Francesca Gnoato

Adherence in liver transplant recipients

Adherence to a medical regimen has been defined as the extent to which a patients behavior coincides with clinical prescriptions. In liver transplant patients, adherence to immunosuppressive therapy and to medical indications in general is crucial for short‐ and long‐term outcomes. Nonadherence to immunosuppression carries a risk of graft rejection and potential graft loss, whereas nonadherence to general medical indications (eg, avoiding alcohol intake and smoking after transplantation) may be associated with other complications such as de novo tumors and increasing health care costs. Among adult liver transplant patients, the rate of nonadherence to immunosuppressive drugs ranges from 15% to 40%, whereas the rate of nonadherence to clinical appointments ranges from 3% to 47%. The wide range of reported rates is due to different definitions of the term nonadherence and the variety of methods used to measure adherence in the medical literature. Nonadherence seems to be nearly 4 times higher in pediatric and adolescent patients versus adult transplant recipients. Several nonadherence risk factors, such as high medication costs, psychiatric disorders, the conviction that the medication is harmful, and side effects of immunosuppressive therapy, have been described among adult liver transplant patients. The risk factors for nonadherence in pediatric and adolescent liver transplant patients are psychological distress, the functional status of their families, and the impact of immunosuppressive side effects on their physical appearance. A single approach to promoting adherence to general medical prescriptions has been proved to be ineffectual, so a multidisciplinary strategy should be adopted to achieve significant improvements in this field. The aim of this review is to analyze the published literature on adherence in liver transplant patients with a particular focus on the reported prevalence and the identified risk factors. Patients have been split into 2 age groups (adults and children/adolescents) because the scale of the problem and the potential risk factors differ in the 2 groups. Liver Transpl 17:760‐770, 2011.

Nonadherent Behaviors After Solid Organ Transplantation

BACKGROUND AND AIM The effectiveness of any treatment depends not only on the choice of therapy, but also, to a large extent, on the patients active cooperation. Adherence to medical prescriptions and particularly to immunosuppressive therapy is crucial to prevent medical complications that negatively influence graft function and patient survival after organ transplantation. The aim of this study was to assess, among patients who underwent solid organ transplantation, nonadherent behaviors (NAB) to immunosuppressive therapy, to correct lifestyle, and to general medical prescriptions. MATERIALS AND METHODS We evaluated patients who underwent solid organ transplantation from March 2008 to June 2009. All participants completed an anonymous 15-item questionnaire to assess NAB. RESULTS We enrolled 218 organ transplant patients: 103 liver, 50 kidney, 52 heart, and 13 lung. There were 152 men and the overall age was 52.2 ± 0.8 years (mean ± standard deviation [SD]) time from transplantation, 83.6 ± 4.5 months (mean ± SD). Overall 37.9%, 38.8%, and 12.8% of patients reported nonadherence to immunosuppressive therapy, to correct lifestyle, and to general medical prescriptions, respectively. Considering nonadherence to immunosuppressive therapy and to general prescriptions, the percentage of kidney transplant patients who referred NAB was significantly lower compared with other organ transplant patients (P = .008 and P = .04, respectively). Nonadherent patients to immunosuppressive therapy and to general medical prescriptions displayed a longer interval from transplantation compared with adherent patients (P = .02 and P = .03, respectively). Among patients nonadherent to the correct lifestyle, the rates of men and of patients with disability pension were significantly higher compared to adherent patients (P = .001 and P = .002, respectively). CONCLUSIONS Poor adherence to medical prescriptions and to adequate lifestyle is common among organ transplant patients, especially those who have undergone liver transplantation. Psychoeducational interventions for transplanted patients and their families are needed to improve adherence.

Clinical and cognitive correlates of visual hallucinations in dementia with Lewy bodies

Background The presence of recurrent complex visual hallucinations (VHs) is a core feature of dementia with Lewy bodies (DLB). The aim of this study was to investigate which clinical and neuropsychological characteristics are associated with VHs and their predictive value over a 1 year follow-up. Methods 81 DLB patients, 41 with (VH+) and 36 without (VH−) VHs, and 45 patients with Alzheimers disease (AD), were enrolled. All participants underwent extensive neuropsychological testing. Visual–spatial and perceptual abilities were evaluated with the Visual and Object Space Perception (VOSP) battery. Fluctuations in attention, rapid eye movement sleep behaviour disorder (RBD) symptoms, extrapyramidal signs and behavioural disturbances were studied with dedicated clinical scales. Results The presence of VHs was associated with older age and later disease onset, but not with disease duration or with fluctuations, RBD or parkinsonism severity. Cognitive correlates of VHs were deficits in visual attention (digit cancellation: p<0.005) and executive functions (clock drawing: p<0.05; digit span forward: p<0.05) on a background of a slightly worse global cognitive performance (Mini-Mental State Examination: p=0.05). Visual–perceptual and visual–spatial deficits were significantly worse in DLB than in AD patients (VOSP subtests scores 1, 6, 7 and 8) but were not different in DLB VH+ and VH−, except for subtest 6. Poor performance in the visual attention task was an independent predictor of VHs. Discussion Impairment of visual–spatial and perceptual abilities in DLB represents a disease related cognitive signature, independent of the presence of VHs, for which it may represent a predisposing condition. Visual attention, instead, is the main cognitive determinant for the genesis of VHs.

