CD33 and SIGLECL1 Immunoglobulin Superfamily Involved in Dementia.

Sialic acid-binding immunoglobulin-type lectins, which are predominantly expressed in immune cells, represent a family of immunomodulatory receptors with inhibitory and activating signals, in both healthy and disease states. Genetic factors are important in all forms of dementia, especially in early onset dementia. CD33 was recently recognized as a genetic risk factor for Alzheimer disease (AD). Here, we present a 2-generation family with 4 members, the father and the 3 siblings, characterized by an early form of unusual dementia exhibiting a behavioral variant close to behavioral variant frontotemporal dementia phenotype and severe forms of memory loss suggestive of AD. We analyzed the CD33 gene in this family and identified 10 single nucleotide polymorphisms (SNPs) in a linkage disequilibrium block associated with the disease. We also identified a tag SNP, rs2455069-A>G, in CD33 exon 2 that could be involved with dementia risk. Additionally, we excluded the presence of C9orf72 expansion mutations and other mutations previously associated with sporadic FTD and AD. The tag SNP association was also analyzed in selected sporadic AD patients from the same Southern Italy region. We demonstrate that CD33 and SIGLECL1 have a significantly increased level of expression in these patients.

Mini-Mental State Examination: new normative values on subjects in Southern Italy.

OBJECTIVE: The aims of the present study were: (a) to obtain new normative data of the Italian version of the Mini-Mental Examination State (MMSE) (Measso et al. in Dev Neuropsychol 9:77-85, 1993) by administering the tool to a sample of normal Italian individuals more representative of the current Italian population; (b) to compare the sensitivity of this tool in detecting patients suffering from Alzheimer's disease (AD according to NIA-AA), as compared to the those reported in previous normative Italian studies. METHODS: MMSE was administered to 314 normal subjects recruited among individuals (and/or their relatives) attending the Offices of General Practitioners (GP) or Memory Clinics in Campania (Italy) by convenience sampling. A group of 47 patients with AD were included into the study. The effect of demographic variables on the raw MMSE scores of normal subjects was checked by multiple linear regression assuming MMSE scores as dependent variable and age, gender and education as the independent one(s). Therefore, a simultaneous regression model was constructed to correct the raw scores according the sensitive variables. Correction grid and equivalent scores were devised to classify subject's performance. RESULTS: The mean raw MMSE score was 27.78 (SD = 1.80) (range 22-30/30). There was no significant difference between scores achieved by men or women (p = 0.688). Multiple linear regression analysis showed a significant effect of age and years of school attendance on the MMSE raw score, whereas gender did not show any significant effect. The cutoff score, distinguishing between pathological and normal performances, was fixed at the fifth centile corresponding to 24.9/30, higher than the current score of 23.8/30. The new cutoff value was able to identify 44/47 patients with AD, in contrast to 38/47 subjects detected by currently used norms. CONCLUSIONS: (1) A more updated and representative population sample; (2) a new cutoff threshold able to distinguish between normal and pathological performances; (3) a correction grid that reduces the risk of false-positive and false-negative values due to the influence of the main demographic factors; (4) greater sensitivity, compared to previous Italian normative studies in identifying people with dementia.

The closing-in phenomenon in constructional tasks in dementia and mild cognitive impairment.

OBJECTIVE: Closing-in (CI) consists in copying drawings near to (near-CI) or superimposed on (adherent-CI) the model and often occurs in dementia and mild cognitive impairment (MCI). We assessed whether a visuo-constructional task not requiring a grapho-motor response is sensitive to identify CI in Alzheimer's disease (AD), fronto-temporal dementia (FTD), vascular dementia (VD), and MCI. METHOD: We enrolled a sample of 162 patients with dementia (AD, FTD, or VD), 66 individuals with MCI, and 20 healthy adults (HAs) who completed a neuropsychological assessment and the Stick Design test that requires arranging matches for reproducing geometrical figures. RESULTS: CI in the Stick test was slightly (but not significantly) more frequent than that observed in the copying drawing task. CI frequency on both tests was high and similar in AD and FTD and lower in VD and MCI. On both tests, near-CI was the most common error in VD and MCI, whereas adherent-CI prevailed in patients with AD; a similar percentage of near-CI and adherent-CI was observed in FTD. Last, in the participants with dementia and MCI, the number of CIs was significantly correlated with an index of control and executive functions but not with spatial short-term memory. CONCLUSIONS: CI occurs with the same frequency in AD, VD, and FTD, but the prevalent type of CI varies across syndromes. The Stick Design test is a useful task to assess CI and its specific forms in dementia and MCI. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Paradigm shift for the treatment of hereditary haemophilia: Towards precision medicine.

