Salvatore Caratozzolo

Transcranial magnetic stimulation distinguishes Alzheimer disease from frontotemporal dementia

Objective: To determine whether a transcranial magnetic stimulation (TMS) multiparadigm approach can be used to distinguish Alzheimer disease (AD) from frontotemporal dementia (FTD). Methods: Paired-pulse TMS was used to investigate short-interval intracortical inhibition (SICI) and facilitation (ICF), long-interval intracortical inhibition, and short-latency afferent inhibition (SAI) to measure the activity of different intracortical circuits in patients with AD, patients with FTD, and healthy controls (HC). The primary outcome measures were sensitivity and specificity of TMS measures, derived from receiver operating curve analysis. Results: A total of 175 participants met the inclusion criteria. We diagnosed 79 patients with AD, 64 patients with FTD, and 32 HC. We found that while patients with AD are characterized by a specific impairment of SAI, FTD shows a remarkable dysfunction of SICI-ICF intracortical circuits. With the use of the best indexes, TMS differentiated FTD from AD with a sensitivity of 91.8% and specificity of 88.6%, AD from HC with a sensitivity of 84.8% and specificity of 90.6%, and FTD from HC with a sensitivity of 90.2% and specificity of 78.1%. These results were confirmed in patients with mild disease. Conclusions: TMS is a noninvasive procedure that reliably distinguishes AD from FTD and HC and, if these findings are replicated in larger studies, could represent a useful additional diagnostic tool for clinical practice. Classification of evidence: This study provides Class III evidence that TMS measures can distinguish patients with AD from those with FTD.

Knowledge and attitudes about Alzheimer’s disease in the lay public: influence of caregiving experience and other socio-demographic factors in an Italian sample

Background and aims: Despite increasing attention on the knowledge of dementia among patients and family members, little is known about the general public’s level of understanding about dementia. The aim of this study was to assess the influence of the caregiving experience, sex and age on the knowledge of AD. Methods: Eleven hundred and eleven individuals were enrolled. They fulfilled a questionnaire made of 25 questions. The questionnaires were submitted in the waiting rooms of several departments of the Hospital “Spedali Civili di Brescia”. The questionnaires assessed several issues, including the general knowledge about Alzheimer’s disease, the management and ethical problems. The present study is focused on the analysis of 9 of the 25 questions included in the questionnaire, highlighting aspects about knowledge of symptoms, risk factors, therapies and services. Results: The percentage of correct responses was significantly greater among the caregivers. The group of old respondents gave similar answers, independently of their caregiving status. Women, caregivers or not, are the more knowledgeable group. Conclusion: The entire population needs accurate information, but education programs should be specifically tailored for the different sections of the population because they may start with different levels of knowledge.

The impact of cognitive deficit on self-reported car crashes in ultra-octogenarian population: data of an Italian population-based study

To examine the usefulness of specific neurocognitive tests for predicting the crash involvement in ultra‐octogenarian population.

Discrimination of atypical parkinsonisms with transcranial magnetic stimulation

BACKGROUND Differential diagnosis of atypical parkinsonian disorders, i.e. dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS) still remains problematic. Furthermore, DLB may overlap with Alzheimers disease (AD) in the early stages of disease. OBJECTIVE To determine whether transcranial magnetic stimulation (TMS) can be used to classify atypical parkinsonian disorders and AD. METHODS A paired-pulse TMS multi-paradigm approach assessing multiple intracortical circuits, as short interval intracortical inhibition-facilitation and short latency afferent inhibition, was used to model a decision tree analysis and determine diagnostic accuracy in classifying different neurodegenerative disorders. RESULTS We observed a significant impairment in short latency afferent inhibition in AD and DLB and a significant impairment in short interval intracortical inhibition-facilitation in DLB, PSP and CBS patients. These parameters were used to model a decision tree analysis which yielded an overall diagnostic accuracy of 88.3%, with 90.5% for AD, 85.2% for DLB, 76.0% for CBS-PSP, and 94.9% for healthy controls. CONCLUSIONS The assessment of intracortical connectivity with TMS may aid in the differential diagnosis of AD and the atypical parkinsonian disorders.

Dementia after Three Months and One Year from Stroke: New Onset or Previous Cognitive Impairment?

