Alessandro Trebbastoni

Choroidal Thinning as a New Finding in Alzheimer's Disease: Evidence from Enhanced Depth Imaging Spectral Domain Optical Coherence Tomography

BACKGROUND The involvement of retina and its vasculature has been recently described in Alzheimers disease (AD). However, none of the previous works have yet investigated the choroid in vivo. OBJECTIVE Spectral domain optical coherence tomography (SD-OCT) and enhanced depth imaging (EDI) technique is non-invasively used to assess choroidal thickness in patients with AD and to determine whether the peripapillary retinal nerve fiber layer (RNFL) and central retinal thickness are reduced compared to normal subjects. METHODS Forty-two eyes of 21 patients (mean age, 73.1 ± 6.9 years) with a diagnosis of mild to moderate AD and 42 eyes of 21 age-matched control subjects (mean age, 70.3 ± 7.3 years) were included in this prospective, cross-sectional study. All the subjects underwent neuropsychological (MMSE, ADAS-Cog, and CDR) and ophthalmological evaluation. The SD-OCT images of the choroid were obtained by EDI modality. Choroidal thickness was assessed by manual measurement. The following parameters, measured automatically by the OCT software, were also analyzed for each eye: 1-mm central subfield (CSF) retinal thickness, peripapillary RNFL thickness. RESULTS Choroidal thickness was significantly thinner in AD than in control eyes (p < 0.05). No difference in CSF retinal thickness was found between groups (p > 0.05). Mean peripapillary RNFL thickness in all four quadrants was similar between groups (p > 0.05). OCT measurements were not correlated with any of the tested psychometric parameters (p > 0.05). CONCLUSION Compared with healthy subjects, patients with AD showed a significant reduction in choroidal thickness. Choroidal thinning may represent an adjunctive biomarker for the diagnosis and follow-up of this disease.

Seizures in Alzheimer’s disease: a retrospective study of a cohort of outpatients

PurposeThe aim of our study was to define the frequency of seizures in a population of outpatients attending a cognitive function clinic in Italy and to identify risk factors for seizures in patients with Alzheimer’s disease.MethodsIn this retrospective study, we analyzed our clinical records to gather information on patients’ demographic, metabolic, cardiovascular and cognitive features. We sought to determine the significance of abnormal neuroimaging findings and the use of potentially epileptogenic drugs on the onset of seizures. From the records of 583 patients referred to the clinic for cognitive disturbances, we identified 145 patients with Alzheimer’s disease.ResultsOf these 145 patients, 14 (9.7%) had a history of complex partial or generalised seizures, or both. Of the risk factors identified, onset of seizures was associated with male gender and none of the patients with seizures had diabetes. The risk of seizure onset was higher in Alzheimer’s disease patients with hyperlipaemia and severe dementia. No other risk factors were identified, although hypertensive patients seemed to be protected.ConclusionsSeizures in Alzheimer’s disease are frequent and often under-recognized. In elderly patients, especially those with Alzheimer’s disease, correct diagnosis and treatment are important to prevent disease from worsening and disability from increasing. Patients with dementia should routinely undergo history-taking designed to elicit a history of seizures and define patients at high risk.

Promoting the Assessment of Frailty in the Clinical Approach to Cognitive Disorders

The need of adapting healthcare systems (originally designed for younger patients with a lower burden of chronic conditions) to the specific needs of older individuals has been repeatedly evoked in light of the rapid aging of our populations (Beard et al., 2016; Cesari et al., 2016a). In this scenario, the so-called “frailty” condition has been attracting special interest. The concept of frailty is today no longer confined within the original geriatric boundaries, being currently implemented in various medical areas, from cardiology (Afilalo et al., 2009) to anesthesiology (Hubbard and Story, 2014), from infectious disease medicine (Brothers et al., 2014) to oncology (Balducci, 2013). It is indeed growingly considered as a crucial aspect for reshaping our healthcare systems, as requested by public health agencies (European Commission, 2015).

