Translating NIA-AA criteria into usual practice: Report from the ReDeMa Project.

INTRODUCTION: Biomarker-informed criteria were proposed for the diagnosis of Alzheimer's disease (AD) by the National Institute on Aging and the Alzheimer's Association (NIA-AA) in 2011; however, the adequacy of this criteria has not been sufficiently evaluated. METHODS: ReDeMa (Red de Demencias de Madrid) is a regional cohort of patients attending memory and neurology clinics. Core cerebrospinal fluid biomarkers were obtained, NIA-AA diagnostic criteria were considered, and changes in diagnosis and management were evaluated. RESULTS: A total of 233 patients were analyzed (mean age 70 years, 50% women, 73% AD). The diagnostic language was modified significantly, with a majority assumption of NIA-AA definitions (69%). Confidence in diagnosis increased from 70% to 92% (p < 0.0005) and management was changed in 71% of patient/caregivers. The influence of neurologist's age or expertise on study results was minimal. DISCUSSION: The NIA-AA criteria are adequate and utile for usual practice in memory and neurology clinics, improving diagnostic confidence and significantly modifying patient management. HIGHLIGHTS: Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers increase diagnostic certainty regardless of the neurologist.AD CSF biomarkers lead to changes in disease management .Biomarker-enriched, 2011 NIA-AA diagnostic criteria are adequate for usual practice.

Bilingualism in Primary Progressive Aphasia: A Retrospective Study on Clinical and Language Characteristics.

BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive deterioration of language. Being rare, reports of PPA in multilingual individuals are scarce, despite more than half of the world population being multilingual. METHODS: We describe clinical characteristics of 33 bilingual patients with PPA, including symptom presentation and language deficits pattern in their first (L1) and second language (L2), through a systematic literature review and new cases retrospectively identified in 5 countries. RESULTS: In total, 14 patients presented with nonfluent/agrammatic variant, 6 with semantic variant, and 13 with logopenic variant, with a median symptom onset of 2 years. Word-finding difficulties was the first symptom in 65% of all cases, initially noticed in L2, and not always the dominant language. Our group had 22 different languages as L1, and 9 as L2. At the whole-group level there was a tendency for parallel impairment in both languages, in line with the shared bilingual neural substrate hypothesis, but each PPA variant showed some heterogeneity. DISCUSSION: Each PPA variant showed heterogeneity, showing the need for comprehensive language and cognitive assessment across languages, as well as further clarification on the role of language mediators.

Disability subtypes and mortality rates in older adults: A longitudinal population-based study (NEDICES).

OBJECTIVE: We investigated the mortality rates of three subtypes of disability and their specific explanatory factors in older adults. METHODS: Our data come from NEDICES, a population-based longitudinal cohort study of Spanish older adults. We examined 3816 participants without dementia who completed the Pfeffer's Functional Activities Questionnaire (FAQ) and an assessment of self-perceived functional limitations (SFL) associated with health conditions. Subjects were classified into mutually exclusive subtypes of disability: subtype 1 (SFL), subtype 2 (impaired FAQ), and subtype 3 (impaired FAQ plus SFL). Factors related to all disability subtypes were analyzed using a multinomial logistic regression (MLR), whereas Cox regression (CR) models adjusted by covariates were applied to compare survival rates between groups at the 5-year follow up. RESULTS: The CR models indicated that SFL and FAQ scores were associated with higher risk of mortality at 5-years. After stratifying by subtypes of disability, mortality was significantly higher in subtype 3 than in subtypes 1 and 2. All models were consistent after adjusting by different covariates. The MLR showed that subtype 1 was specifically associated with the number of comorbidities, whereas subtype 2 was associated with lower MMSE scores depression and living in nursing homes. CONCLUSIONS: Our results show that the combination of impaired FAQ plus SFL have an increased differential predictive utility for mortality than approaches based on unique measures. They also indicate that both measures of disability are associated with different explanatory factors.