OBJECTIVE Stroke is an important risk factor for dementia, but the exact mechanism involved in cognitive decline remains unclear. METHODS Patients were divided into 2 groups: poststroke dementia group (PSD) and poststroke nondementia group (PSND). Variables and neuroradiological hallmarks were compared between 2 groups at 3 months (114 subjects) and 1 year (105 subjects) after stroke. RESULTS Older age (OR 1.11, 95% CI 1.0-1.2; P < .05), education (OR .6, 95% CI .4-.8; P < .05), prestroke IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly; OR .78, 95% CI .1-5.9; P < .05), premorbid apathy (OR 2.03, 95% CI 1.1-3.7; P < .05), and medial temporal lobe atrophy (MTLA) (OR 6.14, 95% CI 1.4-26.2; P < .05) were independently associated with PSD at 3 months after a cerebrovascular event, whereas at 1-year follow-up older age (OR 1.1, 95% CI 1.0-1.2; P < .05), prestroke IQCODE (OR .05, 95% CI .0-.9; P < .05), MTLA (OR 1.3, 95% CI 1.0-1.6; P < .05), and APACHE II (Acute Physiology and Chronic Health Evaluation; OR .6, 95% CI .4-.9; P < .05) were independently associated with PSD. CONCLUSIONS Acute cerebrovascular disease could not be the only one mechanism explaining PSD. Neurodegenerative pathology must be taken into account.

Prestroke Dementia: Characteristics and Clinical Features in Consecutive Series of Patients

Background/Aim: The prestroke level of cognitive function should be taken into account in order to predict the impact of stroke on the subsequent risk of dementia. The aim of the present study was to investigate the presence and correlates of prestroke dementia (PSD) as well as to identify its clinical features. Methods: Premorbid clinical and cognitive features of 158 consecutively recruited patients with a diagnosis of acute cerebrovascular pathology were assessed by interviewing the caregivers using multidimensional assessment. Patients were divided into two groups (PSD group and prestroke nondemented group). Baseline cognitive, functional and behavioral variables and neuroradiological hallmarks (medial temporal lobe atrophy, MTLA) were compared between these two groups. Results: In a logistic regression model, older age (OR 1.05), female gender (OR 2.3), Neuropsychiatric Inventory total score (OR 1.1) and MTLA (OR 1.2) were the variables independently associated with PSD. Conclusions: These findings support the hypothesis that cognitive impairment in patients with stroke may not only be a direct consequence of the acute cerebrovascular event but also a consequence of underlying neurodegenerative pathology.

Potentially Serious Drug-Drug Interactions in Older Patients Hospitalized for Acute Ischemic and Hemorrhagic Stroke.

Background: Polypharmacy is very common in older persons and it is associated with inappropriate prescribing and potential drug-drug interactions (DDIs). Aims of this study were to identify prevalence of DDIs in older persons with acute stroke and to evaluate the association between stroke and DDIs. Methods: One hundred forty-six patients admitted with diagnosis of acute stroke were enrolled. The therapeutic regimen of patients was analyzed at admission to identify the number of DDIs, prevalence and sorts of serious DDIs according to subtype of acute stroke (ischemic or hemorrhagic) and to its recurrence. Results: Five hundred eighty-two DDIs were identified: 18 mild, 415 moderate and 149 serious. Sixty-one percent of patients were exposed to at least one serious DDI. A higher percentage of patients were exposed to at least one serious DDI among those with a recurring ischemic event compared to those with a first event (74 vs. 50%; p < 0.01, respectively). Serious DDIs potentially associated with an increased risk of a cerebral event were identified in 19 (17%) patients with ischemic stroke, and in 7 (19%) patients with hemorrhagic stroke. Conclusions: The prevalence of serious DDIs was high in aging patients with acute stroke but different according to subtype and recurrence of the cerebrovascular event.

Diagnosis of Mild Cognitive Impairment Due to Alzheimer’s Disease with Transcranial Magnetic Stimulation

BACKGROUND Considering the increasing evidence that disease-modifying treatments for Alzheimers disease (AD) must be administered early in the disease course, the development of diagnostic tools capable of accurately identifying AD at early disease stages has become a crucial target. In this view, transcranial magnetic stimulation (TMS) has become an effective tool to discriminate between different forms of neurodegenerative dementia. OBJECTIVE To determine whether a TMS multi-paradigm approach can be used to correctly identify mild cognitive impairment (MCI) due to AD (AD MCI). METHODS A sample of 69 subjects with MCI were included and classified as AD MCI or MCI unlikely due to AD (non-AD MCI) based on 1) extensive neurological and neuropsychological evaluation, 2) MRI imaging, and 3) cerebrospinal fluid analysis or/and amyloid PET imaging. A paired-pulse TMS multi-paradigm approach assessing short interval intracortical inhibition-facilitation (SICI-ICF), dependent on GABAergic and glutamatergic intracortical circuits, respectively, and short latency afferent inhibition (SAI), dependent on cholinergic circuits, was performed. RESULTS We observed a significant impairment of SAI and unimpaired SICI and ICF in AD MCI as compared to non-AD MCI. According to ROC curve analysis, the SICI-ICF / SAI index differentiated AD MCI from non-AD MCI with a specificity of 87.9% and a sensitivity of 94.4%. CONCLUSIONS The assessment of intracortical connectivity with TMS could aid in the characterization of MCI subtypes, correctly identifying AD pathophysiology. TMS can be proposed as an adjunctive, non-invasive, inexpensive, and time-saving screening tool in MCI differential diagnosis.