Patients with haemophilia A (HA) or B (HB) experience spontaneous limb- or life-threatening bleedings which are prevented by regular prophylactic intravenous infusions of the deficient coagulation factor (FVIII or FIX). Prophylaxis with subcutaneous long-acting non-factor products that improve in vivo thrombin generation is now under intensive investigation (concizumab, fitusiran) or successfully employed (emicizumab) in haemophilia patients. Both haemophilia patients with/without inhibitors take advantage of non-factor products employed alone. In those who also need bypassing agents (or FVIII concentrates) for breakthrough bleeds, thromboembolic events and/or thrombotic microangiopathy may occur. By enhancing thrombin generation, prothrombotic mutations co-segregating with FVIII/FIX gene mutations may trigger thrombotic episodes in HA patients carrying acquired thrombogenic factors (e.g. venous catheters). A thorough knowledge of individual needs increasingly contributed to improve comprehensive care and personalize treatments in haemophilia. Integrating genomics, lifestyle and environmental data is expected to be key to: 1) identify which haemophilia patients are less likely to benefit from a given intervention; 2) define optimal dosing and scheduling of bypassing agents (or FVIII) to employ in combination with non-factor products; 3) establish tests to monitor in vivo thrombin generation; 4) improve communication and deliver results to individuals. As individual outcomes will be improved and the risk of adverse events minimized, non-factor products will come into wider use within the haemophilia community, and patients will hopefully have no more risks of breakthrough bleeds. The risks of a normal life for a "former haemophilia patient" is likely to change the treatment landscape and the structure of haemophilia Centers.

Enactment effect in patients with Alzheimer's disease.

Introduction: Subjects can improve their performance on memory for action phrases if, during the encoding condition, they self-perform actions associated with verbs (subject-performed condition), or if they perceive the actions carried out by experimenter (experimenter-performed condition), with respect to a verbal task condition in which they only read or listen to the stimuli. This facilitation is labeled "Enactment effect" (EE), and is thought to be associated with episodic integration processes binding actions and nouns together in a coherent representation. Only recently, studies addressed EE in AD individuals reporting significant improvements on memory tasks in the subject-performed encoding condition. However, no studies tried to explore the cognitive mechanisms supporting EE in AD individuals. Method: Performance on recognition and cued recall tasks for action phrases were assessed in a sample of 32 mild-to-moderate AD individuals and 30 healthy adults, in verbal, subject-performed and experimenter-performed encoding conditions. Moreover, a cognitive assessment was completed to explore the possible correlates of EE in our participants. Results: Results showed that both subject-performed and experimenter-performed encoding conditions produced similar advantages over the verbal condition, in both memory tasks in both groups. Moreover, these memory advantages were strongly associated to executive processes, in both AD and healthy adults. Conclusions: The present study confirmed that EE is spared in mild to moderate AD. Our findings supported the role of episodic integration processes and suggested a contribution of executive processes in EE.

The Italian version of the quick mild cognitive impairment (Qmci-I) screen: normative study on 307 healthy subjects.

