Rodolfo M. Antonello

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.

Frontotemporal Dementia: Paroxetine as a Possible Treatment of Behavior Symptoms

Frontotemporal dementia (FTD) represents an important cause for degenerative disruption and is increasingly recognized as an important cause (up to 25%) of degenerative dementia among late-middle-age individuals. The serotoninergic system is tightly bound to frontal circuits, whose degeneration subserves FTD. Patients aged 64–68 years, with a diagnosis of FTD, were randomized to receive paroxetine up to 20 mg/day (n = 8) or piracetam up to 1,200 mg/day (n = 8). At 14 months, the patients treated with paroxetine showed significant improvements in behavioral symptoms, reflected by a reduction of caregiver stress. Side effects were easily tolerable, and there was no dropout. The results are presented with an overview of the literature on the topic.

Rivastigmine in subcortical vascular dementia: an open 22-month study.

Further to recent data indicating that patients with vascular dementia (VaD) show a cholinergic deficit, we aimed to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effects on the symptoms of VaD. Patients aged 65-80, with a diagnosis of dementia and probable VaD, received rivastigmine 3-6 mg/day (n=8) or cardioaspirin (n=8) in an open study for 22 months. At 22 months, patients treated with rivastigmine showed significant improvements in executive function and behavioural symptoms (both p<0.05 vs. both baseline and control group), which were reflected in reduced caregiver stress (p<0.05 vs. baseline and controls). Baseline scores of global response, cognition, word fluency and activities of daily living were maintained in patients receiving rivastigmine, and there was no increase in benzodiazepine or neuroleptic intake. In contrast, the control group showed no improvements in any domain, and significant deterioration in global response and executive function (both p<0.05 vs. baseline and rivastigmine group). Side effects in both groups were tolerable and there were no study withdrawals. Long-term rivastigmine treatment appeared to be safe and effective in this patient population. In particular, improvements in domains particularly relevant to this condition were observed. These benefits may reflect the drugs dual inhibitory effects on the cholinergic system, and its particular activity in frontal areas of the brain. A large, double-blind study of rivastigmine in patients with VaD would be worthwhile.

Olanzapine as a treatment of neuropsychiatric disorders of Alzheimer's disease and other dementias: a 24-month follow-up of 68 patients.

Although the core feature of all types of dementia is progressive cognitive disruption, most demented patients also express noncognitive behavioral problems. These noncognitive problems lead to potentially devastating disabilities, and are often a major cause of stress, anxiety and concern for caregivers. Psychotropic drugs are frequently used to control these symptoms, but they have the potential for significant side effects, such as sedation, disinhibition, depression, falls, incontinence, parkinsonisms and akathisias. For 24 months, we monitored 68 outpatients suffering from Alzheimers disease, vascular dementia, frontal lobe dementia, Parkinson dementia complex, and Lewy body disease. Our purpose was to identify the role and efficacy of olanzapine and the side effects which emerged during the treatment of behavioral alteration resulting from five etiological causes. This paper will discuss the results of this study, and will provide an overview of the existing literature.

Risk factors for vascular dementia: Hypotension as a key point

Physiologically, the cerebral autoregulation system allows maintenance of constant cerebral blood flow over a wide range of blood pressure. In old people, there is a progressive reshape of cerebral autoregulation from a sigmoid curve to a straight line. This implies that any abrupt change in blood pressure will result in a rapid and significant change in cerebral blood flow. Hypertension has often been observed to be a risk factor for vascular dementia (VaD) and sometimes for Alzheimer disease although not always. Indeed, high blood pressure may accelerate cerebral white matter lesions, but white matter lesions have been found to be facilitated by excessive fall in blood pressure, including orthostatic dysregulation and postprandial hypotension. Many recent studies observed among other data, that there was a correlation between systolic pressure reduction and cognitive decline in women, which was not accounted for by other factors. Baseline blood pressure level was not significantly related to cognitive decline with initial good cognition. Some researchers speculate that blood pressure reduction might be an early change of the dementing process. The most confounding factor is that low pressure by itself might be a predictor of death; nevertheless, the effect of low blood pressure on cognition is underestimated because of a survival bias. Another explanation is that clinically unrecognized vascular lesions in the brain or atherosclerosis are responsible for both cognitive decline and blood pressure reduction. We discuss the entire process, and try to define a possible mechanism that is able to explain the dynamic by which hypotension might be related to dementia.

