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BACKGROUND: Mild Cognitive Impairment (MCI) is a heterogeneous condition characterised by cognitive changes that do not affect everyday functioning and may represent a predementia phase. Research on the neuroanatomical correlates of cognitive tests used to diagnose MCI is heterogeneous and has mainly focused on elderly populations of patients with MCI, usually well above the age of 65. However, the effect of ageing on brain structure is known to be substantial and to affect brain-behaviour associations in older people. We explored the brain correlates of different cognitive tests in a group of young-onset MCI (i.e., with symptoms onset before the age of 65) to minimise the effect of ageing on brain-behaviour associations. METHODS: Patients with a clinical diagnosis of young-onset MCI underwent extensive cognitive assessment and multimodal Magnetic Resonance Imaging (MRI) including high-resolution T1-weighted and Diffusion Tensor Imaging (DTI) sequences. Their scores on cognitive tests were related to measures of grey matter (GM) density and white matter (WM) integrity using, respectively, Voxel Based Morphometry (VBM) and Tract-Based Spatial Statistics (TBSS). RESULTS: 104 young-onset MCI were recruited. VBM and TBSS whole-brain correlational analyses showed that between-subject variability in cognitive performance was significantly associated with regional variability in GM density and WM integrity. While associations between cognitive scores and focal GM density in our young-onset MCI group reflected the well-known lateralization of verbal and visuo-spatial abilities on the left and right hemispheres respectively, the associations between cognitive scores and WM microstructural integrity were widespread and diffusely involved most of the WM tracts in both hemispheres. CONCLUSIONS: We investigated the structural neuroanatomical correlates of cognitive tests in young-onset MCI in order to minimise the effect of ageing on brain-behaviour associations.
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Disfunción Cognitiva , Sustancia Blanca , Humanos , Anciano , Imagen de Difusión Tensora/métodos , Disfunción Cognitiva/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Imagen por Resonancia Magnética , Pruebas NeuropsicológicasRESUMEN
The number of people with dementia is increasing worldwide. Two main approaches have been adopted to identify subjects with Alzheimer's disease (AD): the neuropsychological evaluation and the identification of biomarkers of AD. The first method is less invasive and easier to perform. This study assesses the psychometric properties of COGITAB, a novel web application d esigned to be sensitive to the subtle cognitive changes distinctive of the early Mild Cognitive Impairment (MCI) and the preclinical phase of AD. We enrolled 518 healthy controls, classified according to several risk factors and the presence of a family history of dementia. The participants were given COGITAB after a neuropsychological screening. The COGITAB Total Score (TS) was significantly affected by age and years of education. Acquired risk factors and family history of dementia significantly impacted only the COGITAB total execution time (TET), not the TS. This study provides normative data for a newly developed web application. Control subjects with acquired risk factors performed slower, giving an important role to the TET recording. Further studies should examine the ability of this new technology to discriminate between healthy subjects and subjects with initial cognitive decline, even when not detected by standard neuropsychological assessments.
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Severe non-infectious or non-haemorrhagic brain edema surrounding the electrode represents a rare complication of subthalamic nucleus deep brain stimulation (STN-DBS) surgery. The aim of this study is to report three patients with advanced Parkinson's Disease (PD) who developed symptomatic brain edema after STN-DBS surgery treated with intravenous steroids with a specific profile of reversible cognitive alterations. Patients were both assessed with a comprehensive neuropsychological battery including attention, memory, visuo-spatial and executive tasks. They were also briefly assessed for emotional and behavioural alterations, and for possible limitations in the activities of daily living. Normative data for an Italian population were available for all neuropsychological tests. The patients were firstly assessed before the surgery (baseline) as soon as they became symptomatic for the post-surgery edema and a few more times in follow-up up to ten months. In all patients we observed the resolution of cognitive deficits within six months after surgery with the corresponding reabsorption of edema at brain CT scans. The appearance of post-DBS edema is a fairly frequent and clinically benign event. However, in some rare cases it can be very marked and lead to important clinical-albeit transient-disturbances. These events can compromise, at least from a psychological point of view, the delicate path of patients who undergo DBS and can prolong the post-operative hospital stay. In this setting it could be helpful to perform a brain CT scan in 2-3 days with the aim of detecting the early appearance of edema and treating it before it can constitute a relevant clinical problem.
