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We present the case of a patient with an atypical course of frontotemporal lobar degeneration (FTLD) complicated by the use of an anticholinergic drug. A 70-year-old patient, followed by psychiatrists for depression and behavioral disorders, received a diagnosis of dementia with Lewy bodies (DLB) at another Center due to auditory hallucinations, gait impairment, and tendency to fall. He was then admitted to our Memory Clinic Unit for behavioral disturbances, such as delusional thinking, auditory hallucinations, and memory complaints. At that time, the patient's therapy included Lorazepam, Quetiapine, Promazine, and Biperiden. The latter was immediately suspended for the absence of extrapyramidal signs and to avoid the anticholinergic cognitive side effects. A 18F-FDG PET showed a derangement of cortical metabolism with diffusely reduced activity, and limited areas of hyperactivity involving lateral frontal and lateral temporal inferior regions bilaterally. The patient underwent a series of exams, including neuropsychological tests, 123I-MIBG scintigraphy, cerebrospinal fluid examination, and genetic analysis. A second 18F-FDG PET showed an extensive remodulation of metabolic activity: relative higher concentration of the tracer in the prefrontal and inferior temporal cortex was no more detectable. Similarly, the diffuse reduced metabolic activity could not be traced anymore. Nonetheless, the metabolic activity still appeared reduced in the frontal lobe, in the anterior cingulate bilaterally, and in the anterior part of the hemispheric fissure. Taken together, clinical and neuroimaging features would point to a FTLD-like form. Furthermore, the diagnostic work-up was likely confounded by the anticholinergic drug on 18F-FDG PET, highlighting the importance of carefully checking the patient's pharmacology during the diagnostic process. [ABSTRACT FROM AUTHOR]

In the present work, we report the case of a patient presenting signs of Lewy body dementia (DLB) and frontotemporal dementia (FTD) throughout different phases of the disease. In January 2017, a 79-year-old right-handed living man was admitted to our Memory Clinic for the presence of behavioral disturbances and progressive cognitive decline. For the previous six years, he was monitored by other Neurological Clinics for the onset of extrapyramidal features. Indeed, through the first phase of the disease (2011-2014), the patient predominantly showed: extrapyramidal features, initial cognitive decline, sleep disturbances, and visual hallucinations, together with a reduced dopamine transporter uptake in basal ganglia at the DATscan, suggesting a diagnosis of DLB. In a second phase (2015-2017), while his extrapyramidal features remained substantially stable, his cognitive profile deteriorated, with an additional development of severe behavioral and neuropsychiatric disturbances. Again, a subsequent DATscan study was positive and slightly worse than the preceding one; however, the 18F-FDG PET showed reduced metabolic activity in the frontal and temporal lobes, with the occipital regions left spared. Genetic analysis revealed a hexanucleotide expansion in C9ORF72 (6//38 repeats; ITALSGEN NV <30). In conclusion, we report the case of a patient presenting, firstly, with probable DLB and, in a second phase, with predominant bvFTD features with stable parkinsonism. Even though some clinical and neuropsychological aspects can co-exist in different neurodegenerative diseases, we find such a significant intersection of clinical features to be fairly atypical. Moreover, what is challenging to define is whether the two clinical phenotypes are somehow lying on a continuum, or if they are two individual entities. [ABSTRACT FROM AUTHOR]

