RESUMO
Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% of middle-age-onset dementias and entails a social, economic, and emotional burden for the patients and caregivers. It is characterised by a (at least initially) selective degeneration of the frontal and/or temporal lobe, generally leading to behavioural alterations, speech disorders, and psychiatric symptoms. Despite the recent advances, given its extreme heterogeneity, an overview that can bring together all the data currently available is still lacking. Here, we aim to provide a state of the art on the pathogenesis of this disease, starting with established findings and integrating them with more recent ones. In particular, advances in the genetics field will be examined, assessing them in relation to both the clinical manifestations and histopathological findings, as well as considering the link with other diseases, such as amyotrophic lateral sclerosis (ALS). Furthermore, the current diagnostic criteria will be explored, including neuroimaging methods, nuclear medicine investigations, and biomarkers on biological fluids. Of note, the promising information provided by neurophysiological investigations, i.e., electroencephalography and non-invasive brain stimulation techniques, concerning the alterations in brain networks and neurotransmitter systems will be reviewed. Finally, current and experimental therapies will be considered.
Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Doenças Neurodegenerativas , Doença de Pick , Pessoa de Meia-Idade , Humanos , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/terapia , Demência Frontotemporal/patologia , Esclerose Lateral Amiotrófica/patologia , Lobo Temporal/patologiaRESUMO
In this post-hoc analysis of the AXEPT study, 855 patients were analyzed, 544 (63.6%) females. The mean (± SD) MMSE score in women vs men was 20.8 ± 2.6 vs. 21.2 ± 2.5; p = 0.0087, and women were more likely affected by psychiatric disorders (n = 76, 14.0% women vs. n = 21, 6.8% men; p = 0.0015). Men were mainly assisted by their wives (n = 207, 66.6%), women mainly by their daughters (n = 243, 44.7%) and only in a minority of cases by their husbands (n = 92, 16.9%). Women less frequently cohabited with their caregivers than men (n = 233, 43.1% vs. n = 240, 77.9%, p < 0.0001), and received less daily time of caregiving (mean (± SD): 10.0 ± 7.2 vs. 15.2 ± 8.2; p < 0.0001). No gender differences were highlighted in compliance to treatment and caregiver satisfaction, while gender differences in caregiving were found at disadvantage of women affected by more severe cognitive and psychiatric conditions.
Assuntos
Doença de Alzheimer , Masculino , Humanos , Feminino , Doença de Alzheimer/psicologia , Doença de Alzheimer/terapia , Cuidadores/psicologia , Vida Independente , Núcleo Familiar , Satisfação PessoalRESUMO
Background/Objectives: Cognitive impairment in spinocerebellar ataxia patients has been reported since the early-disease stage. We aimed to assess cognitive differences in SCA1 and SCA2 patients. Methods: We performed neuropsychological (NPS) and neurophysiological (auditory event-related potentials, aERPs) assessments in 16 SCA1 and 18 SCA2 consecutive patients. Furthermore, clinical information (age at onset, disease duration, motor disability) was collected. Results: NPS tests yielded scores in the normal range in both groups but with lower scores in the Frontal Assessment Battery (p < 0.05) and Visual Analogue Test for Anosognosia for motor impairment (p < 0.05) in SCA1, and the Trail Making Test (p < 0.01), Raven's progressive matrices (p < 0.01), Stroop (p < 0.05), and emotion attribution tests (p < 0.05) in SCA2. aERPs showed lower N100 amplitude (p < 0.01) and prolonged N200 latency (p < 0.01) in SCA1 compared with SCA2. Clinically, SCA2 had more severe motor disability than SCA1 in the Assessment and Rating of Ataxia Scale. Conclusions: SCA2 showed more significant difficulties in attentional, visuospatial, and emotional function, and greater motor impairment. In contrast, SCA1 showed less cognitive flexibility/phasic ability, probably affected by a more severe degree of dysarthria. The same group revealed less neural activity during nonconscious attentional processing (N100-N200 data), suggesting greater involvement of sensory pathways in discriminating auditory stimuli. NFS did not correlate with NPS findings, implying an independent relationship. However, the specific role of the cerebellum and cerebellar symptoms in NPS test results deserves more focus.
