a CSF evaluation had a negative or inconclusive 14-3-3 result. Too few DLB patients had EEG or CSF to assess their utility. CONCLUSION: Sporadic CJD and DLB have significant symptom overlap. MRI helps differentiate these diseases and is related to the signs/symptoms observed in sCJD.

Peripheral neuropathy in hepatitis C virus-related mixed cryoglobulinaemia: existing treatments and a positive symptomatic response to oxcarbazepine.

Peripheral neuropathy is the most common symptom in patients with hepatitis C virus (HCV) associated mixed cryoglobulinaemia, in whom it may be the first clinical manifestation. Very frequently, the medical therapy proposed to treat HCV and cryoglobulinaemia causes an exacerbation of the disabling neuropathy. Therefore, other neuropathy treatments have been proposed, such as alternative immunosuppressive agents (steroids or cyclosporine) and plasma exchange, which, according to case reports, have yielded inconsistent results and presumably exert only temporary effects as they do not promote clearance of HCV. We present five cases of cryoglobulinaemia-related neuropathy resistant to steroids and gabapentin. Oxcarbazepine was introduced and produced moderate and persistent relief of symptoms without side effects.

Cognitive impairment in the lateralized phenotype of corticobasal degeneration.

Corticobasal degeneration (CBD) is a rare disorder, which normally includes a combination of neurobehavioural features, movement disorders and other manifestations. It is now recognized that CBD patients usually present with two phenotypes: the lateralized phenotype and the dementia phenotype. The aim of our work was to determine the nature and the progression of cognitive and behavioural impairment in 10 lateralized CBD patients. In our patients, the most salient aspects of cognitive impairment were: an evident alteration of rapid alternating operative strategies, associated with the evident impairment of set shifting, of executive operations, of operative and sequential procedure and of implementation of judgement and abstract reasoning. The self-activation of retrieval processes is partly preserved in CBD. As all the other types of subcortical impairments, even CBD encompasses both cognitive impairment as well as a wide range of behaviour disturbances, such as progressive alterations of sleep, depression, and of anxiety (with a remarkable incidence of somatic pain). This suggests that in addition to neuropsychological assessment, quantification of the personality behaviour disorder is important for standardizing the diagnosis of subcortical vascular dementia and distinguishing it from any other dementias.

Olanzapine as a possible treatment of behavioral symptoms in vascular dementia: risks of cerebrovascular events. A controlled, open-label study.

Behavioral problems produce excess disability, potentially devastating in cognitively impaired patients. These behavioral symptoms can be a major cause of stress, anxiety and concern for caregivers. While psychotropic drugs are frequently used to control these symptoms, they have the potential for significant side effects, which include sedation, disinhibition, depression, falls, incontinence, parkinsonism and akathisia. We followed up (for 12 months) a group of 346 consecutive outpatients, with a diagnosis of subcortical vascular dementia or multi-infarctual dementia. Patients eligible for this open-label study were required to have behavioral problems (BPSD). Patients were divided into two groups, Group A received olanzapine 2.5-7.5 mg/day while Group B received typical antipsychotics. Patients in both groups were allowed to continue any previous therapy. Patients in both groups were significantly improved in their BPSD. Our patients had a host of medical conditions and received numerous concomitant medications. Given the potential complications associated with these therapeutic agents, these patients tolerated olanzapine quite well. On examination of consequences of adverse events, particularly somnolence, postural instability, and postural hypotension, it appeared that cerebrovascular events were not present. Moreover, no anticholinergic effect was recorded. These findings suggest that olanzapine could be a safe and effective treatment even for elderly population in suitable doses and receiving the adequate follow-up.

Frontal lobe dementia and subcortical vascular dementia: a neuropsychological comparison.

We compared the performance of 40 patients with frontal lobe dementia to that of 40 patients with subcortical vascular dementia (80 patients including, 46 men and 34 women) in a set of tasks assessing attentional, executive, and behavioural tasks. The frontal lobe dementia represents an important cause for degenerative disruption and is increasingly recognised as an important form (up to 25%) of degenerative dementia among individuals of late-middle-age. The main involvement is the frontal-subcortical pathway, which is the final target of impairment even in subcortical vascular dementia. A wider involvement of the cortical (decisional) layers in frontal dementia, in contrast with the prominent and widespread involvement of the subcortical pathways (refinement and corrections programs) creates the different profiles of the two groups. Frontal patients have more difficulties in abstract reasoning, focusing attention, and implementing strategies to solve problems. They exhibit more profound behavioural alterations in personality and social conduct and show only moderate depression, and a total lack of insight concerning their dinical condition. In contrast, the patients with subcortical vascular dementia have poor general cognitive functions, high insight, and important depression and apathy as the principal and most salient characteristic of their behavioral conduct.