Background: Frailty is a condition which is characterized by a reduction in the homeostatic reserves of the individual and which entails an increased vulnerability to stressful endogenous and exogenous agents. The Frailty Index (FI), proposed by Rockwood, was designed following an accumulation of deficits model: the greater the number of deficits in a given individual, the greater the degree of frailty.Objective: The aim of this study was to verify the existence of associations between FI and cerebral atrophy.Methods: The TREDEM Register (Treviso Dementia) provided retrospective observational data from 1,584 patients. The FI was calculated based on 50 variables comprising diseases, disability, behavioral disturbances, and blood chemistry parameters. The severity of atrophy in the cortical and subcortical regions, such as the amplitude of the lateral ventricles, were detected by computerized axial tomography (CAT). Multiple logistic regression models using the stepwise backward method were used to analyze possible associations between FI and atrophy.Results: For each increment of one hundredth of the FI, the probability of cortical atrophy increases by 2%. The female gender is a protective factor for cortical and subcortical atrophy. At each increase of one percent of the FI, the probability of a severe degree of cortical atrophy increases by 3%. The FI was significantly associated with frontal and temporal cortical atrophy. The relationship between overall subcortical atrophy and the FI was not significant, whereas it was the one with the severe degree of subcortical atrophy. The FI is significantly associated with the atrophy of the peri-insular subcortical region. Similar associations were found considering only demented patients.Conclusion: The FI is associated with the presence, degree, and some localization of cerebral atrophy in a population of cognitive-decline patients. [ABSTRACT FROM AUTHOR]

Background: The pharmacological treatment of Alzheimer's disease (AD) is based largely on cholinesterase inhibitors (ChEI).Objective: To investigate whether or not some non-pharmacological and contextual factors measured prior to starting treatment such as past occupation, lifestyles, marital status, degree of autonomy and cognitive impairment, living alone or with others, and the degree of brain atrophy are associated with a better response to ChEI treatment.Methods: Eighty-four AD and six AD with cerebrovascular disease (AD + CVD) outpatients of Treviso Dementia (TREDEM) Registry, with an average cholinesterase inhibitors treatment length of four years, were considered. The outpatients had undergone a complete evaluation and some non-pharmacological and contextual factors were collected. We defined responder a patient with a delta score T0 - T1 equal or inferior to 2.0 points per year of MMSE and a non-responder a patient with a delta score T0 - T1 superior to 2.0 points per year. In order to identify hidden relationships between variables related to response and non-response, we use a special kind of artificial neural network called Auto-CM, able to create a semantic connectivity map of the variables considered in the study.Results: A higher cognitive profile, a previous intellectual occupation, healthier lifestyles, being married and not living alone, a higher degree of autonomy, and lower degree of brain atrophy at baseline resulted in affecting the response to long-term ChEI therapy.Conclusion: Non-pharmacological and contextual factors appear to influence the effectiveness of treatment with ChEI in the long term. [ABSTRACT FROM AUTHOR]

An association between frailty and vascular brain damage (VBD) has been described in older adults. However, most studies have identified frailty according to the phenotypic model. It is less clear whether frailty, operationalized as an accumulation of health deficits, is associated with the presence and severity of VBD. The present study was therefore undertaken to verify whether a 50-item frailty index (FI) is related to VBD in a large and relatively unselected cohort of attendees of a memory clinic. The TREDEM (Treviso Dementia) registry includes retrospective observational data of 1584 participants. A modified FI was calculated from 50 variables comprising diseases, disability, behavioral disorders, and blood biochemistry. The presence and severity of VBD, including leukoaraiosis, lacunes, larger infarctions and the hierarchical vascular rating scale (HVRS), were determined based on brain computerized tomography imaging. Multiple logistic regression models were built according to the stepwise method. Mean age of the 1584 participants was 79.6 ± 7.5 years and 1033 (65.2 %) were females. The average number of health deficits was 11.6 ± 6.2, corresponding to an FI of 0.23 ± 0.12 (range: 0.00–0.56). Each 0.01-point increase in the FI was associated with an increased probability of leukoaraiosis (+2.3 %) and severe leukoaraiosis (+5 %), lacunas in the basal ganglia (+1.73 %), occipital lobes (+2.7 %), parietal lobes (+3 %), frontal lobes (+3.6 %), temporal lobes (+4.2 %), and thalamus (+4.4 %). Moreover, an increase of 0.01 points in the FI was associated with a 3.1 % increase in the probability of HVRS score (≥2). An FI based on routine clinical and laboratory variables was associated with the presence, degree, and some localizations of VBD in a population of older adults with cognitive decline. This frailty assessment tool may therefore be used to identify individuals at risk of developing cerebrovascular disease and, consequently, to implement strategies for vascular risk factor control. • The frailty index (FI) provides a comprehensive overview of an individual's vulnerability. • The FI is positively correlated with the severity of vascular brain damage. • Study participants were relatively unselected outpatients and may therefore be representative of a "real-world" population. • The FI may be used to identity older adults at risk of cerebrovascular disease. [ABSTRACT FROM AUTHOR]