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Mutations in presenilin 1 gene (PSEN1) are the most common causes of autosomal dominant early-onset Alzheimer's disease (EOAD). We report a novel PSEN1 mutation (I213S) that was discovered in an Italian patient with a family history of early-onset dementia, who developed a slowly progressive cognitive decline since the age of 40 years. Clinical investigations, including neuropsychological assessment, brain MRI and 18-fluorodeoxyglucose PET, as well as cerebrospinal fluid biomarkers, supported the diagnosis of EOAD. Genetic studies identified a novel missense mutation at codon 213 (I213S). Three other mutations at the same codon have been described in association with EOAD. Previous in silico, in vitro and in vivo studies indicated that these mutations affect the functional properties of γ-secretase and are most likely pathogenic. In silico algorithms suggested that even the I213S mutation has similar deleterious effects on PSEN1 structure and function. Overall, these data strongly support a role of hotspot site for the codon 213 of PSEN1, and provide evidence that the genetic variants located on this site cause EOAD.
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Enfermedad de Alzheimer , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Codón/genética , Humanos , Mutación/genética , Presenilina-1/genética , Presenilina-2/genéticaRESUMEN
Semantic variant primary progressive aphasia (svPPA) is a rare neurodegenerative disease characterized by a progressive loss of semantic knowledge. Patients with svPPA show anomia, impaired word comprehension, poor object recognition, and difficulties in retrieving semantic information. svPPA is also a unique "natural" model that allows clinicians and cognitive neuroscientists to study the organization of semantic memory because only semantic knowledge is affected in the initial period of the disease, with relative sparing of other cognitive domains. In the clinical practice, semantic memory is commonly tested only with verbal tests. The aim of the present study was to preliminary test a new Multimodal Semantic Battery developed in our laboratory, which comprised 11 subtests designed to assess the semantic knowledge of multiple items via all input modalities. The battery was administered twice, over four years, to a patient diagnosed with svPPA. We found that when extensively tested with multiple tests, in some cases, he was still able to recall semantic features of the items that otherwise would not have emerged with standard semantic tests. These results are discussed for the clinical practice: monitoring semantic memory through all modalities in a practical and reliable way could be useful for both clinicians and experimental researchers to better investigate the breakdown of semantic knowledge.
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Afasia Progresiva Primaria/diagnóstico , Afasia Progresiva Primaria/fisiopatología , Formación de Concepto/fisiología , Progresión de la Enfermedad , Recuerdo Mental/fisiología , Pruebas Neuropsicológicas , Humanos , SemánticaRESUMEN
OBJECTIVE: A case report of a 74-year-old male presenting with an atypical multimodal semantic impairment. The patient was diagnosed with Waldenström macroglobulinemia (WM) for which he received allogeneic bone marrow transplantation (BMT) due to disease progression. Following BMT, he developed a sudden onset of semantic difficulties that have remained unchanged for eight years. No other cognitive functions have been affected and his activities of daily living remain fully preserved. METHOD: The patient was assessed at our neuropsychology unit with six neuropsychological evaluations over an 8-years follow-up period following BMT. Additional semantic tests were administered during the last three evaluations. Four MRI scans (at age 62, 66, 69 and 74) and 18F-FDG PET (at age 74) were obtained. RESULTS: The patient presents a multimodal semantic impairment, including naming impairment, visual agnosia, prosopoanomia, associative prosopagnosia, topographical disorientation and impaired retrograde memory for public events. MRI scans and 18F-FDG PET revealed bilateral symmetrical atrophy (temporal > frontal) and inferior bilateral temporal lobe hypometabolism, respectively. Neuroradiological examination was unremarkable prior to BMT. CONCLUSION: Clinical diagnosis remains a challenge given the focal and stable nature of his deficits. We hypothesize that the BMT procedure might have resulted in the temporal lobe damage and subsequent semantic impairment. We recommend obtaining a thorough neuropsychological evaluation of patients who receive allogenic BMT, both prior to and following transplant.
