Fabrizia D'Antonio

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.

Abnormalities of cortical neural synchronization mechanisms in patients with dementia due to Alzheimer's and Lewy body diseases: an EEG study

The aim of this retrospective exploratory study was that resting state eyes-closed electroencephalographic (rsEEG) rhythms might reflect brain arousal in patients with dementia due to Alzheimers disease dementia (ADD), Parkinsons disease dementia (PDD), and dementia with Lewy body (DLB). Clinical and rsEEG data of 42 ADD, 42 PDD, 34 DLB, and 40 healthy elderly (Nold) subjects were available in an international archive. Demography, education, and Mini-Mental State Evaluation score were not different between the patient groups. Individual alpha frequency peak (IAF) determined the delta, theta, alpha 1, alpha 2, and alpha 3 frequency bands. Fixed beta 1, beta 2, and gamma bands were also considered. rsEEG cortical sources were estimated by means of the exact low-resolution brain electromagnetic source tomography and were then classified across individuals, on the basis of the receiver operating characteristic curves. Compared to Nold, IAF showed marked slowing in PDD and DLB and moderate slowing in ADD. Furthermore, all patient groups showed lower posterior alpha 2 source activities. This effect was dramatic in ADD, marked in DLB, and moderate in PDD. These groups also showed higher occipital delta source activities, but this effect was dramatic in PDD, marked in DLB, and moderate in ADD. The posterior delta and alpha sources allowed good classification accuracy (approximately 0.85-0.90) between the Nold subjects and patients, and between ADD and PDD patients. In quiet wakefulness, delta and alpha sources unveiled different spatial and frequency features of the cortical neural synchronization underpinning brain arousal in ADD, PDD, and DLB patients. Future prospective cross-validation studies should test these rsEEG markers for clinical applications and drug discovery.

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.

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.

External validity of randomized controlled trials on Alzheimer’s disease: the biases of frailty and biological aging

To date, the external validity of randomized controlled trials (RCTs) on Alzheimer’s disease (AD) has been assessed only considering monodimensional variables. Nevertheless, looking at isolated and single characteristics cannot guarantee a sufficient level of appreciation of the AD patients’ complexity. The only way to understand whether the two worlds (i.e., research and clinics) deal with the same type of patients is to adopt multidimensional approaches more holistically reflecting the biological age of the individual. In the present study, we compared measures of frailty/biological aging [assessed by a Frailty Index (FI)] of a sample of patients with AD resulted eligible and subsequently included in phase III RCTs compared to patients referring to the same clinical service, but not considered for inclusion. The “RCT sample” and the “real world sample” were found to be statistically similar for all the considered sociodemographic and clinical variables. Nevertheless, the “real world sample” was found to be significantly frailer compared to the “RCT sample,” as indicated by higher FI scores [0.28 (SD 0.1) vs. 0.17 (SD 0.1); p < 0.001, respectively]. Moreover, when assessing the relationship between FI and age, we found that the correlation was almost null in the “RCT sample” (Spearman’s r = 0.01; p = 0.98), while it was statistically significant in the “real world sample” (r = 0.49; p = 0.02). The application of too rigid designs may result in the poor representativeness of RCT samples. It may even imply the study of a condition biologically different from that observed in the “real world.” The adoption of multidimensional measures capable to capture the individual’s biological age may facilitate evaluating the external validity of clinical studies, implicitly improving the interpretation of the results and their translation in the clinical arena.

Functional cortical source connectivity of resting state electroencephalographic alpha rhythms shows similar abnormalities in patients with mild cognitive impairment due to Alzheimer's and Parkinson's diseases

OBJECTIVE This study tested the hypothesis that markers of functional cortical source connectivity of resting state eyes-closed electroencephalographic (rsEEG) rhythms may be abnormal in subjects with mild cognitive impairment due to Alzheimers (ADMCI) and Parkinsons (PDMCI) diseases compared to healthy elderly subjects (Nold). METHODS rsEEG data had been collected in ADMCI, PDMCI, and Nold subjects (N = 75 for any group). eLORETA freeware estimated functional lagged linear connectivity (LLC) from rsEEG cortical sources. Area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification of Nold and MCI individuals. RESULTS Posterior interhemispheric and widespread intrahemispheric alpha LLC solutions were abnormally lower in both MCI groups compared to the Nold group. At the individual level, AUROC curves of LLC solutions in posterior alpha sources exhibited moderate accuracies (0.70-0.72) in the discrimination of Nold vs. ADMCI-PDMCI individuals. No differences in the LLC solutions were found between the two MCI groups. CONCLUSIONS These findings unveil similar abnormalities in functional cortical connectivity estimated in widespread alpha sources in ADMCI and PDMCI. This was true at both group and individual levels. SIGNIFICANCE The similar abnormality of alpha source connectivity in ADMCI and PDMCI subjects might reflect common cholinergic impairment.

