Tatiana Cattaruzza

Rivastigmine in frontotemporal dementia: an open-label study.

ObjectiveThis 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 MethodsStudy 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.ResultsRivastigmine 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.ConclusionIn 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.

Cholinesterase inhibition as a possible therapy for delirium in vascular dementia: A controlled, open 24-month study of 246 patients:

The goal of this study was to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effect on delirium in vascular dementia (VaD). The results from this follow-up study suggest that although delirium is frequent in elderly, cognitively impaired patients, it might not be a simple consequence of acute disease and hospitalization. Rather, delirium can be secondary to brain damage and to metabolic disturbances. According to the Lewy body dementia model, delirium could be induced by a lack of acetylcholine in the brain. Rivastigmine may help reduce the frequency of delirium episodes and help shorten their duration. Additional studies are required to better define the causes of delirium, which currently has no definitive treatment.

Olanzapine as a possible treatment of behavioral symptoms in vascular dementia: risks of cerebrovascular events

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.

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.

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 clinical 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.

Olanzapine as a possible treatment for anxiety due to vascular dementia: An open study:

Disabilities caused by behavioral problems can be 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 can be accompanied by significant side effects, which include sedation, disinhibition, depression, falls, incontinence, parkinsonism, and akathisias. Agitation is a major problem in older patients with dementia. Agitation and aggression have always been difficult behaviors to manage, and when it is severe, agitation can be a behavioral emergency that requires urgent and immediate intervention. This six-month study included a group of 94 outpatients (48 men and 46 women) who had a diagnosis of subcortical vascular dementia (VaD). To be eligible for the study, patients needed a score of at least 3 for agitation/ aggression on the Neuropsychiatric Inventory (NPI), suggesting at least moderate frequency and/or severity, and 0 for delusions and hallucinations. Patients were divided into two homogenous groups. Group A received olanzapine (2.5-5 mg/day) and Group B received bromazepam (0.25 percent, 15 drops, three times per day). Patients in both groups were allowed to continue any previous therapy. Patients receiving olanzapine at an average dose of 3.21 ± 1.02 mg/day showed statistically significant improvement on the anxiety rating compared with those receiving bromazepam. 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. It appeared that adverse events, particularly somnolence, postural instability, and postural hypotension, were mild and transient. Moreover, no anticholinerigic effect was registered. These findings suggest that olanzapine could be a safe and effective treatment for anxiety in cognitively impaired patients.

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 B12 serum levels. We discuss the results with an overview of the literature.

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.

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

ABSTRACT 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 Alzheimers 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.