OBJECTIVE: To devise an Italian version of the quick mild cognitive impairment screen (Qmci) and to obtain normative data. METHODS: An Italian version of the Qmci screen (Qmci-I) was administered to 307 subjects free from cognitive impairment. The normative sample was divided into three age levels (50-59; 60-69 and 70-80 years) and four education levels (3-5; 6-8; 9-13; >13 years of school attendance). Multiple regression analyses were used to evaluate the effect of age, sex and schooling on Qmci-I scores (overall and by domains) and to calculate cut-off values, with reference to the confidence interval on the fifth centile. RESULTS: The mean Qmci-I score was 64/100 (SD = 11). The age variable showed a significant negative effect on the overall Qmci-I score, with older people performing worse than younger ones. Conversely, education was associated with higher scores. Significant effects of age and education affected logical memory alone. For the other domains, the following effects were found: (1) higher age associated with lower scores on delayed recall; (2) higher education levels associated with higher scores on immediate recall, clock drawing and word fluency. The adjusted cut-off score for the Qmci-I screen in this sample was 49.4. Qmci-I scores were weakly correlated with those of MMSE (rho = 0.20). CONCLUSIONS: The Qmci-I is a rapid and multi-domain short cognitive screening instrument useful for evaluating cognitive functions. However, like other screening tools, it is significantly influenced by age and education, requiring normative data and correction of values when used in the clinical practice.

Simultaneous resting-state FDG-PET/fMRI in Alzheimer Disease: Relationship between glucose metabolism and intrinsic activity.

Simultaneously evaluating resting-state brain glucose metabolism and intrinsic functional activity has potential to impact the clinical neurosciences of Alzheimer Disease (AD). Indeed, integrating such combined information obtained in the same physiological setting may clarify how impairments in neuroenergetic and neuronal function interact and contribute to the mechanisms underlying AD. The present study used this multimodality approach to investigate, by means of a hybrid PET/MR scanner, the coupling between glucose consumption and intrinsic functional activity in 23 patients with AD-related cognitive impairment ranging from amnestic mild cognitive impairment (MCI) to mild-moderate AD (aMCI/AD), in comparison with a group of 23 healthy elderly controls. Between-group (Controls > Patients) comparisons were conducted on data from both imaging modalities using voxelwise 2-sample t-tests, corrected for partial-volume effects, head motion, age, gender and multiple tests. FDG-PET/fMRI relationships were assessed within and across subjects using Spearman partial correlations for three different resting-state fMRI (rs-fMRI) metrics sensitive to AD: fractional amplitude of low frequency fluctuations (fALFF), regional homogeneity (ReHo) and group independent component analysis with dual regression (gICA-DR). FDG and rs-fMRI metrics distinguished aMCI/AD from controls according to spatial patterns analogous to those found in stand-alone studies. Within-subject correlations were comparable across the three rs-fMRI metrics. Correlations were overall high in healthy controls (ρ = 0.80 ±â€¯0.04), but showed a significant 17% reduction (p < 0.05) in aMCI/AD patients (ρ = 0.67 ±â€¯0.05). Positive across-subject correlations were overall moderate (ρ = 0.33 ±â€¯0.07) and consistent across rs-fMRI metrics. These were confined around AD-target posterior regions for metrics of functional connectivity (ReHo and gICA-DR). In contrast, FDG/fALFF correlations were distributed in the frontal gyrus, thalami and caudate nuclei. Taken together, these results support the presence of bioenergetic coupling between glucose utilization and rapid transmission of neural information in healthy ageing, which is substantially reduced in aMCI/AD, suggesting that abnormal glucose utilization is in some way linked to communication breakdown among brain regions impacted by the underlying pathological process.

The Closing-In Phenomenon in an Ecological Walking Task.

OBJECTIVES: Alzheimer's disease (AD) patients may show the Closing-in (CI), a tendency to reproduce figures close to or superimposed on the model. AD patients with CI might manifest reduced functional independence compared to AD patients without CI, but no study directly assessed if CI can hamper common daily living activities. To address this issue here we investigated whether AD patients with CI veer their walking trajectory toward irrelevant objects more often than AD patients without CI. METHODS: Fifty AD individuals, and 20 age- and education-matched healthy adults, underwent a graphic copying task to detect CI and a newly developed walking task to assess the tendency to veer toward irrelevant objects and to bump into them. All participants also completed a comprehensive neuropsychological battery to assess dementia severity; impairments in frontal/executive, visuo-spatial, visuo-constructional, and memory domains; and functional independence in daily living activities. RESULTS: Graphic CI occurred in 34/50 (68%) AD patients (AD-CI group) who achieved significantly lower scores on frontal/executive abilities, and daily living functioning than AD individuals not showing CI. Most AD-CI patients (20/34; 58.8%) also showed at least one veering error in the walking task. Participants with CI and veering errors showed significantly poorer performance on Stroop test, and lower level of functional independence than AD individuals with CI in isolation. CONCLUSIONS: CI on graphic tasks can identify difficulties in walking and in complying with everyday activities in AD patients. These observations demonstrate the value of assessing CI in copying tasks. (JINS, 2018, 24, 437-444).