Background: The Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment has been developed to predict mortality in hospitalized elderly patients. The Treviso Dementia (TREDEM) Study is an observational prospective cohort study of 1,364 outpatients evaluated at the Cognitive Impairment Center in Treviso, Italy from 2000 to January 2010. Objective: To use the MPI in the TREDEM outpatient setting to assess the correlation of MPI with mortality and hospitalizations for acute cases that occurred after the date of assessment. Methods: MPI was consecutively applied to the last 340 of 1,364 outpatients who were evaluated at the Center from 2008 to January 2010, after the first publication of MPI index in 2008. Participants' mortality was verified by linking the cohort with Registries of Municipalities, National Register of Revenue Authorities, and Nominal Register of Causes of Death. Data about hospitalizations for acute cases that occurred within 12 months after the date of assessment were obtained from all Italian hospitals. A Cox regression method was used to investigate the effect of MPI upon mortality and hospitalizations, also considering confounder factors such as age and gender. Results: 114 men and 226 women, aged 52.1-99 years (mean age 80.4 years), were studied and had an MPI mean of 0.41. On 15 February 2013, 100 were deceased, and average hospitalizations for acute cases were 0.3, days 3.8. For MPI scores between 0 and 1, the increase in the probability of death was more than nine times (odds: 9.53 p = 0.0002) and of hospitalization was more than six times (odds: 6.50, p = 0.0079). Conclusion: MPI discloses the risk of death and of hospitalizations for acute cases in outpatients affected by cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: The role of folate and homocysteine in brain atrophy associated with Alzheimer's disease is not completely understood. Objective: The aim of this study was to investigate the relationships between serum folate and homocysteine levels and the degree of cortical-subcortical and hippocampal atrophy in a first relatively preliminary sample of the Treviso Dementia (TREDEM) study using a potent data mining method. Methods: Physiological data, biochemical parameters, clinical assessment data, brain atrophy severity assessed with CT scans, and neuropsycological and disability data were assessed in a group of 232 outpatients (93 men and 139 women, aged 40.2-100 years) enrolled in the TREDEM study carried out in Treviso (Italy). A semantic connectivity map obtained through the Auto-CM system, a fourth generation artificial neural network (ANN), was used to offer some insight regarding the complex biological connections between the studied variables and the degree of brain atrophy. Results: Close associations between low serum folate levels and severe cortical-subcortical atrophy along with severe hippocampal atrophy measured by the width of the temporal horns of lateral ventricles were found. We also showed an association between high homocysteine levels and severe cortical-subcortical and hippocampal atrophy. Conclusion: The role of folate, which is inversely associated with the severity of brain atrophy, was confirmed. Our results also confirm the association between high homocysteine levels and severe cortical-subcortical and hippocampal atrophy. Auto-CM ANN is able to highlight associations sometimes visible only in longitudinal studies through intelligent data mining of a cross-sectional study. [ABSTRACT FROM AUTHOR]

Background: An 82-year-old right-handed man, a retired teacher, reported the occurrence, three years earlier, of difficulties in moving his left arm and foot, tremor in his left hand, and gestures of the left upper limb that appeared to be independent of the patient's will., Objective: We describe an unusual case of corticobasal syndrome (CBS) showing disease-associated biomarkers of dementia with Lewy bodies (DLB)., Methods: Clinical, neuropsychological, imaging, and biomarker evaluations were conducted, including tau and amyloid-β levels in the cerebrospinal fluid (CSF) and a RT-QuIC assay for α-synuclein both in the CSF and olfactory mucosa (OM), as well as a QEEG assessment., Results: The patient presented resting tremor, mild extrapyramidal hypertonus, mild bradykinesia on the left side, and severe apraxia on the left upper limb. Brain MRI showed a diffuse right hemisphere atrophy which was prominent in the posterior parietal and temporal cortices, and moderate in the frontal cortex and the precuneus area. 18 F-FDG PET imaging showed reduced glucose metabolism in the right lateral parietal, temporal, and frontal cortices with involvement of the right precuneus. The putamen did not appear to be pathological at DaTQUANT. Neuropsychological tests showed memory and visual-perceptual deficits. CSF tau and amyloid measurements did not show clear pathological values. RT-QuIC for α-synuclein in CSF and OM samples were positive. The QEEG analysis showed a pre-alpha dominant frequency in posterior derivations, typical of early stages of DLB., Conclusion: Although in the present patient the clinical diagnosis was of probable CBS, unexpectedly positive biomarkers for DLB suggested the co-presence of multiple pathologies., Competing Interests: The authors have no conflict of interest to report., (© 2022 – The authors. Published by IOS Press.)