High education accelerates cognitive decline in dementia: A brief report from the population-based NEDICES cohort.

High education has been associated with faster cognitive decline after diagnosis of Alzheimer's disease (AD), but it is unclear whether these findings extend to other dementia subtypes. OBJECTIVE: We investigated whether educational attainment influences the cognitive trajectories of older adults with different dementia subtypes. METHODS: All participants were selected from NEDICES, a prospective population-based cohort study of Spanish older adults. A total sample of 53 individuals with dementia completed the MMSE-37 at Times 1 and 2 (mean follow-up=2.8±0.5 years) to assess cognitive decline. RESULTS: At follow-up, MMSE-37 scores had decreased by 3.34±4.98 points in low-educated individuals with dementia versus 7.90±4.88 points in high-educated subjects (effect size (r)=0.32, p=0.02). CONCLUSION: Educational level influenced the cognitive trajectories of patients with dementia assessed by the MMSE-37.

A educação mais alta tem sido associada com um declínio cognitive mais rápido após o diagnóstico de doença de Alzheimer (DA), mas não está claro se estes achados podem ser extendidos a outros subtipos de demência. OBJETIVO: Nós investigamos se o nível educacional alcançado influencia as trajetórias cognitivas de adultos idosos com diferentes subtipos de demência. MÉTODOS: Todos os participantes foram selecionados do NEDICES, um estudo de coorte prospectivo de base populacional de idosos adultos espanhóis. Uma amostra total de 53 indivíduos com demência completaram o MEEM-37 nos momentos 1 e 2 (acompanhamento médio de 2.8± 0.5 anos) para avaliação do declínio cognitive. RESULTADOS: No seguimento, o MEEM-37 declinou 3.34±4.98 pontos em indivíduos de baixa escolaridade com demência versus 7.90±4.88 pontos entre os altamente escolarizados (tamanho do efeito (r)=0.32, p=0.02). CONCLUSÃO: O nível educacional influenciou as trajetórias cognitivas de pacientes com demência avaliados pelo MEEM-37.

High education accelerates cognitive decline in dementia: A brief report from the population-based NEDICES cohort / Maior educação acelera o declínio cognitive em demência: relato breve da coorte de base populacional NEDICES

ABSTRACT High education has been associated with faster cognitive decline after diagnosis of Alzheimer's disease (AD), but it is unclear whether these findings extend to other dementia subtypes. OBJECTIVE: We investigated whether educational attainment influences the cognitive trajectories of older adults with different dementia subtypes. METHODS: All participants were selected from NEDICES, a prospective population-based cohort study of Spanish older adults. A total sample of 53 individuals with dementia completed the MMSE-37 at Times 1 and 2 (mean follow-up=2.8±0.5 years) to assess cognitive decline. RESULTS: At follow-up, MMSE-37 scores had decreased by 3.34±4.98 points in low-educated individuals with dementia versus 7.90±4.88 points in high-educated subjects (effect size (r)=0.32, p=0.02). CONCLUSION: Educational level influenced the cognitive trajectories of patients with dementia assessed by the MMSE-37.

RESUMO A educação mais alta tem sido associada com um declínio cognitive mais rápido após o diagnóstico de doença de Alzheimer (DA), mas não está claro se estes achados podem ser extendidos a outros subtipos de demência. OBJETIVO: Nós investigamos se o nível educacional alcançado influencia as trajetórias cognitivas de adultos idosos com diferentes subtipos de demência. MÉTODOS: Todos os participantes foram selecionados do NEDICES, um estudo de coorte prospectivo de base populacional de idosos adultos espanhóis. Uma amostra total de 53 indivíduos com demência completaram o MEEM-37 nos momentos 1 e 2 (acompanhamento médio de 2.8± 0.5 anos) para avaliação do declínio cognitive. RESULTADOS: No seguimento, o MEEM-37 declinou 3.34±4.98 pontos em indivíduos de baixa escolaridade com demência versus 7.90±4.88 pontos entre os altamente escolarizados (tamanho do efeito (r)=0.32, p=0.02). CONCLUSÃO: O nível educacional influenciou as trajetórias cognitivas de pacientes com demência avaliados pelo MEEM-37.