GRN deletion in familial frontotemporal dementia showing association with clinical variability in 3 familial cases.

Progranulin (GRN) gene mutations have been genetically associated with frontotemporal dementia (FTD) and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of 3 pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritance patterns. We present evidence that all the available patients in these 3 familial cases are carrying the rare GRN gene exon 6 deletion g10325_10331delCTGCTGT (relative to nt 1 inNG_007886.1), alias Cys157LysfsX97. This mutation was previously described in 2 sporadic cases but was never associated with familial cases. Our patients demonstrate heterogeneous clinical phenotypes, such as the behavioral variant (bvFTD) in the affected men and the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) in the affected woman. Haploinsufficiency was revealed by both quantitative real-time PCR of the gene and protein analyses. These findings provide further support for a previously proposed role for the GRN gene in the genetic etiology of FTD and its phenotypic variability.

Spatio-temporal and kinematic gait analysis in patients with Frontotemporal dementia and Alzheimer's disease through 3D motion capture.

Alzheimer's disease (AD) and behavioral variant of Frontotemporal Dementia (bvFTD) are characterized respectively by atrophy in the medial temporal lobe with memory loss and prefrontal and anterior temporal degeneration with dysexecutive syndrome. In this study, we hypothesized that specific gait patterns are induced by either frontal or temporal degeneration. To test this hypothesis, we studied the gait pattern in bvFTD (23) and AD (22) patients in single and dual task ("motor" and "cognitive") conditions. To detect subtle alterations, we performed motion analysis estimating both spatio-temporal parameters and joint excursions. In the single task condition, the bvFTD group was more unstable and slower compared to healthy subjects, while only two stability parameters were compromised in the AD group. During the motor dual task, both velocity and stability parameters worsened further in the bvFTD group. In the same experimental conditions, AD patients showed a significantly lower speed and stride length than healthy subjects. During the cognitive dual task, a further impairment of velocity and stability parameters was observed in the bvFTD group. Interestingly, during the cognitive dual task, the gait performance of the AD group markedly deteriorated, as documented by the impairment of more indices of velocity and stability. Finally, the kinematic data of thigh, knee, and ankle were more helpful in revealing gait impairment than the spatio-temporal parameters alone. In conclusion, our data showed that the dysexecutive syndrome induces specific gait alterations. Furthermore, our results suggest that the gait worsens in the AD patients when the cognitive resources are stressed.

Evaluation of the efficacy of animal-assisted therapy based on the reality orientation therapy protocol in Alzheimer's disease patients: a pilot study.

BACKGROUND: The aim of this study was to evaluate the efficacy of animal-assisted therapy (AAT) in elderly patients affected by Alzheimer's disease based on the formal reality orientation therapy (ROT) protocol. METHODS: Our study was carried out at an Alzheimer's centre for 6 months. A homogeneous sample (age, Mini-Mental State Examination (MMSE), 15-item Geriatric Depression Scale (GDS)) of 50 patients was selected at random and successively. Patients were divided into three groups: (i) 20 patients received a course of AAT (AAT group) based on the ROT protocol; (ii) 20 patients were engaged exclusively in activities based on the ROT group; and (iii) 10 patients (control group) participated in no stimulations. MMSE and GDS were administered at time 0 (T0 ) and time 1 (T1 ) to all three groups. Differences within groups between T0 and T1 for GDS and MMSE scores were analyzed by Student's t-test. Differences between group means were analyzed using an anova test with the Bonferroni-Dunn test for post-hoc comparisons. RESULTS: Both the AAT group and ROT group had improved GDS scores and showed a slight improvement in terms of mood. On the GDS, the AAT group improved from 11.5 (T0 ) to 9.5 (T1 ), and the ROT group improved from 11.6 (T0 ) to 10.5 (T1 ). At the same time, a slight improvement in cognitive function, as measured by the MMSE, was observed. In the AAT group, mean MMSE was 20.2 at T0 and 21.5 at T1 , and in the ROT group, it was 19.9 at T0 and 20.0 at T1 . In the control group, the average values of both the GDS and MMSE remained unchanged. The Bonferroni-Dunn results showed statistically significant differences between groups, particularly between the AAT group and the other two (P < 0.001). CONCLUSIONS: Pet therapy interventions based on the formal ROT protocol were effective and, compared to the ROT, provided encouraging and statistically significant results.

