Empowering general practitioners in dementia care: The ANTISTIGMA education intervention in Europe.

BACKGROUND: There is a well-documented lack or delay of diagnosis of dementia in all countries, including in Europe. Most general practitioners (GPs) have acquired adequate academic and scientific information about dementia but avoid using it in practice because of stigma. OBJECTIVES: To persuade GPs of their role in dementia detection, an Antistigma education intervention was designed, with teaching objectives focusing on "Why" and "How" to diagnosis and manage dementia, based on ethical and practical content, as opposed to classical training centered on teaching "What", with mainly academic content. METHODS: During the European Joint Action "ACT ON DEMENTIA", the Antistigma education intervention was implemented in four Universities: Lyon and Limoges (France), Sofia (Bulgaria) and Lublin (Poland). General data, including information about training and experience in dementia, was collected. Specific scales measured Dementia Negative Stereotypes DNS and Dementia Clinical Confidence D-CO before and after training. RESULTS: 134 GPs and 58 residents R completed the training. The participants were mainly women (74%), and the mean age was 42.8 ± 13.2. Before training, participants expressed difficulties in defining GPs role and worries about inflicting Stigma, Risks of diagnosis, Lack of benefit and Communication difficulties. Participants' D-CO was significantly higher for Diagnosis process (64%) than for other clinical situations. After training, total NS was reduced from 34.2% to 29.9% (p < 0.001), and stereotypes were improved: GPs' role (40.1% reduced to 35.9%; p < 0.001), Stigma (38.7% reduced to 35.5%; p < 0.001), Risks of diagnosis (39.0% reduced to 33.3%; p < 0.001), Lack of Benefit (29.3% reduced to 24.6%; p < 0.001) and Communication difficulties (19.9% reduced to 16.9%; p < 0.001). After training, D-CO was significantly increased in all the clinical situations (p < 0.001), but stayed highest for Diagnosis Process. There was no significant difference between the universities. Participants who benefited best from the Antistigma education intervention were those without training in Geriatrics and those working in nursing homes (who reduced the most D-NS), as well younger participants and those who managed less than five people living with dementia per week (who increased the most D-CO). CONCLUSION: The Antistigma program is based on the idea that most often GPs and R have acquired adequate academic and scientific information about dementia but avoid using it in practice because of stigma. These results outline the importance of addressing ethical issues and practical management situations in dementia education, to empower GPs in dementia care.

Phenotypic variability and neuropsychological findings associated with C9orf72 repeat expansions in a Bulgarian dementia cohort.

BACKGROUND: The GGGGCC repeat expansion in the C9orf72 gene was recently identified as a major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in several European populations. The objective of this study was to determine the frequency of C9orf72 repeat expansions in a Bulgarian dementia cohort and to delineate the associated clinical features. METHODS AND FINDINGS: PCR-based assessments of the C9orf72 hexanucleotide repeat expansion in all study samples (including 82 FTD, 37 Alzheimer's disease (AD), and 16 other neurodegenerative/dementia disorder cases) were performed. We report the clinical, neuropsychological, and neuroimaging findings obtained for the C9orf72 repeat expansion carriers. Of the 135 cases screened, 3/82 (3.7%) of all FTD cases and 1/37 (2.7%) of all clinical AD cases had a C9orf72 repeat expansion. In this cohort, the C9orf72 pathological expansion was found in clinical diagnoses bridging the FTD, parkinsonism, ALS and AD spectrum. Interestingly, we showed early writing errors without aphasia in two subjects with C9orf72 expansions. CONCLUSIONS: This study represents the first genetic screening for C9orf72 repeat expansions in a Bulgarian dementia cohort. The C9orf72 repeat expansion does not appear to be a common cause of FTD and related disorders. This report confirms the notion that C9orf72 repeat expansions underlie a broad spectrum of neurodegenerative phenotypes. Relatively isolated agraphia in two cases with C9orf72 repeat expansions is a strong motivation to provide detailed and sophisticated oral and written language assessments that can be used to more precisely characterize early cognitive deficits in these heterogeneous conditions.