Impact of literacy and years of education on the diagnosis of dementia: A population-based study.

BACKGROUND: The effect of different educational indices on clinical diagnosis of dementia requires more investigation. OBJECTIVE: We compared the differential influence of two educational indices (EIs): years of schooling and level of education (i.e., null/low literacy, can read and write, primary school, and secondary school) on global cognition, functional performance, and the probability of having a dementia diagnosis. METHOD: A total of 3,816 participants were selected from the population-based study of older adults "Neurological Disorders in Central Spain" (NEDICES). The 37-item version of the Mini-Mental State Examination (MMSE-37) and the Pfeffer's questionnaire were applied to assess cognitive and functional performance, respectively. The diagnosis of dementia was performed by expert neurologists according to Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria. Logistic regression models adjusted for potential confounders were carried out to test the association between the two EIs and dementia diagnosis. RESULTS: Both EIs were significantly associated with cognitive and functional scores, but individuals with null/low literacy performed significantly worse on MMSE-37 than literates when these groups were compared in terms of years of schooling. The two EIs were also related to an increased probability of dementia diagnosis in logistic models, but the association's strength was stronger for level of education than for years of schooling. CONCLUSION: Literacy predicted cognitive performance over and above the years of schooling. Lower education increases the probability of having a dementia diagnosis but the impact of different EIs is not uniform.

Accuracy of a Brief Neuropsychological Battery for the Diagnosis of Dementia and Mild Cognitive Impairment: An Analysis of the NEDICES Cohort.

Early separation of mild cognitive impairment (MCI) from normal aging and mild cases of dementia remains a challenge, especially in the general population. We aimed to analyze the diagnostic accuracy of a brief neuropsychological battery (BNB) in dementia and MCI cases from the Neurological Disorders in Central Spain (NEDICES) population-based cohort study. We screened 3,891 participants into dementia and non-dementia groups using a two-phase procedure: screening (MMSE-37 and Pfeffer-11) and clinical diagnosis by specialists (DSM-IV criteria). We selected subsequently a subsample of dementia (n = 98), MCI (n = 71), and cognitively healthy (n = 123) participants matched in socio-demographic characteristics. The clinical validity of each test of the BNB was determined by the area under the ROC curve. We determined the best combination of tests to classify individuals into the diagnostic groups by logistic regression analyses. The results indicated that dementia and MCI groups could be best discriminated from the healthy control group on the basis of their scores on the semantic verbal fluency and delayed recall subtests of the BNB. As for discriminating the MCI group from the dementia group, immediate recall tasks (stories and pictures) yielded the highest level of accuracy. Probably the most interesting finding is that the verbal fluency task consistently allowed discrimination among the diagnostic groups. Overall, subtests of the BNB are more accurate in differentiating dementia patients than MCI patients from healthy controls. In this population-based sample, a more fine-grained discrimination that includes MCI patients should follow a systematic subtest-wise analysis and decision.

Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer's Disease Patients.

Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer's disease (AD) by clearing brain amyloid ß-peptide (Aß) across the blood-cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aß is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aß in the CSF could be associated with defective clearance of Aß and an increase of brain Aß levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aß-related pathologies in AD.

The ability of self-rated health to predict mortality among community-dwelling elderly individuals differs according to the specific cause of death: data from the NEDICES cohort.