Does Age at Observation Time Affect the Clinical Presentation of Mild Cognitive Impairment

Background: To date, there are no published data investigating the role of age in the clinical and neuropsychological presentation of mild cognitive impairment (MCI). The aim of the study was to evaluate whether age at the time of evaluation modulates clinical, functional or cognitive profiles in MCI subjects. Methods: A total of 167 outpatients with a clinical diagnosis of MCI were consecutively enrolled and entered in the study. Clinical and demographic characteristics were carefully recorded. Each patient underwent a wide neuropsychological standardized assessment. Results: MCI subjects were divided into 3 groups according to their age at observation time: 58 MCI patients were classified as young (≤69 years), 89 as old (70–79 years) and 20 as very old (≧80 years). The 3 groups did not differ in demographic characteristics, general cognitive functions and memory impairment. Very old MCI subjects showed a significantly greater impairment than younger MCI patients in cognitive domains involving executive functions. In particular, very old MCI patients were more frequently classified as having multiple-domain amnestic MCI. Conclusion: Present data highlight that the clinical presentation of MCI is affected by age: at presentation, very old MCI subjects show a worse performance than younger MCI subjects on multiple abilities, particularly on executive functions.

OnabotulinumtoxinA in chronic migraine: long-term efficacy in a prophylactic medication free cohort

Chronic migraine (CM) is a debilitating neurologic disorder defined as headaches occurring on ≥ 15 days per month for more than 3 months, with headaches having migraine features on ≥ 8 days per month. Patients with chronic migraine typically have a history of episodic migraine headaches that increase in frequency over a period of months to years until patients experience daily or near-daily, low-grade migraineous and nonmigraineous headaches with intermittent attacks of severe migraine. CM affects approximately 1.4 to 2.2% of adults worldwide with an important economic burden and impact in quality of life. Both frequency of attacks, severity of pain, and associated symptoms have a major role on migraine-related disability. The current understanding of headache pathophysiology is evolving. For patients affected by CM, a prophylactic headache treatment regimen is highly recommended to reduce the frequency, severity, and disability. OnabotulinumtoxinA is a focally acting protein that inhibits the release of the neurotransmitter acetylcholine from the presynaptic nerve endings and blocks the neuronal release of nociceptive mediators such as substance P, glutamate, and calcitonin gene-related peptide (CGRP) in the periphery, which suggests it may possess peripheral antinociceptive activity. The inhibition of nociceptive mediators in the periphery may reduce central sensitization, perhaps by inhibiting afferent inputs to the central nervous system, thereby reducing inflammatory signals to sensitized regions in the brain. Its biological effects are transient, and within approximately 3 months, normal neuronal signaling is restored. The recently published PREEMPT [1] and COMPEL [2] studies established the safety and efficacy of OnabotulinumtoxinA for treatment of chronic migraine. The a im of the presen t s tudy was to assess OnabotulinumtoxinA long-term efficacy in CM patients as a prophylactic agent alone.Moreover, subjects who presented with a diagnosis of chronic migraine with medication overuse headache were treated directly with OnabotulinumtoxinA, sidestepping withdrawal interventions, althought such bridge therapies are generally regarded as crucial for subsequent prophylaxis’ efficacy. The study was conducted at the Headache Centre of Neurological Department of ASST Spedali Civili of Brescia. We evaluated prospectively all patients aged 18 to 65 years with CMwith orwithout a diagnosis ofmedical overuse headache between 1 January 2015 and 31 December 2017. Diagnosis was made according to the ICHD III beta criteria [3]. During the study, preventive treatments were not allowed. We collected data concerning demographic variables: pain site, disease duration, previous prophylaxis therapies, monthly number of days with headache (distinguished according with intensity of pain), and symptomatic drug consumption (triptans, NSAIDs and combination analgesics). We collected the same variables at each subsequent evaluation every 3 months by analysis of headache diary provided at our center. Migraine-induced disability was assessed using the Migraine Disability Assessment Score Questionnaire (MIDAS) at baseline and 3, 6, and 9 months after treatment. Patients were injected OnabotulinumtoxinA according to the PREEMPT protocol. We administered 155 units intramuscularly in 31 sites. At the investigator’s discretion, an additional 20 units could be administered using a follow-the-pain strategy based on the patient’s report of predominant pain location. The primary endpoint was to evaluate the reduction in the headache frequency at 3, 6, and 9 months after the discontinuance of the treatment. Secondary endpoints were evaluation of reduction in intensity of pain, symptomatic medication intake, * Francesca Schiano di Cola francescaschiano@hotmail.it