Reading errors in patients with cerebellar vermis lesions

Abstract Dyslexia, both developmental and acquired, has been considered the result of cerebrocortical dysfunction, affecting the temporo-parieto-occipital brain regions. However, dyslexia may involve abnormalities of the magnocellular component of the visual system, leading to binocular instability or alterations of accommodation. To test the hypothesis of cerebellar involvement in the reading process – justified by its emergent role in language and cognition – we studied 10 patients with cerebellar vermis/paravermis lesions using reading tests and we compared the results with those produced by 10 normal volunteers. The data obtained demonstrate an increased number of reading mistakes in the patient group, resulting from a possible alteration of the diffuse connection system from the cerebellum to different cerebrocortical and subcortical structures. Acquired dyslexia due to cerebellar impairment may be due to oculomotor alteration or, more subtly, to the intimate cerebellar-encephalic projections, connecting the cerebellum to the attentive and alerting processes and to the language system. We discuss the data with an overview of literature.

Depression and Alzheimer's disease: Symptom or comorbidity?

Alzheimers disease is the most frequent form of dementia, where behavioral and cognitive disruption symptoms coexist. Depression, apathy, anxiety, and other conduct disorders are the complaints most often reported by caregivers. Fifty subjects were referred to our Institute with a diagnosis of probable Alzheimers disease. Cognitive impairment was equally distributed among the subjects. Patients, aged 68 to 76 years old, were randomized to receive inhibitors of cholinesterase (Donepezil, 5 mg/ day) alone, or inhibitors of cholinesterase plus selective seratonin reuptake inhibitors (SSRIs) (citalopram HBr, 20 mg/day). We followed up all the patients for one year, with particular concern for neuropsychological aspects associated with eventual behavioral changes. Results indicate that SSRI intake seems to be effective for depression, decreasing it and improving quality of life for both patients and caregivers. Side effects in both groups were few, and there were no study withdrawals. This paper discusses the relationship between dementia-and depression, and presents our finding that depressive symptoms, if specifically treated, tend to reduce caregiver stress and improve well-being in patients with Alzheimers disease.

Rivastigmine in subcortical vascular dementia: A randomized, controlled, open 12-month study in 208 patients:

Subcortical vascular dementia (VaD) is characterized by executive dysfunction and behavioral problems, reflecting deterioration of the frontal lobe. This study aimed to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effects on the typical symptoms of subcortical VaD. Patients receiving rivastigmine showed a slight improvement in executive functions and in behavior. Side effects in both groups were tolerable and there were no study withdrawals. Moreover, there are no drug interactions with other therapies previously and concomitantly assumed. Improvements in domains that characterize subcortical VaD were observed, indicating that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population.

Olfactory dysfunction and extent of white matter abnormalities in multiple sclerosis: a clinical and MR study

Background: The relative contribution to the olfactory dysfunction of the lesions in the specific brain regions involved in olfaction compared with the lesions scattered all over the rest of the brain has not been fully clarified yet in patients with multiple sclerosis (MS). The concurrent use of Magnetic Resonance Imaging (MRI) and a standardized test of odor identification ability now permits to study the relation between smell loss and the extent of white matter abnormalities. Methods: We tested the olfactory function of 40 patients with definite MS and of 40 age-sex- and smoking-habit-matched healthy controls by using the Cross Cultural Smell Identification Test. We measured also the lesion load on T2-weighted images in the inferior-frontal and temporal lobes and in the rest of the brain in MS patients. Therefore, we tried to correlate measures of lesion load and smell test scores. Results: A robust correlation was demonstrated between MR measures of lesion load in the white matter of the olfactory brain region and smell loss (r=70.739, P50.0001). A significant relationship has been found even after taking potential confounding factors, such as sex, age, disease duration, disability, anxiety and depression, into account (r=70.90, P50.0001). Conclusions: Our findings show, in MS patients with stable neurological impairment and no recent disease exacerbation, a correlation between smell loss and the lesion load in the regions of the brain involved in olfaction and support the theory that the extent and severity of MRI abnormalities in specific brain regions are related to the presence of selective neurologic and neuropsychologic impairment.

Persistent aura without infarction: decription of the first case studied with both brain SPECT and perfusion MRI

To the best of our knowledge, persistent visual symptoms, lasting months or years without evidence of infarction, a rare complication of migraine with aura, has been reported in only 20 patients. We report the case of a 43-year-old woman with a 31-year history of migraine with typical visual aura. At presentation, she experienced a visual aura in her right hemifield followed by a pulsating headache. The visual symptoms persisted. There were no abnormal findings on neurological and ophthalmological examinations, EEG, visual evoked potentials (VEPs), brain computed tomography and magnetic resonance imaging (MRI). Both brain single photon emission compted tomography (SPECT) and brain perfusion MRI revealed decreased left fronto-parieto-occipital and right occipital blood perfusion. A perfusion MRI, performed 7 months after symptom onset and almost complete extinction of symptoms, was normal. As previously reported, we demonstrated a cortical hypoperfusion by SPECT in a case of persistent visual aura. For the first time this finding was confirmed by perfusion MRI.