A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia.

Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10(-7) and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis.

Relationships between Environmental Dependency and Closing-in in Patients with Fronto-temporal Dementia.

Environmental dependency (ED) phenomena, including utilization behavior and imitation behavior, are clinical manifestations typically observed in patients with the behavioral variant of fronto-temporal dementia (bvFTD), who may also show the closing-in (CI) phenomenon. Here, we explored the neuropsychological correlates of ED and CI in bvFTD, and the association of ED with CI to clarify the mechanisms underlying these clinical manifestations. Thirty-one bvFTD patients underwent a wide cognitive assessment in addition to special tasks to detect occurrence of CI and ED phenomena. Both ED and CI phenomena were present in more than half of the sample. Logistic regression analyses revealed that both ED and CI phenomena were significantly associated with poor scores on frontal neuropsychological tests. Although ED and CI often co-occurred, 3/12 patients with CI did not show ED, and 5/18 patients with ED did not show CI. A logistic regression model showed that the presence of ED was not significantly associated to CI. CI and ED are associated to progressive derangement of frontal functions in bvFTD. However, specific frontal dysfunctions might explain the occurrence of either phenomenon in isolation.

Dysexecutive performance of healthy oldest old subjects on the Frontal Assessment Battery.

BACKGROUND AND AIMS: Frontal lobes and executive functions appear to be more vulnerable to normal aging than other cerebral regions and domains. The aim of the study was to evaluate executive functions by the Frontal Assessment Battery (FAB) in healthy oldest old subjects free of dementia. METHODS: Thirty-two healthy oldest old subjects (age range 85-97 yrs) and 32 young old subjects (aged 61-74 yrs) were studied. All subjects were living with their families or alone and were considered normal, since they were fully independent in their activities of daily living and without signs or symptoms characteristic of any type of dementia. Mental status was assessed by the Mini- Mental State Examination (MMSE) and executive functions by the FAB. RESULTS: Mean MMSE scores were 23.12 ± 4.68 in oldest old and 26.78 ± 2.60 in young old subjects (p<0.005). Delayed recall was the most impaired domain, followed by executive (Serial 7). Mean FAB scores were 9.37 ± 4.14 in the oldest old and 13.53 ± 2.12 in the young old (p<0.0001). Among the FAB subtests, conceptualization was the most impaired in both groups, with sensitivity to interference and inhibitory control exhibiting higher discrimination between the oldest old and young old. Education influenced performance on MMSE and FAB in both groups. CONCLUSIONS: On the FAB test, healthy oldest old subjects showed executive impairment with respect to the young olds, due to the involvement of functions depending on activities of different regions of the frontal lobes. FAB results were consistent with the hypothesis that frontal lobes have a high vulnerability to normal aging. Short composite batteries like the FAB are suitable for rapid and reliable description of patterns of executive functioning in the oldest old.

SPECT imaging of GABA(A)/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment.