Background: A 57-year-old right-handed man was admitted to the Treviso Memory Clinic due to the presence of memory forgetfulness, repetition of the same questions, episodes of confusion, initial difficulties in performing complex tasks and easy distraction over the past two years, as well as recurrent and never-happened-before car accidents., Objective: We report a peculiar case of an early onset Alzheimer's disease (AD) with an unusual symptomatology, apparently not fitting in any of the categorized atypical forms of AD nor being representative of a typical amnestic AD., Methods: The patient underwent a neuropsychological, structural, and metabolic cerebral evaluation by MRI and 18 F-FDG PET, together with the search for cerebral amyloid (amyloid PET), a genetic testing for dementia related genes and the dosage of CSF protein biomarkers of neurodegenerative conditions., Results: We observed a convergence of predominant frontal (dysexecutive, verbal disinhibition) and posterior (visuospatial) features of cognitive impairment. Structural MRI sequences showed subarachnoid spaces of the vault enlarged in the fronto-parietal region with anterior and posterior cortical atrophy. The hippocampus appeared preserved. The 18 F-FDG PET scans showed hypometabolism in the prefrontal, lateral temporal, posterior parietal, and occipital regions bilaterally. The 18 F-Flutemetamol scan showed a diffused uptake of the amyloid tracer at the cerebral cortex. CSF biomarkers were compatible with Alzheimer's disease (AD)., Conclusion: This case report presented with clinical phenotypic aspects atypical of AD, both frontal and posterior, never described as concomitant in the most accredited criteria for atypical AD, and appeared therefore more atypical than each of the atypical AD phenotypes already reported., Competing Interests: The authors have no conflict of interest to report., (© 2021 – The authors. Published by IOS Press.)

Background: Frailty is a condition which is characterized by a reduction in the homeostatic reserves of the individual and which entails an increased vulnerability to stressful endogenous and exogenous agents. The Frailty Index (FI), proposed by Rockwood, was designed following an accumulation of deficits model: the greater the number of deficits in a given individual, the greater the degree of frailty., Objective: The aim of this study was to verify the existence of associations between FI and cerebral atrophy., Methods: The TREDEM Register (Treviso Dementia) provided retrospective observational data from 1,584 patients. The FI was calculated based on 50 variables comprising diseases, disability, behavioral disturbances, and blood chemistry parameters. The severity of atrophy in the cortical and subcortical regions, such as the amplitude of the lateral ventricles, were detected by computerized axial tomography (CAT). Multiple logistic regression models using the stepwise backward method were used to analyze possible associations between FI and atrophy., Results: For each increment of one hundredth of the FI, the probability of cortical atrophy increases by 2%. The female gender is a protective factor for cortical and subcortical atrophy. At each increase of one percent of the FI, the probability of a severe degree of cortical atrophy increases by 3%. The FI was significantly associated with frontal and temporal cortical atrophy. The relationship between overall subcortical atrophy and the FI was not significant, whereas it was the one with the severe degree of subcortical atrophy. The FI is significantly associated with the atrophy of the peri-insular subcortical region. Similar associations were found considering only demented patients., Conclusion: The FI is associated with the presence, degree, and some localization of cerebral atrophy in a population of cognitive-decline patients.