RESUMO
Cerebral venous thrombosis (CVT) is a rare cause of stroke, particularly in young adults. Several known thrombophilic conditions may lead to an increased CVT risk. Interestingly, few cases in the literature have reported an association between CVT and thyrotoxicosis. Here, we describe the case of a young woman with CVT and concomitant thyrotoxicosis, without any other known prothrombotic conditions. We also performed a literature review of CVT cases and hyperthyroidism, searching for all articles published in peer-reviewed journals. We identified 39 case reports/case series concerning patients with CVT associated with thyrotoxicosis, highlighting, in most cases, the association with additional known prothrombotic factors. We then discussed the possible mechanisms by which hyperthyroidism could underlie a pro-coagulative state resulting in CVT. Thyroid disease might be a more common prothrombotic risk factor than expected in determining CVT. However, in most cases, a coexistence of multiple risk factors was observed, suggesting a multifactorial genesis of the disorder. We hope that this work may alert clinicians to consider thyrotoxicosis as a potential risk factor for CVT, even in patients who apparently have no other pro-coagulative conditions.
RESUMO
PURPOSE: Cholinesterase inhibitors are commonly prescribed to patients with Alzheimer's disease (AD) to enhance cholinergic neurotransmission. Differential response to these treatments has been observed, and claims have been made that individual genetic variants may influence the pharmacokinetic and pharmacodynamic properties of these drugs. Here we assess the effects of genetic variation at two loci involved in the activity of cholinesterase inhibitors on longitudinal clinical change in AD patients being treated with donepezil, galantamine, and rivastigmine. METHODS: This was an open study in which 171 Italian AD patients treated with donepezil (n = 92), galantamine (n = 33), or rivastigmine (n = 46) were enrolled. Response to treatment was quantified by grading the patient's cognitive state (Mini-Mental State Examination) and the patient's ability to perform normal daily activities (Activities of Daily Living, Instrumental Activities of Daily Living) at baseline and after 6 and 12 months of treatment. Genetic variation was comprehensively characterized and analyzed at two loci: CYP2D6, which is involved in donepezil and galantamine metabolism, and BCHE, which codes for an enzyme (butyrylcholinesterase) which is both target and metabolizer of rivastigmine. APOE (coding for apolipoprotein E), which is associated with the risk of AD and inefficacy of specific AD treatments, was genotyped to control for patient stratification. The influence of the CYP2D6 and BCHE genotype on clinical changes after 12 months was evaluated by several tests of association. RESULTS: After 1 year of treatment, 29, 12, and 12 of the patients receiving donepezil, galantamine, and rivastigmine, respectively, showed a cognitive decrement, while eight patients interrupted the therapy before 12 months of treatment. No significant differences between the three treatments were observed in terms of response and tolerability. Non-responders show a higher proportion of BCHE and CYP2D6 mutated alleles, but genetic variation at the two loci was not a reliable predictor of clinical changes in AD patients treated with cholinesterase inhibitors. CONCLUSIONS: Individualized therapy based on CYP2D6 and BCHE genotypes is unlikely to be beneficial for treating Alzheimer's disease patients in routine clinical practice.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase/genética , Inibidores da Colinesterase/uso terapêutico , Cognição/efeitos dos fármacos , Citocromo P-450 CYP2D6/genética , Variação Genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/enzimologia , Doença de Alzheimer/fisiopatologia , Apolipoproteínas E/genética , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/efeitos adversos , Inibidores da Colinesterase/farmacocinética , Donepezila , Feminino , Galantamina/administração & dosagem , Galantamina/efeitos adversos , Galantamina/farmacocinética , Galantamina/uso terapêutico , Estudos de Associação Genética , Genótipo , Humanos , Indanos/administração & dosagem , Indanos/efeitos adversos , Indanos/farmacocinética , Indanos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fenilcarbamatos/administração & dosagem , Fenilcarbamatos/efeitos adversos , Fenilcarbamatos/farmacocinética , Fenilcarbamatos/uso terapêutico , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Piperidinas/farmacocinética , Piperidinas/uso terapêutico , Rivastigmina , Resultado do TratamentoRESUMO