PURPOSE: The involvement of neocortical and limbic GABA(A)/benzodiazepine (BZD) receptors in Alzheimer's disease (AD) is controversial and mainly reported in advanced stages. The status of these receptors in the very early stages of AD is unclear and has not been explored in vivo. Our aims were to investigate in vivo the integrity of cerebral cortical GABA(A)/BZD receptors in subjects with amnestic mild cognitive impairment (MCI) and to compare possible receptor changes to those in cerebral perfusion. METHODS: [(123)I]Iomazenil and [(99m)Tc]HMPAO SPECT images were acquired in 16 patients with amnestic MCI and in 14 normal elderly control subjects (only [(123)I]iomazenil imaging in 5, only [(99m)Tc]HMPAO imaging in 4, and both [(123)I]iomazenil and [(99m)Tc]HMPAO imaging in 5). Region of interest (ROI) analysis and voxel-based analysis were performed with cerebellar normalization. RESULTS: Neither ROI analysis nor voxel-based analysis showed significant [(123)I]iomazenil binding changes in MCI patients compared to control subjects, either as a whole group or when considering only those patients with MCI that converted to AD within 2 years of clinical follow-up. In contrast, the ROI analysis revealed significant hypoperfusion of the precuneus and posterior cingulate cortex in the whole group of MCI patients and in MCI converters as compared to control subjects. Voxel-based analysis showed similar results. CONCLUSION: These results indicate that in the very early stages of AD, neocortical and limbic neurons/synapses expressing GABA(A)/BZD receptors are essentially preserved. They suggest that in MCI patients functional changes precede neuronal/synaptic loss in neocortical posterior regions and that [(99m)Tc]HMPAO rCBF imaging is more sensitive than [(123)I]iomazenil GABA(A)/BZD receptor imaging in detecting prodromal AD.

Blood ammonia levels in liver cirrhosis: a clue for the presence of portosystemic collateral veins.

BACKGROUND: Portal hypertension leads to the formation of portosystemic collateral veins in liver cirrhosis. The resulting shunting is responsible for the development of portosystemic encephalopathy. Although ammonia plays a certain role in determining portosystemic encephalopathy, the venous ammonia level has not been found to correlate with the presence or severity of this entity. So, it has become partially obsolete. Realizing the need for non-invasive markers mirroring the presence of esophageal varices in order to reduce the number of endoscopy screening, we came back to determine whether there was a correlation between blood ammonia concentrations and the detection of portosystemic collateral veins, also evaluating splenomegaly, hypersplenism (thrombocytopenia) and the severity of liver cirrhosis. METHODS: One hundred and fifty three consecutive patients with hepatic cirrhosis of various etiologies were recruited to participate in endoscopic and ultrasonography screening for the presence of portosystemic collaterals mostly esophageal varices, but also portal hypertensive gastropathy and large spontaneous shunts. RESULTS: Based on Child-Pugh classification, the median level of blood ammonia was 45 mcM/L in 64 patients belonging to class A, 66 mcM/L in 66 patients of class B and 108 mcM/L in 23 patients of class C respectively (p < 0.001).The grade of esophageal varices was concordant with venous ammonia levels (rho 0.43, p < 0.001). The best area under the curve was given by ammonia concentrations, i, e., 0.78, when comparing areas of ammonia levels, platelet count and spleen longitudinal diameter at ultrasonography. Ammonia levels predicted hepatic decompensation and ascites presence (Odds Ratio 1.018, p < 0.001). CONCLUSION: Identifying cirrhotic patients with high blood ammonia concentrations could be clinically useful, as high levels would lead to suspicion of being in presence of collaterals, in clinical practice of esophageal varices, and pinpoint those patients requiring closer follow-up and endoscopic screening.

Fronto-temporal dementia presenting as Geschwind's syndrome.

Geschwind described a syndrome (Geschwind syndrome, GS) in patients with temporal lobe epilepsy, characterized by sexual behavioural disorders, hyper-religiosity, hypergraphia and viscosity. In this report we describe a patient affected by fronto-temporal dementia (FTD), who showed all the personality changes of GS without having epilepsy, and suggest that clinicians should be aware of several other features in FTD, such as hyposexuality and hypergraphia, which are usually not noted during the diagnostic evaluation.

Role of functional performance in diagnosis of dementia in elderly people with low educational level living in Southern Italy.