Semantic relevance, domain specificity and the sensory/functional theory of category-specificity.

According to the sensory/functional theory of semantic memory, Living items rely more on Sensory knowledge than Non-living ones. The sensory/functional explanation of category-specificity assumes that semantic features are organised on the basis of their content. We report here a study on DAT patients with impaired performance on Living items and tests of Sensory knowledge, and show that this impairment not only disappears after parcelling out semantic relevance, but is also reversed if this parameter is appropriately manipulated. Although semantic relevance model predicts these results [Sartori, G., & Lombardi, L. (2004). Semantic relevance and semantic disorders. Journal of Cognitive Neuroscience, 16, 439-452], they run counter to both the sensory/functional theory and the domain-specific theory of category-specific impairment.

High specificity of MMSE pentagon scoring for diagnosis of prodromal dementia with Lewy bodies.

BACKGROUND Patients with dementia with Lewy bodies (DLB) may display a different cognitive pattern from Alzheimers disease (AD) with more severe impairment performing visuospatial/visuoconstructive tasks. The aim of this study was to investigate whether the analysis of the MMSE pentagon copy could be a useful diagnostic screening tool in prodromal DLB. METHODS Fifty-three patients with Mild Cognitive Impairment (MCI) were followed over 3-years until a diagnosis of DLB (MCI-DLB: n = 30) and AD (MCI-AD: n = 23) were made according to standard criteria. At the first assessment patients underwent a thorough cognitive assessment including the Qualitative Scoring MMSE Pentagon Test (QSPT), the NPI, the UPDRS as well as questionnaires to determine fluctuations and sleep disorders. RESULTS The percentage of subjects who were unable to determine the correct number of angles in the pentagon copy test was 45.1% of MCI-DLB and 8.3% of MCI-AD patients (sensitivity 41.1%; specificity 91%). Attentive/executive functions and visual-spatial abilities were worse in the MCI-DLB group, while episodic memory impairment was greater in MCI-AD. Subtle extrapyramidal signs (63%) and RBD symptoms (56%) were the most frequent clinical features supporting the diagnosis of MCI-DLB. CONCLUSIONS We suggest that a poor performance in determining the number of angles when performing the pentagon copying test, together with the presence of subtle extrapyramidal signs and symptoms of RBD may serve as a predictive tool for early DLB.

A predominance of category deficits for living things in Alzheimer's disease and Lewy body dementia

Although semantic memory impairment is well documented in patients with dementia of the Alzheimers type, questions remain as to whether the deficit extends to other forms of dementia and whether it differentially affects different domains of knowledge. We examined category naming on two tasks (picture naming and naming-to-description) in patients with Alzheimers disease (AD: n = 11), Lewy body dementia (DLB: n = 11) and healthy elderly matched controls (n = 22). The DLB and AD groups showed significantly worse naming on both tasks, although the AD patients were more impaired than the DLB patients. Like some AD patients, some DLB patients showed evidence of category-specific naming deficits, and strikingly, all 25 significant category dissociations were for living things. The latter finding accords with the preponderance of living deficits previously documented for AD patients, but extends this finding to DLB patients. The implications of this category bias is discussed in relation to relevant models of category specificity.

A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living.

The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities.

Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies

Objective: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimers disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. Methods: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinsons Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagons number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions: Poor performance in the pentagons number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB.

Late-onset OCD as presenting manifestation of semantic dementia

Semantic dementia (SD) is a neurodegenerative disease belonging to the spectrum of frontotemporal dementia that presents with loss of memory for words and prevalent left temporal pole atrophy. Behavioral disorders, particularly obsessive-compulsive symptoms, are frequent during the course of the disease. We describe a patient presenting with late-onset typical obsessive-compulsive disorder (OCD) that lasted for 10 years as an isolated condition before developing clinical and neuroimaging features of SD. This case alerts clinicians that late-onset OCD may be a psychiatric presentation of a neurodegenerative disorder such as frontotemporal dementia and requires an accurate diagnostic work-up.

Combined duloxetine and benzodiazepine-induced visual hallucinations in prodromal dementia with Lewy bodies

OBJECTIVE We describe a patient with prodromal dementia with Lewy bodies (DLB) presenting with drug-induced visual hallucinations (VHs). CASE REPORT A 78-year-old woman complained of daytime recurrent VHs characterized by seeing her face and arms covered in fur and viewing moustaches on her daughters face. VHs started a few days after the beginning of a combination therapy with duloxetine and lorazepam and ceased within 24 h after their discontinuation. Nonamnestic mild cognitive impairment with profound visual perception deficits and very mild extrapyramidal signs, with abnormal brain DaTscan single photon emission tomography, were present. Three years later, cognitive and neurological follow-up assessments supported the diagnosis of DLB. CONCLUSION Perturbation of cerebral serotonergic tone induced by duloxetine, associated with reduced attentional control due to benzodiazepine use, may be the physiopathological substrate of transient VHs in prodromal DLB.