Investigation of neuropsychological characteristics of very mild and mild dementia with Lewy bodies.

INTRODUCTION: The study aimed to compare the profile of very mild and mild dementia with Lewy bodies (DLB) patients with disease duration up to 5 years in order to find markers for faster progression in this early stage. METHOD: We investigated 45 DLB patients with disease duration up to 5 years and 22 normal controls. DLB patients were divided into two subgroups on the basis of the Mini-Mental State Examination (MMSE): very mild and mild. RESULTS: Compared to normal controls, very mild DLB patients show significant deficits on tests for attention/executive functions, language, visuospatial/constructional abilities, and retrieval of the episodic memory. In addition, mild DLB (mDLB) patients show a significantly lower score on recall and recognition of the Free and Cued Selective Reminding Test (FCSRT), Trail Making Test Part B (TMT-B), Stroop test, verbal fluency, and Clock Drawing Test than did very mild DLB (vmDLB) patients. Patients with mDLB also have more visual hallucinations, but not significant motor differences compared to vmDLB. CONCLUSIONS: In the present work we found that faster progression to the mild DLB stage in the first few years of the disease is mainly related to deterioration of memory, attention/executive functions, and visuospatial abilities, as well as an increased frequency of visual hallucinations.

Neuropsychological and neuroimaging markers in prediction of cognitive impairment after ischemic stroke: a prospective follow-up study.

BACKGROUND: There are few longitudinal studies with controversial results examining delayed changes in cognition after ischemic stroke and predictive values of neuropsychological and neuroimaging markers. OBJECTIVE: The objectives of this study were to evaluate the delayed changes in cognition in poststroke patients and their relationship to the neuropsychological and neuroimaging markers measured during the acute poststroke phase. METHODS: Eighty-five first-ever stroke inpatients (mean age 65.6±5.6 years) without previous cognitive complaints were prospectively evaluated with a comprehensive neuropsychological battery at the 5th day and the 1st, 6th, and 12th months. A wide range of clinical, radiological, and neuropsychological variables were examined. RESULTS: Our results showed significantly poorer performance on mini-mental state examination, memory, attention/executive functions, and processing speed in patients with stroke in comparison with stroke-free cognitively intact controls. Multiple regression analysis revealed that hippocampal atrophy is the strongest predictor of delayed cognitive impairment. Secondary divided subgroups according to Isaacs Set Test (IST) score showed that patients with IST score ≤28 had different patterns of cognitive and neurological impairment after 1 year. Baseline impairments in attention/executive functions and memory were associated with development of dementia in poststroke patients. CONCLUSION: Executive functioning deficit appears to have a predictive power for cognitive impairment progression. The study suggests that IST as a screening test has a potential to be a reliable and quick tool for poststroke cognitive impairment evaluation and delayed cognitive and neurological outcome. Hippocampal atrophy was the strongest predictor for cognitive impairment outcome, even in poststroke cognitive impairment. The findings may set the stage for better poststroke management.

Clinical and Neuropsychological Differences between Mild Parkinson's Disease Dementia and Dementia with Lewy Bodies.

BACKGROUND: The specific profile of dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) in the earliest stages of dementia is still unclear and subject of considerable controversy. METHODS: We investigated 27 PDD patients and 24 DLB patients with parkinsonism in the early stage of dementia, i.e. with a Mini-Mental State Examination score of ≥24. RESULTS: Compared to PDD, patients with DLB demonstrated significantly lower scores when testing attention and executive functions [modified card sorting test (p < 0.001) and digit span backward (p < 0.02)], as well as when testing constructive abilities [copy of complex designs (p = 0.001) and pentagon (p < 0.001)]. Using logistic regression analysis, diagnosis was predicted from the cognitive profile, with an overall accuracy of 88.2%. In addition, PDD patients showed a significantly higher Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore (p < 0.001) as well as higher UPDRS motor item scores [tremor at rest (p = 0.01) and bradykinesia (p = 0.001)]. CONCLUSIONS: The cognitive profile in PDD differs from that in DLB in the early stage of dementia, with worse performance on tests of attention and executive functions and constructive abilities in DLB compared to PDD patients. In contrast, motor symptoms are more severe in PDD than in DLB.