Neuropsychological evaluation of late-onset post-radiotherapy encephalopathy: a comparison with vascular dementia.

It is known that radiotherapy (RT) may cause cerebral injury. The most frequent neurotoxic effect of RT at any age is diffuse cerebral injury. Brain injury by therapeutic irradiation has traditionally been classified according to its time of onset into acute, early delayed, and late forms. The latter is not reversible. The neurocognitive sequelae of cranial irradiation can be mediated through vascular injury. Because the pathologic changes are most profound in the white matter, we compared a group of patients treated by RT (n=34) with a group of patients affected by subcortical vascular dementia (sVaD, n=34). Patients with a total radiation does <35 cGy did not show any sign of cognitive impairment. All the patients with a total irradiation dose >45 cGy did show profound cognitive and behavioural alteration. The patients who received a total dose of brain radiation comprised between 35 and 45 cGy did show slowness of executive function, and profound alterations of frontal functions, such as attention focusing, mentation control, analogical judgement and insight. The patients who suffered from the consequences of RT had slowness of executive functions, and profound alterations of frontal functions, such as attention focusing, mentation control, analogical judgement and insight, similar to those obtained by the patients suffering from subcortical vascular dementia. High dose RT might result in a severely demented, bedridden patient, who "has been cured" from his primary disease, the brain tumour. This constellation demands serious consideration before RT is given.

Rivastigmine in frontotemporal dementia: an open-label study.

OBJECTIVE: This preliminary open-label study aims to investigate the effects of rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), in 20 patients diagnosed with frontotemporal dementia (FTD). PATIENTS AND METHODS: Study subjects were men and women 60-75 years of age diagnosed with probable FTD. The rivastigmine group received doses of 3-9 mg/day. The control group included matched patients receiving antipsychotics, benzodiazepines and selegiline (deprenyl). All patients completed a 12-month follow-up period. RESULTS: Rivastigmine treatment was well tolerated. At 12 months, there was a general amelioration of behavioural changes as demonstrated by reductions in Neuropsychiatric Inventory (p<0.001 vs baseline and control), Behavioral Pathology in Alzheimer's Disease Rating Scale (p<0.001 vs baseline and control) and Cornell Scale for Depression in Dementia scores (p<0.05 vs baseline, p<0.001 vs control) in the rivastigmine group. Caregiver burden was reduced, as shown by reduced Relative Stress Scale scores (p<0.001 vs baseline and control). Mean scores on outcome measures evaluating executive function stabilised in the rivastigmine group (p<0.05 vs controls). Rivastigmine did not prevent the disease-related deterioration of cognition as assessed using the Mini-Mental State Examination. CONCLUSION: In this open-label study, rivastigmine-treated patients were less behaviourally impaired, and caregiver burden was reduced, at 12 months, compared with baseline. The use of cholinesterase inhibitors in FTD warrants further research.

Vitamin B12 and folate depletion: clinical evidence in a neurological population.

In cross-sectional studies, low levels of folate and vitamin B12 have been associated with poor cognition and dementia. Results are quite controversial and a debate continues in the literature. Still not completely understood are the differential roles of folate and vitamin B12 in memory acquisition and cognitive development. More intriguing and not fully understood is the rule that treating a vitamin B12-deficient patient with folate may exacerbate the neurological consequences of either deficiency. Starting from these quite confusing perspectives, the aim of this study was to define a possible role of vitamin B12 and folate in cognitive disruption. Data were collected among a cohort of people, admitted to the Neurology Clinic of the University of Trieste, in a period between November 1,2000, and November 1, 2002. We examine potential risk factors, concomitant drug-therapies, and cognitive global performance and correlate these parameters with folate and vitamin B 12 serum levels.We discuss the results with an overview of the literature.