Musical cognition in Alzheimer's disease: application of the Montreal Battery of Evaluation of Amusia

The aim of this study was to assess certain musical abilities in 30 patients with Alzheimers disease (AD) and 30 healthy controls by using the complete version of the Montreal Battery of Evaluation of Amusia (MBEA). This battery evaluates melodic (scale, contour, and interval) and temporal (rhythm and meter) perception of music and musical memory. We found that altered musical processing is a common feature in AD. Despite that, AD subjects show partially spared abilities for temporal organization of music, though not for melodic perception and musical memory. This peculiar dysfunctional pattern could depend on the neurodegenerative involvement of some specific areas for music perception and memory in the brains of AD patients. Further studies are needed to investigate the usefulness of additional musical tests like the MBEA on larger samples to confirm our preliminary data.

P20.6 Rivastigmine doesn't modify motor cortex synaptic plasticity in patients with Alzheimer's disease (AD): a repetitive transcranial magnetic stimulation (rTMS) study

amplitudes to the global/local switch cues. tDCS reduced left hemisphere beta (30 50 Hz) local switch cues oscillations following global cues and increased differences in beta between local and global cues. Anodal stimulation produced no significant EEG differences. Conclusions: These results represent the first successful use of tDCS to modulate attention and indicate and indicate a potential for tDCS as a possible therapeutic intervention for disorders of attention.

Abnormalities of Resting State Cortical EEG Rhythms in Subjects with Mild Cognitive Impairment Due to Alzheimer's and Lewy Body Diseases

The present study tested the hypothesis that cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms reveal different abnormalities in cortical neural synchronization in groups of patients with mild cognitive impairment due to Alzheimers disease (ADMCI) and dementia with Lewy bodies (DLBMCI) as compared to cognitively normal elderly (Nold) subjects. Clinical and rsEEG data in 30 ADMCI, 23 DLBMCI, and 30 Nold subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) score was matched between the ADMCI and DLBMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROCC) classified these sources across individuals. Compared to Nold, IAF showed marked slowing in DLBMCI and moderate in ADMCI. Furthermore, the posterior alpha 2 and alpha 3 source activities were more abnormal in the ADMCI than the DLBMCI group, while widespread delta source activities were more abnormal in the DLBMCI than the ADMCI group. The posterior delta and alpha sources correlated with the MMSE score and correctly classified the Nold and MCI individuals (area under the ROCC >0.85). In conclusion, the ADMCI and DLBMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test the clinical validity of these rsEEG markers.

ABNORMALITIES OF CORTICAL NEURAL SYNCHRONIZATION MECHANISMS IN SUBJECTS WITH MILD COGNITIVE IMPAIRMENT DUE TO ALZHEIMER’S AND PARKINSON’S DISEASES: AN EEG STUDY

with the results of the neurochemical dementia diagnostics (NDD) biomarkers in all cases (Ab1-42, Ab42/40 ratio (IBL International), Tau, and pTau181 (Fujirebio Europe, Ghent, Belgium)). Results: Intra-assay coefficients of variation were 1.2% and 0.8% for two CSF control samples (eight repetitions of each, sample dilution 1:2). Compared to the non-demented Controls (82.76 6.0 pg/mL), MCI-AD subjects and ADD patients had significantly increased concentrations of the CSF toxic Ab oligomers (88.4 6 4.5 pg/mL, p1⁄40.027, and 88.9 6 3.7 pg/mL, p1⁄40.016, respectively); there was no significant differences between MCI-AD and ADD subjects (p>0.9). The results remained significant after adjusting for age and sex of the subjects. Neither age nor sex (either unadjusted or adjusted for the concentrations of oligomeric Ab) significantly influenced the concentrations of oligomeric Ab. Conclusions: In line with amyloid hypothesis of AD, the results of this pilot study suggest increased concentrations of oligomeric Ab in the CSF of AD patients, already at the stage of MCI. Further studies are necessary to confirm our findings.