Cognitive Impairment and Brain Imaging Characteristics of Patients with Congenital Cataracts, Facial Dysmorphism, Neuropathy Syndrome.

Congenital cataracts, facial dysmorphism, neuropathy (CCFDN) syndrome is a complex autosomal recessive multisystem disorder. The aim of the current study is to evaluate the degree of cognitive impairment in a cohort of 22 CCFDN patients and its correlation with patients' age, motor disability, ataxia, and neuroimaging changes. Twenty-two patients with genetically confirmed diagnosis of CCFDN underwent a detailed neurological examination. Verbal and nonverbal intelligence, memory, executive functions, and verbal fluency wеre assessed in all the patients aged 4 to 47 years. Brain magnetic resonance imaging was performed in 20 affected patients. Eighteen affected were classified as having mild intellectual deficit, whereas 4 had borderline intelligence. In all psychometric tests, evaluating different cognitive domains, CCFDN patients had statistically significant lower scores when compared to the healthy control group. All cognitive domains seemed equally affected. The main abnormalities on brain MRI found in 19/20 patients included diffuse cerebral atrophy, enlargement of the lateral ventricles, and focal lesions in the subcortical white matter, different in number and size, consistent with demyelination more pronounced in the older CCFDN patients. The correlation analysis of the structural brain changes and the cognitive impairment found a statistically significant correlation only between the impairment of short-term verbal memory and the MRI changes.

Neurosyphilis with dementia and bilateral hippocampal atrophy on brain magnetic resonance imaging.

BACKGROUND: This article reports a rare case of active neurosyphilis in a man with mild to moderate dementia and marked hippocampal atrophy, mimicking early onset Alzheimer's disease. Few cases have so far described bilateral hippocampal atrophy mimicking Alzheimer's disease in neurosyphilis. CASE PRESENTATION: The patient presented here is a 33 year old Bulgarian male, whose clinical features include progressive cognitive decline and behavioral changes over the last 18 months. Neuropsychological examination revealed mild to moderate dementia (Mini Mental State Examination score was 16/30) with impaired memory and attention, and executive dysfunction. Pyramidal, and extrapyramidal signs, as well as dysarthria and impairment in coordination, were documented. Brain magnetic resonance imaging showed cortical atrophy with noticeable bilateral hippocampal atrophy. The diagnosis of active neurosyphilis was based on positive results of the Venereal Disease Research Laboratory test/Treponema pallidum hemagglutination reactions in blood and cerebrospinal fluid samples. In addition, cerebrospinal fluid analysis showed pleocytosis and elevated protein levels. High-dose intravenous penicillin therapy was administered. At 6 month follow up, improvements were noted clinically, on neuropsychological examinations, and in cerebrospinal fluid samples. CONCLUSION: This case underlines the importance of early diagnosis of neurosyphilis. The results suggest that neurosyphilis should be considered when magnetic resonance imaging results indicate mesiotemporal abnormalities and hippocampal atrophy. Neurosyphilis is a treatable condition which requires early aggressive antibiotic therapy.

Cognitive profile of the earliest stage of dementia in Parkinson's disease.

Recently, a strong interest has emerged in recognizing Parkinson's disease dementia (PDD) at a very early stage. However, the specific profile of the earliest stages of PDD is still unclear and a matter of considerable controversy. The objective of this study was to find out early neuropsychological markers for progression of dementia in this population. Fifty-eight patients with PDD were divided into 2 subgroups on the basis of the Mini-Mental State Examination: very mild and mild. The comparison with 26 normal controls shows that very mild PDD had deficits on attention/executive functions, naming, visuospatial/constructional abilities and retrieval of the episodic memory. Patients with mild PDD showed additional deficits on coding of episodic memory. Moreover, we found that in this early stage of PDD, the progression of dementia is mainly related to deterioration of attention/executive functions as well as retrieval and coding of episodic memory.