BACKGROUND AND AIMS: Diagnosis of dementia is often difficult in subjects with low educational level. Our aim was to evaluate the role of functional performance and the possibility of preferring scores of activities of daily living (ADL) and instrumental activities of daily living (IADL) in screening elderly people for diagnosis of dementia in a rural population of Southern Italy with a very high percentage of non-educated subjects. METHODS: a random sample of 300 residents, out of 1089 subjects over 60 years of age living in San Marcellino (Caserta, Campania), received door-to-door visit for information about their medical history, with clinical evaluation of general geriatric conditions, including the cumulative illness rating scale (CIRS). Dementia was diagnosed if subjects had a Clinical Dementia Rating score (CDR) > or = 1 and according to the criteria of DSMIV, but not according to scores on the Mini Mental State Examination (MMSE), ADL and IADL. Two hundred and nineteen normal subjects (NS) and 75 patients with dementia (DP) were evaluated. RESULTS: in NS, their mean age- and education-corrected MMSE score was 22.15 (lower than the normal cut-off value of 23.8) and 12.60 in DP (p<0.0001). In NS, the mean ADL score was higher than in DP (5.53 vs 2.64, p<0.0001); only age was correlated with ADL scores (coeff=-0.44, t=-4.557, p<0.0001). Assuming age as covariate, ADL scores highly differentiated DP from NS (F(1, 289)=26.083, p<0.0001). In both sexes, mean IADL scores were higher in NS than in DP (4.46 vs 1.80 in men, p<0.0001; 6.85 vs 2.31 in women, p<0.0001). Age and education did not influence IADL scores in men, but age greatly affected performance in women. IADL scores clearly differentiated NS from DP. In NS, a positive correlation was evident between ADL and IADL scores (r=0.234, p<0.0005), but neither scores correlated with the MMSE scores, even when correlation was performed separately for men and women. In DP, a strong correlation was observed between ADL and IADL scores (r=0.709, p<0.0001) and significant correlations were also evident between the scores of MMSE and both ADL (r=0.492,p<0.0001) and IADL (r=0.398, p<0.0004). CONCLUSIONS: in a rural community with a high prevalence of non-educated subjects, cognitive impairment is related to education, whereas independent functioning is limited mainly to age and not to cognition, if the latter remains (relatively) unimpaired. These results point to the importance of an "ecological" approach to the evaluation of elderly people, particularly those living in small rural communities, where education and the social environment may give rise to difficulties in diagnosis of dementia. The assessment of functional autonomy by ADL and IADL scales may be a better screening tool in diagnosing dementia than the MMSE scores.

Mental status impairment in patients with West Haven grade zero hepatic encephalopathy: the role of HCV infection.

BACKGROUND: In patients with cirrhosis, subclinical hepatic encephalopathy, which negatively affects the activity of daily living, is often unidentified. In a multicenter observational study, we investigated the possibility of detecting minimal neurological changes consistent with subclinical hepatic encephalopathy by using the Trail Making Test in a cohort of patients with liver cirrhosis at hospital admission. METHODS: Seventy-seven consecutive patients with liver cirrhosis were studied (mean age, 69.5 +/- 9.1; 95% confidence interval, 67.5-71.6 years). In all patients, possible encephalopathy was investigated according to the West Haven criteria. All those free of any sign of encephalopathy (West Haven 0) were also studied by the Trail Making Test forms A and B. The Child-Pugh score was determined in all patients, and results were compared with the West Haven stage. Exclusion criteria were use of benzodiazepine, beta adrenergic blockers, alcohol, or antiepileptic drugs, or coexistence of depression, dementia, Parkinson's disease, or chronic or acute cerebral vasculopathy. RESULTS: Of the 77 patients, 44 (57.1%, 23 men and 21 women) had West Haven score 0, but among these, 26 (59.1%) were diagnosed with mental impairment likely linked to minimal hepatic encephalopathy. Severity of liver disease correlated with the presence of likely minimal hepatic encephalopathy, because the prevalence of abnormal Trail Making Test results increased from 22.2% in Child-Pugh A, to 63.4% and 74.0% in Child-Pugh B and C, respectively. CONCLUSIONS: The investigation of patients with cirrhosis by the West Haven test is not sufficient to identify subclinical forms of encephalopathy. The Trail Making Test (a simple, inexpensive test) in our series evidenced poor psychometric performance in more than half of the patients who were free of manifest encephalopathy. Subclinical hepatic encephalopathy was present mostly in patients with HCV-related cirrhosis. Detecting minimal hepatic encephalopathy in patients with cirrhosis may help improve their quality of life.