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative pathology covering about 70%of all cases of dementia. Adenosine, a ubiquitous nucleoside, plays a key role in neurodegeneration, through interaction with four receptor subtypes. The A2A receptor is upregulated in peripheral blood cells of patients affected by Parkinson's and Huntington's diseases, reflecting the same alteration found in brain tissues. However, whether these changes are also present in AD pathology has not been determined. OBJECTIVE: In this study we verified any significant difference between AD cases and controls in both brain and platelets and we evaluated whether peripheral A2A receptors may reflect the status of neuronal A2A receptors. METHODS: We evaluated the expression of A2A receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, in postmortem AD patients and control subjects, through [3H]ZM 241385 binding experiments. The same analysis was performed in peripheral platelets from AD patients versus controls. RESULTS: The expression of A2A receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, revealed a density (Bmax) of 174±29, 219±33, and 358±84âfmol/mg of proteins, respectively, in postmortem AD patients in comparison to 104±16, 103±19, and 121±20âfmol/mg of proteins in controls (pâ<â0.01). The same trend was observed in peripheral platelets from AD patients versus controls (Bmax of 214±17 versus 95±4âfmol/mg of proteins, respectively, pâ<â0.01). CONCLUSION: AD subjects show significantly higher A2A receptor density than controls. Values on platelets seem to correlate with those in the brain supporting a role for A2A receptor as a possible marker of AD pathology and drug target for novel therapies able to modify the progression of dementia.
Assuntos
Doença de Alzheimer/sangue , Biomarcadores/sangue , Plaquetas/metabolismo , Córtex Cerebral/metabolismo , Receptor A2A de Adenosina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Regulação para CimaRESUMO
Melatonin has been reported to reduce preoperative anxiety. We performed this study to compare preoperative anxiety in elderly patients receiving melatonin (M) or placebo (P). Anxiety was measured in patients aged >65 yr by a numerical rating scale (range, 0-10). Each patient was randomized to receive M 10 mg or P orally: 71 patients were in group P and 67 in group M. The median (quartiles) anxiety level was 5 (2-8) before and 3 (1-7) 90 min after premedication in group M and 5 (3-6) and 3 (1-5) in group P, respectively. M and P reduce anxiety in elderly patients to a similar degree.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Melatonina/uso terapêutico , Medicação Pré-Anestésica , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Cuidados Pré-OperatóriosRESUMO
BACKGROUND/AIMS: According to experimental data, a transdermal application is preferred by caregivers of Alzheimer's disease (AD) patients compared with oral medications. The AXEPT study compared compliance to treatment among community-dwelling patients with mild-to-moderate AD treated with transdermal application compared to oral medications and caregiver satisfaction in a real clinical setting. METHODS: Data from 45 memory clinics in Italy were collected between September 8, 2010 and January 31, 2011. Compliance to treatment and caregiver satisfaction were measured using the Caregiver Medication Interview. RESULTS: A total of 855 AD patients and their caregivers participated in the study. Nearly 80% of caregivers of patients on patch were not concerned about adherence to treatment compared with 64% of caregivers of patients on oral drugs. Among caregivers of patients on patch, 94% did not report any difficulties in remembering to administer treatment compared with 73% of caregivers of patients on oral medications. The highest level of compliance and satisfaction was reported by caregivers of patients on transdermal application. CONCLUSION: Caregivers of patients treated with a transdermal application appeared to be more satisfied and reported a higher level of compliance than caregivers of patients receiving anti-AD oral medications.