Cognitive dysfunction profile and arterial stiffness in type 2 diabetes.

BACKGROUND: The causative mechanisms of type 2 diabetes (T2D) on cognitive dysfunction are still undergoing development. AIM: To explore the cognitive dysfunction profile and its relation to the potential role of arterial stiffness in later middle age T2D patients. METHODS: We studied 37 patients with T2D (age range 45-65 years) and 22 normal controls. All participants underwent comprehensive neuropsychological assessment. The carotid-femoral pulse wave velocity (CF-PWV) measurements were taken with the PulsePen device. RESULTS: Our results showed significantly poorer performance on all tests assessing attention/executive functions and processing speed in patients with T2D. In addition to cognitive slowing T2D patients demonstrated significant deficits in almost all measures of verbal episodic memory after adjustment for age, education and blood pressure (BP) levels (p<0.05). Carotid-femoral pulse wave velocity (CF-PWV) appeared significantly higher in T2D subjects than in normal controls after adjustment for age and BP level (p<0.001). Significant relationship was observed between CF-PWV and cognitive status. CONCLUSION: We revealed that arterial stiffness was increased and associated with cognitive impairment in T2D. The cognitive profile indicates hippocampal amnestic type mild cognitive impairment associated with a pronounced dysexecutive syndrome suggesting that diabetes may affect cognition through both vascular and neurodegenerative processes. However, neurodegenerative cognitive profile caused by hippocampal atrophy in a pure vascular process could not be excluded.

ANO10 c.1150_1151del is a founder mutation causing autosomal recessive cerebellar ataxia in Roma/Gypsies.

A recent report (Vermeer et al. in Am J Hum Genet 87:813-819, 2010) implicated for the first time the ANO10 gene in the genetic basis of autosomal recessive cerebellar ataxias. One of the three described families were Roma/Gypsies from Serbia, where the affected individuals were homozygous for the truncating p.Leu384fs mutation and displayed distinct phenotypic features (Vermeer et al. in Am J Hum Genet 87:813-819, 2010). Based on the history and population genetics of the Roma/Gypsies, we hypothesised that p.Leu384fs could be another founder mutation in this population, whose identification in a larger number of genetically homogeneous patients will contribute to defining the phenotypic spectrum of the disorder. Here, we describe additional patients from neighbouring Bulgaria, outlining invariable ANO10-ataxia features and confirming global intellectual decline as part of the phenotype resulting from complete Anactomin 10 deficit.

Executive functions deficit in Parkinson's disease with amnestic mild cognitive impairment.

Recent studies suggest that onset of dementia in Parkinson's disease (PD) is preceded by a phase known as mild cognitive impairment (MCI). Different clinical subtypes of MCI in PD were found. The objective of this study was to investigate whether patients with PD diagnosed with amnestic MCI (aPD-MCI) have also subtle deficits in other cognitive domains and especially in attention/executive functions and, therefore to clarify whether all subcomponents of executive control are equally affected in aPD-MCI. We investigated 23 patients with aPD-MCI (modified Petersen's criteria) and 25 normal controls. Relative to controls, the aPD-MCI group showed significant deficits with reference to tasks that encompass various aspects of attention/executive functions, including Trail Making Test, Stroop test, Modified Card Sorting Test, and digit span backward, as well as phonemic and semantic verbal fluency. This suggests that executive dysfunction is consistently presented in PD with MCI, even in ''amnestic'' PD-MCI due to cortical-subcortical dysfunction.

Neurosyphilis presenting with dementia, chronic chorioretinitis and adverse reactions to treatment: a case report.