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Trasplante de Médula Ósea/métodos , Pruebas Neuropsicológicas/normas , Trasplante Homólogo/métodos , Macroglobulinemia de Waldenström/terapia , Anciano , Humanos , Masculino , Semántica , Macroglobulinemia de Waldenström/patologíaRESUMEN
Introduction: Anti-leucine-rich glioma-inactivated 1 limbic encephalitis (LGI1-LE) is an autoimmune disorder associated with antibodies to voltage-gated potassium channels (VGKC). It is a non-paraneoplastic and partially reversible encephalitis that can be diagnosed via serological testing. Untreated LGI1-LE can be associated with neurocognitive as well as neuropsychiatric sequelae. Here we report the neuropsychological and clinical profile of a patient with LGI1-LE following three different treatment approaches: plasmapheresis (PA), intravenous immunoglobulin (IVIG), and corticosteroids (CO). Method: We investigated our patient with 10 neuropsychological evaluations obtained over a 9-year follow-up period. Multiple MRI scans, EEG recordings, neurological examinations, and serum tests were also obtained. Results: The neurocognitive profile of our patient was characterized by long-term memory impairment (verbal and visual-spatial), and deficits in aspects of executive functioning and language. Neuropsychiatric symptoms of depression and anxiety were noted intermittently. Conclusions: Non-specific treatment prior to diagnosis had marginal effects on neurocognitive profile, neuropsychiatric symptoms, or control of epileptic seizure. In contrast, specific treatments for LGI1-LE following diagnosis resulted in neurocognitive improvement and epileptic control. Among the three treatments, IVIG and CO had the most beneficial impact on neurocognitive status, likely due to the continuity of administration.
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Disfunción Cognitiva , Epilepsia , Péptidos y Proteínas de Señalización Intracelular/inmunología , Encefalitis Límbica , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Epilepsia/etiología , Epilepsia/fisiopatología , Función Ejecutiva/fisiología , Estudios de Seguimiento , Humanos , Lenguaje , Encefalitis Límbica/complicaciones , Encefalitis Límbica/inmunología , Imagen por Resonancia Magnética , Memoria a Largo Plazo/fisiología , ConvulsionesRESUMEN
BACKGROUND: Present opinions regarding developmental delay of children conceived with intracytoplasmic sperm injection (ICSI) are variable and without consensus. METHODS: We compared developmental outcome at 1 and 2 years of 50 children conceived by ICSI with 51 spontaneously conceived children. Assessments were performed using the Bayley Scales of Infant Development for motor and mental development and quality of behavior, and the CARE-Index for the quality of parent-child interaction. RESULTS: No difference was present in the motor and mental development of study and control groups, as assessed by the Bayley Scales. However, 1-year-old ICSI children had lower Behavioral Index scores than controls in the "Motor Quality" item (p = 0.04). Regarding interaction with parents, ICSI families had lower "father cooperation" CARE-Index scores (p = 0.02) and lower sensitivity scores (p = 0.007). No significant differences were present between study and control groups for the 2-year-old children. CONCLUSIONS: ICSI conceived children develop normally. When assessed by the Bayley Scales of Infant Development and the CARE-Index, the differences in quality of development and social interaction observed at 1 year of age had no negative effect on the overall level of development, and appeared to be related to developmental processes of the entire family unit rather than to ICSI-related biological effects. Observed differences dissipated with familial adaptation and were not observed at 2 years of age.