BACKGROUND: The biomedical and psychosocial mechanisms underlying the relationship between self-rated health (SRH) and mortality in elderly individuals remain unclear. OBJECTIVE: To assess the association between different measurements of subjective health (global, age-comparative, and time-comparative SRH) and cause-specific mortality. METHODS: Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of the prevalence and incidence of major age-associated conditions. Data on demographic and health-related variables were collected from 5,278 subjects (≥65 years) in the baseline questionnaire. Thirteen-year mortality and cause of death were obtained from the National Death Registry. Adjusted hazard ratios (aHR) for SRH and all-cause and cause-specific mortality were estimated by Cox proportional hazard models. RESULTS: At baseline, 4,958 participants (93.9%) answered the SRH questionnaire. At the end of follow-up, 2,468 (49.8%) participants had died, of whom 723 (29.2%) died from cardiovascular diseases, 609 (24.7%) from cancer, and 359 (14.5%) from respiratory diseases. Global SRH independently predicted all-cause mortality (aHR for 'poor or very poor' vs. 'very good' category: 1.39; 95% confidence interval (CI): 1.15-1.69). Analysis of cause-specific mortality revealed that global SRH was an independent predictor for death due to respiratory diseases (aHR for 'poor or very poor' vs. 'very good' category: 2.61; 95% CI: 1.55-4.39), whereas age-comparative SRH exhibited a gradient effect on the risk of death due to stroke. Time-comparative SRH provided small additional predictive value. CONCLUSIONS: The predictive ability of SRH for mortality largely differs according to the specific cause of death, with the strongest associations found for respiratory disease and stroke mortality.

Retinal nerve fiber layer thinning in dementia associated with Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease.

Optical coherence tomography is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL). Previous studies have shown that degenerative changes occur in optic nerve fibers and are manifested as thinning of RNLF in patients with Alzheimer's disease (AD). However, there are no studies on the thickness of the RNLF in other types of dementia, such as dementia with Lewy bodies and dementia associated with Parkinson's disease. In this study, patients fulfilling diagnostic for AD (n = 10), dementia with Lewy bodies (n = 10), dementia associated with Parkinson's disease (n = 10), and cognitively normal age-matched controls (n = 10) underwent optical coherence tomography examinations to measure RNLF thickness. There was a significant decrease in RNLF thickness in each type of dementia compared to the control group (Mann-Whitney test, all p < 0.001). Although patients with dementia with Lewy bodies may have a greater thinning than both patients with AD and dementia associated with Parkinson's disease, the differences were statistically nonsignificant (Kruskal-Wallis test, p = 0.525). The thickness of the RNLF correlated significantly (p < 0.001) with both the Mini-Mental State Examination and the Mattis Dementia Rating Scale scores in all types of dementia; that is to say, the greater the cognitive deterioration, the greater the reduction of thickness of the RNLF. The findings from this study show that retinal involvement measured by optical coherence tomography may also be present in non-AD dementias.

Rate of cognitive decline in premotor Parkinson's disease: a prospective study (NEDICES).

Previous research has documented cognitive impairment in the early stages of Parkinson's disease (PD). It is not known when this decline starts or if decline progresses at an accelerated rate during the premotor period of the disorder. In this population-based prospective study of older people (≥65 years) from the Neurological Disorders in Central Spain (NEDICES) cohort, we compared the rates of cognitive decline in 3 groups: (1) non-PD elderly controls; (2) prevalent PD patients (those diagnosed with the disease at baseline, 1994-95); and (3) premotor PD subjects (those diagnosed with the disease at follow up, 1997-98, but not at baseline). A 37-item version of the Mini-Mental State Examination (37-MMSE) was administered in the 2 visits of the study. From 2487 participants (age, 72.8 ± 6.0 years), including 2429 controls, we recruited 21 premotor PD cases, and 37 prevalent PD cases. At baseline, the mean 37-MMSE score was 28.5 ± 4.7 in prevalent cases, 28.1 ± 4.6 in premotor cases, and 29.9 ± 5.0 in controls (P = .046). During the 3-year follow-up period, there was a significant score decline of 2.4 ± 4.6 points in prevalent cases versus 0.2 ± 4.1 points in premotor cases and 0.3 ± 4.0 points in controls (Kruskal-Wallis test, P = .03). In the NEDICES cohort, cognitive test scores of prevalent PD cases declined at a rate above and beyond that observed in premotor PD cases and in controls. The rate of cognitive decline in premotor PD and controls was similar. Our data suggest that a decline in global cognitive function does not occur in premotor PD.

