Clinical Perception and Treatment Options for Behavioral and Psychological Symptoms of Dementia (BPSD) in Italy.

Background: Behavioral and psychological symptoms of dementia (BPSD) have a high prevalence, and their presence is associated with a severe impact in terms of social costs. However, dedicated clinical tools or biomarkers to detect these symptoms are lacking. Thus, BPSD management in clinical settings is challenging. The aim of this study was to investigate the perception and the treatment strategies for BPSD in Italian centers working in the dementia field. Methods: A multicenter, national survey was developed by BPSD Study Group of the Italian Neurological Society for Dementia (SINDEM). The survey consisted of a semi-structured questionnaire that was e-mailed to SINDEM members, dementia centers part of the national network of memory clinics (Centers for Cognitive Deterioration and Dementia [CDCD]), and clinicians working in dementia care settings. The questions were focused on (1) perceived global frequency and relevance of BPSD; (2) tools used to assess BPSD; (3) pharmacological treatment for psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disturbances; (4) non-pharmacological treatments; (5) drugs side effects. Results: One-hundred and thirty-six clinicians participated in this study. Seventy-nine participants worked in a CDCD and 57 in other settings. The perceived frequency of BPSD was 74%. BPSD are detected by means of a clinical assessment for 96.3% or a caregiver interview for 97%. For psychosis treatment the first choice was atypical antipsychotics (83.3%), followed by typical antipsychotic (8.9%) and antidepressants (4.8%). For agitation, atypical antipsychotics were the first-choice treatment in 64% of cases and antidepressants in 16.1%. For aggression, the most used drugs were atypical antipsychotics (82.9%). For anxiety, 55.2% use antidepressants, 17.9% use atypical antipsychotics, and 16.9% use benzodiazepines. Interestingly, most of the centers apply non-pharmacological treatments for BPSD. Some differences emerged comparing the responses from CDCD and other care settings. Conclusion: The survey results revealed many differences in BPSD perception, treatment options, and observed side effect according to the clinical setting. This variability can be explained by the absence of clear guidelines, by differences in patients' characteristics, and by clinical practice based on subjective experience. These results suggest that producing guidelines for the pharmacological treatment of BPSD is a major need.

Evaluating Semantic Knowledge Through a Semantic Association Task in Individuals With Dementia.

Conceptual knowledge is supported by multiple semantic systems that are specialized for the analysis of different properties associated with object concepts. Various types of semantic association between concrete concepts-categorical (CA), encyclopedic (EA), functional (FA), and visual-encyclopedic (VEA) associations-were tested through a new picture-to-picture matching task (semantic association task, SAT). Forty individuals with Alzheimer's disease (AD), 13 with behavioral variant of frontotemporal dementia (bv-FTD), 6 with primary progressive aphasia (PPA), and 37 healthy participants were tested with the SAT. Within-group comparisons highlighted a global impairment of all types of semantic association in bv-FTD individuals but a disproportionate impairment of EA and FA, with relative sparing of CA and VEA, in AD individuals. Single-case analyses detected dissociations in all dementia groups. Conceptual knowledge can be selectively impaired in various types of neurodegenerative disease on the basis of the specific cognitive process that is disrupted.

Anxiety and Depression Are Not Related to Increasing Levels of Burden and Stress in Caregivers of Patients With Alzheimer's Disease.

Sixty-nine dyads of patients with Alzheimer's disease and primary caregivers have been followed up for 1 year to evaluate cognitive (Mini-Mental State Examination), functional (Instrumental Activities of Daily Living), and behavioral (Neuropsychiatric Inventory) decline of patient in relation to burden (Caregiver Burden Inventory), stress (Relative Stress Scale), anxiety (State-Trait Anxiety Inventory Y), and depression (Beck Depression Inventory) reported by the caregivers. After 1 year of observation, cognitive and functional scores worsened while behavioral problems remained unchanged and relatively mild in patients. After 1 year, caregivers' scores of scales of anxiety and depression decreased significantly, while stress scores remained unchanged and burden slightly increased. In our opinion, the unexpected improvement in psychological situation of caregivers may be mainly due to educational interventions focused on knowledge of the disease with a particular attention directed toward emotional support and individual needs.

Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene.

Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as scrapie prion protein (PrPSc). These disorders are unique as they occur as sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease, accounting for approximately 85-90% of cases, whereas autosomal dominant genetic forms, due to mutations in the prion protein gene (PRNP), account for 10-15% of cases. Genetic forms show a striking variability in their clinical and neuropathological picture and can sometimes mimic other neurodegenerative diseases.We report a novel PRNP mutation (V189I) in four CJD patients from three unrelated pedigrees. In three patients, the clinical features were typical for CJD and the diagnosis was pathologically confirmed, while the fourth patient presented with a complex phenotype including rapidly progressive dementia, behavioral abnormalities, ataxia and extrapyramidal features, and the diagnosis was probable CJD by current criteria, on the basis of PrPSc detection in CSF by Real Time Quaking-Induced Conversion assay. In all the three patients with autopsy findings, the neuropathological analysis revealed diffuse synaptic type deposition of proteinase K-resistant prion protein (PrPres), and type 1 PrPres was identified in the brain by western blot analysis. So, the histopathological and biochemical profile associated with the V189I mutation was indistinguishable from the MM1/MV1 subtype of sporadic CJD.Our findings support a pathogenic role for the V189I PRNP variant, confirm the heterogeneity of the clinical phenotypes associated to PRNP mutations and highlight the importance of PrPSc detection assays as diagnostic tools to unveil prion diseases presenting with atypical phenotypes.

CHRNA7 Gene and Response to Cholinesterase Inhibitors in an Italian Cohort of Alzheimer's Disease Patients.