Altered Cortical Synaptic Plasticity in Response to 5-Hz Repetitive Transcranial Magnetic Stimulation as a New Electrophysiological Finding in Amnestic Mild Cognitive Impairment Converting to Alzheimer’s Disease: Results from a 4-year Prospective Cohort Study

Introduction To investigate cortical excitability and synaptic plasticity in amnestic mild cognitive impairment (aMCI) using 5 Hz repetitive transcranial magnetic stimulation (5 Hz-rTMS) and to assess whether specific TMS parameters predict conversion time to Alzheimer’s disease (AD). Materials and methods Forty aMCI patients (single- and multi-domain) and 20 healthy controls underwent, at baseline, a neuropsychological examination and 5 Hz-rTMS delivered in trains of 10 stimuli and 120% of resting motor threshold (rMT) intensity over the dominant motor area. The rMT and the ratio between amplitude of the 1st and the 10th motor-evoked potential elicited by the train (X/I-MEP ratio) were calculated as measures of cortical excitability and synaptic plasticity, respectively. Patients were followed up annually over a period of 48 months. Analysis of variance for repeated measures was used to compare TMS parameters in patients with those in controls. Spearman’s correlation was performed by considering demographic variables, aMCI subtype, neuropsychological test scores, TMS parameters, and conversion time. Results Thirty-five aMCI subjects completed the study; 60% of these converted to AD. The baseline rMT and X/I-MEP ratio were significantly lower in patients than in controls (p = 0.04 and p = 0.01). Spearman’s analysis showed that conversion time correlated with the rMT (0.40) and X/I-MEP ratio (0.51). Discussion aMCI patients displayed cortical hyperexcitability and altered synaptic plasticity to 5 Hz-rTMS when compared with healthy subjects. The extent of these changes correlated with conversion time. These alterations, which have previously been observed in AD, are thus present in the early stages of disease and may be considered as potential neurophysiological markers of conversion from aMCI to AD.

Attentional processing in bulbar- and spinal-onset amyotrophic lateral sclerosis: Insights from event-related potentials

Abstract Our objective was to evaluate attentional processing with respect to the clinical-onset subtype in amyotrophic lateral sclerosis (ALS) using event-related potentials (ERPs). Thirty-three non-demented ALS patients (22 spinal onset, 11 bulbar onset) and 32 age- and gender-matched controls underwent a psychophysiological evaluation. Mismatch Negativity (MMN), P300 components and Contingent Negative Variation (CNV) were obtained. Latencies and amplitudes of the MMN, P3a and P3b waves and CNV amplitude were then evaluated. Clinical parameters were correlated with ERP data. No differences emerged between ALS patients and controls with regard to the MMN and P3b components. N1-P3a inter-peak latency (Fz, p = 0.003; Cz, p = 0.001; Pz, p = 0.002) was longer in ALS-b than in ALS-s. Total CNV area (Cz, p = 0.01) and W1-CNV area were significantly reduced (Cz, p = 0.05; Pz, p = 0.03) in ALS-b with respect to the one of the controls, while no differences were found between ALS-s patients and controls. In conclusion, automatic pre-attentive processing of stimuli seems to be preserved in ALS. However, a significant delay in the time-course of selective attentive processing and a difficulty in initiating and sustaining attention may be present in ALS-b, which points to a possible dysfunction in the frontal neural network that responds to novelty and to abnormal integration of associative functions. This attentional impairment should be taken in account while developing alternative communicative strategies in ALS patients.

Retinal nerve fibre layer thickness changes in Alzheimer’s disease: Results from a 12-month prospective case series

PURPOSE To compare the 12-month peripapillary retinal nerve fibre layer (pRNFL) thickness change between AD patients and normal subjects. METHODS In this prospective case series, thirty-six patients with a diagnosis of mild to moderate AD and 36 age-matched control subjects were included. All the subjects underwent neuropsychological (MMSE, ADAS-Cog and CDR) and ophthalmological evaluation, including spectral domain optical coherence tomography (SD-OCT), at baseline and after 12 months. RESULTS Compared with controls, AD patients had a significant reduction of the total pRNFL thickness, as well as the pRNFL thickness of the inferior and superior quadrants (p=0.04, p=0.001, and p=0.01, respectively, adjusted for baseline pRNFL measurement, age, gender, and axial length). Correlation analysis showed a significant relationship between inferior pRNFL thickness change and ADAS-Cog scores change (r=-0.35, p=0.02) as well as CDR scores at 12 months (r=-0.39, p=0.008). CONCLUSIONS Compared with controls, AD patients had a significant reduction in pRNFL thickness over a period of 12 months. The pRNFL reduction was more prominent in the inferior quadrant and paralleled patients cognitive decline.

Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches

Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice.

Inappropriate Sexual Behaviors Among Community-Dwelling Patients with Dementia

OBJECTIVE Inappropriate sexual behaviors (ISBs) represent challenging and stressful manifestations of dementia and are highly burdening for patients, families, and healthcare providers. Nevertheless, ISBs have so far attracted limited clinical and scientific interest compared with other neuropsychiatric symptoms occurring in dementing illnesses. The authors aimed to systematically investigate the prevalence and characteristics of ISBs in a population of patients with dementia attending a memory clinic. METHODS In this cross-sectional study, individuals with dementia attending our memory clinic were consecutively enrolled between January 2015 and February 2016. Participating subjects underwent a detailed medical history collection and a comprehensive cognitive, functional, and neuropsychiatric assessment. The presence of ISBs (in the previous 30 days) was investigated by the adoption of an ad hoc questionnaire, administered to informants. A logistic regression model was carried out to identify sociodemographic and clinical variables associated with ISBs. RESULTS In the 195 patients (48.7% women) with dementia recruited for the study, ISBs were detected in 35 patients (17.9% of the total sample). The logistic regression model showed that male sex (OR: 5.14; 95% CI: 1.44-18.41) and anxiety (OR: 4.92; 95% CI: 1.44-16.84) were statistically significantly associated with the presence of ISBs. CONCLUSION ISBs represent common manifestations of dementing illnesses. Given the significant burden of ISBs on patients and families and the impact on care management, their occurrence should always be investigated in the clinical care of individuals with dementia. For this purpose, specific screening/assessment tools should be properly designed and validated.

Asymmetric responses to repetitive transcranial magnetic stimulation (rTMS) over the left and right primary motor cortex in a patient with lateralized progressive limb-kinetic apraxia.

Repetitive transcranial magnetic stimulation (5 Hz-rTMS, 10 stimuli, 120% resting motor threshold intensity, RMT) produces in healthy subjects a progressive facilitation of motor-evoked potential (MEP) amplitude probably through a short-term enhancement of cortical excitatory interneurones. We had the opportunity to investigate the effect of 5 Hz-rTMS delivered over the right and left primary motor cortex (M1) in a patient with limb-kinetic apraxia of the left hand and fingers and reduced cerebral perfusion in the fronto-parietal cortex of the right hemisphere documented by single-photon emission computed tomography scans. Changes in the MEP size during the trains and the RMT were measured and compared between the hemispheres. 5 Hz-rTMS was also delivered in a group of healthy subjects over both hemispheres in order to compare changes in the MEP size from the right and left M1. In the patient, 5 Hz-rTMS delivered over the left hemisphere elicited normal MEPs that progressively increased in size during the trains whereas 5 Hz-rTMS delivered over the right affected hemisphere failed to facilitate the MEP size. RMT was similar in both hemispheres. In healthy subjects, 5 Hz-rTMS delivered over either hemisphere elicited a similar, significant MEP size facilitation. Despite the limitations of a single case, our findings suggest an altered response to 5 Hz-rTMS over the M1 of the affected hemisphere. This asymmetric response correlated with the altered perfusion in the right hemisphere and the patients lateralized clinical manifestations of apraxia.

Attenuation of Choroidal Thickness in Patients With Alzheimer Disease: Evidence From an Italian Prospective Study.

Introduction: To compare the 12-month choroidal thickness (CT) change between Alzheimer disease (AD) patients and normal subjects. Methods: In this prospective, observational study, 39 patients with a diagnosis of mild to moderate AD and 39 age-matched control subjects were included. All the subjects underwent neuropsychological (Mini Mental State Examination, Alzheimer disease Assessment Scale-Cognitive Subscale, and the Clinical Dementia Rating Scale) and ophthalmological evaluation, including spectral domain optical coherence tomography, at baseline and after 12 months. CT was measured manually using the caliper tool of the optical coherence tomography device. Results: After 12 months, AD patients had a greater reduction of CT than controls (P⩽0.05, adjusted for baseline CT, age, sex, axial length, and smoking). Discussion: CT in patients with AD showed a rate of thinning greater than what could be expected during the natural course of aging.