Neurosyphilis results from infection of the brain, meninges or spinal cord by Treponema pallidum and develops in about 25%-40% of persons who are not treated for syphilis. This article reports a rare case of active neurosyphilis with mild dementia, chronic chorioretinitis, and hearing loss. During the treatment with Penicillin, a rare combination of complications such as Jarisch-Herxheimer and Hoigné reactions were observed.The clinical feature is characterized by a slow progressive cognitive decline and behavior changes for the last 2 years. Neuropsychological examination revealed mild dementia (MMSE = 23) with impaired memory and attention and executive function. Left sided chronic chorioretinitis and hearing loss were documented. High dose intravenous penicillin therapy was complicated by Jarisch-Herxheimer and Hoigne reactions. During the follow up examinations at 6 and 12 months, the clinical signs, neuropsychological examination, and cerebrospinal fluid (CFS) samples showed improvement of dementia, CSF findings, and hydrocephalus.In conclusion, this atypical presentation of neurosyphilis in combination with rare complications of treatment is worthy of attention. Neurosyphilis should be part of the differential diagnosis of each patient showing cognitive deterioration and behaviour disturbances.

Novel PSEN1 mutation in a Bulgarian patient with very early-onset Alzheimer's disease, spastic paraparesis, and extrapyramidal signs.

We describe the phenotype of a Bulgarian early-onset Alzheimer's disease (EOAD) family with 3 affected patients in 3 generations. In the proband, a novel L381V mutation in the presenilin1 (PSEN1) gene was identified. In this patient, the first symptoms were noticed at the age of 32 years and she died at the age of 37 years. The EOAD phenotype caused by the novel L381V mutation in the PSEN1 gene presented clinically, by a very early onset in the proband, rapid progression of dementia, spastic paraparesis, and extrapyramidal signs, as atypical clinical signs in Alzheimer's disease patients.

Familial generalized epilepsy in Bulgarian Roma.

AIMS: Gypsy communities constitute cultural and frequently inbred genetic isolates. Several genetic neurological disorders have been identified in these communities. Epilepsy appears as a fairly frequent medical condition among Bulgarian Gypsies, and many patients can be related to large pedigrees that may then be studied by conventional genetic linkage analyses. PATIENTS AND METHODS: We identified two large Wallachian Gypsy families from the Plovdiv and Varna regions of Bulgaria, with detailed clinical questionnaires and examination, and EEG recordings for many. Genetic linkage analysis was performed using microsatellite markers spaced across the human genome. RESULTS: Although phenotypes were not always easy to identify, epilepsy appears in both families as a dominant, or pseudo-dominant trait, with the characteristics of idiopathic generalized epilepsy with onset at various ages, with infrequent, generalized tonic-clonic seizures, some associated with fever in childhood, but without sensitivity to fever in later life. While few markers yielded LOD scores > 2, no locus showed significant linkage, assuming autosomal dominant or recessive modes of inheritance. CONCLUSION: Idiopathic generalized epilepsy, with a marked familial character, has not been reported to date in Bulgarian Gypsies. Both pedigrees studied here present with an identifiable epilepsy type inherited as a Mendelian trait. Despite the current lack of significant linkage, these families may constitute interesting ground for further genetic studies, on condition that more patients and families can be recruited. [Published with supplemental data on DVD].

Impaired decision-making in psychopathic heroin addicts.

Substance-dependent individuals (SDIs) often show neurocognitive deficits in decision-making, such that their choices are biased toward the greatest immediate reward rather than the optimal future outcome. However, studies of SDIs are often hampered by two significant methodological challenges: polysubstance dependence and comorbid conditions, which are independently associated with neurocognitive impairments. We addressed these methodological challenges by testing heroin addicts in Bulgaria, where heroin addiction is highly prevalent but polysubstance dependence is rare. The goal of the current study was to evaluate the potential contribution of psychopathy to decision-making processes among this group of Bulgarian heroin addicts. We tested 78 male currently abstaining heroin addicts, classified as psychopathic or non-psychopathic using the Hare Psychopathy Checklist, Revised (PCL-R). Psychopathic heroin addicts showed notable deficits in decision-making in that they made significantly more disadvantageous decisions relative to non-psychopathic heroin addicts. Results indicate that the presence of psychopathy may exacerbate decision-making deficits in heroin addicts.