Previous studies suggest that genetic variants in CHRNA7, which encodes for the major subunit of the acetylcholine receptor (α7-nAChR), are associated with the clinical response to cholinesterase inhibitors (ChEI) in Alzheimer's disease (AD) patients. We sought to replicate the association of two SNPs in the CHRNA7 gene, rs6494223 and rs8024987, with response to ChEI treatment in an Italian cohort of 169 AD patients, further extending the study to gene-level analysis. None of the tested variants was associated with clinical response. However, rs6494223 showed a consistent effect direction (OR = 1.4; p = 0.17), which after meta-analysis with previous study yielded a significant result (OR = 1.57, p = 0.02, I2 = 0%).

CSF metabolites in the differential diagnosis of Alzheimer's disease from frontal variant of frontotemporal dementia.

The early differentiation between Alzheimer's disease (AD) and frontal variant of frontotemporal dementia (fvFTD) is frequently difficult, albeit critical for the adequate management of patients and their caregivers. In order to assess the accuracy of CSF levels of beta-amyloid 1-42 (Aß), tau (τ) and Thr 181-phosphorilated tau (Pτ) in the early differentiation of AD from fvFTD, we designed a prospective study in which patients have been followed up for at least 2 years. Seventy-two patients with AD and 42 patients with fvFTD showed significantly different CSF levels of Pτ (increased in AD, p = 0.0001), Aß (reduced in AD, p = 0.03), and ratios of Pτ to Aß (p = 0.003). ROC analyses showed that the ratio Pτ/Αß is able to predict diagnosis with an AUC of 0.73 (optimal level being 0.16) corresponding to a sensitivity of 80% and a specificity of 68%. Our findings suggest that CSF metabolites may be the important tools in the early differential diagnosis between AD and fvFTD, albeit to be correlated with clinical, neuropsychological and bio imaging features.

When Rey-Osterrieth's Complex Figure Becomes a Church: Prevalence and Correlates of Graphic Confabulations in Dementia.

Verbal confabulation (VC) has been described in several pathological conditions characterized by amnesia and has been defined as 'statements that involve distortion of memories'. Here we describe another kind of confabulation (graphic confabulation, GC), evident at the recall of the Rey-Osterrieth complex figure (ROCF). In a retrospective study of 267 patients with mild-to-moderate dementia, 14 patients (4.9 %) recalled the abstract ROCF as drawings with recognizable semantic meaning. VC was evident at the story recall test in 19.8% of the study participants. VC and GC were homogeneously distributed among the different types of dementia. VC has been proposed to originate from complex interactions of amnesia, motivational deficit and dysfunction of monitoring systems. On the contrary, GC seems to be the result of a deficit in visual memory replaced by the semantic translation of isolated parts of the ROCF along with a source monitoring deficit.

The frontal assessment battery does not differentiate frontotemporal dementia from Alzheimer's disease.

BACKGROUND: An early differentiation of Alzheimer's disease (AD) from frontotemporal dementia (FTD) is important, since these conditions are essentially different regarding prognosis and therapeutical approach. Until now, no single test is available which allows a reliable differentiation. The Frontal Assessment Battery (FAB) has been found to have good reliability in identifying an executive deficit in frontal syndromes and in extrapyramidal disorders. The ability of the FAB to distinguish AD from FTD in mildly demented patients is less clearly assessed. METHODS: We compared FAB scores in a consecutive series of 33 FTD (frontal variant) and 85 AD patients. RESULTS: FAB global scores in the two groups were very similar, also when considering only mildly demented subgroups [Mini Mental State Examination (MMSE) score > or = 20; 20 FTD and 38 AD patients]. Considering FAB subscores, only the 'go-no go' subtest showed a significant difference, reflecting a poorer inhibitory motor control in AD patients. FAB scores in the two groups of patients correlated with global cognitive decline (MMSE), and with executive and visuospatial test scores, showing good concurrent validity. CONCLUSION: The FAB does not differentiate patients with AD from those with FTD, like all other executive tests. However, it may be useful in the examination of executive function in AD, FTD and several other pathological conditions.

Glucose metabolism and serotonin receptors in the frontotemporal lobe degeneration.

In patients with the frontal variant of frontotemporal lobar degeneration (fv-FTLD), behavioral abnormalities may vary from apathy with motor slowness (apathetic form) to disinhibition with agitation (disinhibited form). These clinical presentations may be related to specific regional cerebral dysfunction and to deficit in the serotoninergic system. We studied cerebral glucose uptake using (18)F-fluorodeoxyglucose and positron emission tomography in 18 patients fulfilling clinical criteria for fv-FTLD and showing, respectively, an apathetic or disinhibited behavioral syndrome. In eight of these patients, we also evaluated the 5-hydroxytryptamine-2A receptor cerebral receptor distribution with [(11)C]MDL and positron emission tomography. We found a reduction of frontal glucose metabolism in the whole group of fv-FTLD patients. Apathetic syndrome was associated with a prevalent dorsolateral and frontal medial hypometabolism, whereas the disinhibited syndrome demonstrated a selective hypometabolism in interconnected limbic structures (the cingulate cortex, hippocampus/amygdala, and accumbens nucleus). The in vivo measurements of [(11)C]MDL indicated a significant reduction of 5-hydroxytryptamine-2A receptors in orbitofrontal, frontal medial, and cingulate cortices. These (18)F-fluorodeoxyglucose positron emission tomography changes can be considered as specific functional markers of the different behavioral presentations in fv-FTLD. The serotoninergic system dysfunction provides a rationale for therapeutic trials with selective serotonin reuptake inhibitors.