Calmodulin levels in blood cells as a potential biomarker of Alzheimer's disease.

INTRODUCTION: The clinical features of Alzheimer's disease (AD) overlap with a number of other dementias and conclusive diagnosis is only achieved at autopsy. Accurate in-life diagnosis requires finding biomarkers suitable for early diagnosis, as well as for discrimination from other types of dementia. Mounting evidence suggests that AD-dependent processes may also affect peripheral cells. We previously reported that calmodulin (CaM) signaling is impaired in AD lymphoblasts. Here, we address the issue as to whether the assessment of CaM levels in peripheral cells could serve as a diagnostic biomarker. METHODS: A total of 165 subjects were enrolled in the study, including 56 AD patients, 15 patients with mild cognitive impairment, 7 with frontotemporal dementia associated with progranulin mutations, 4 with dementia with Lewy bodies, 20 patients with Parkinson's disease, 10 with amyotrophic lateral sclerosis, 5 with progressive supranuclear palsy, and 48 cognitively normal individuals. CaM levels were then analyzed in lymphoblasts, peripheral blood mononuclear cells and plasma. Receiver operating characteristic (ROC) curve analyses were employed to evaluate the diagnostic performance of CaM content in identifying AD patients. RESULTS: Compared with control individuals, CaM levels were significantly increased in AD cells, but not in the other neurodegenerative disorders. CaM levels differentiated AD from control with a sensitivity of 0.89 and a specificity of 0.82 and were not dependent on disease severity or age. MCI patients also showed higher levels of the protein. CONCLUSIONS: CaM levels could be considered a peripheral biomarker for AD in its early stage and help to discriminate from other types of dementia.

Mortality from Parkinson's disease: a population-based prospective study (NEDICES).

Most studies of mortality in Parkinson's disease have been clinical studies, yielding results that are not representative of the general population. We assessed the risk of mortality from Parkinson's disease in the Neurological Disorders in Central Spain (NEDICES) study, a prospective population-based study in which Parkinson's disease patients who were not ascertained through medical practitioners were also included. The cohort consisted of 5262 elderly subjects (mean baseline age, 73.0 years), including 81 with Parkinson's disease at baseline (1994-1995). Thirteen-year mortality was assessed. Two thousand seven hundred and one of 5262 subjects (51.3%) died over a median follow-up of 12.0 years (range, 0.04-14.8 years), including 66 of 81 subjects (81.5%) with Parkinson's disease at baseline and 2635 of 5181 subjects (50.8%) without Parkinson's disease at baseline. In an unadjusted Cox model, the hazard ratio of mortality was increased in subjects with Parkinson's disease (hazard ratio, 2.29; 95% confidence interval, 1.80-2.93; P < .001) versus subjects without Parkinson's disease (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, the risk of mortality remained elevated in subjects with Parkinson's disease (hazard ratio, 1.75; 95% CI, 1.32-2.31, P < .001). In additional Cox models, Parkinson's disease patients with dementia had particularly high risks of mortality (adjusted hazard ratio, 2.62; 95% CI, 1.40-4.90; P < .001). In this prospective population-based study, Parkinson's disease was an independent predictor of mortality in the elderly. Parkinson's disease patients with dementia had particularly high risks of mortality.

Population-based case-control study of cognitive function in early Parkinson's disease (NEDICES).

BACKGROUND: Population-based assessments of cognitive function in patients with early Parkinson's disease (PD) are rare. We examined whether patients with early PD have cognitive deficits when compared with matched controls METHODS: All participants were age 65 years or older (median=76 years) and were enrolled in the Neurological Disorders in Central Spain (NEDICES) study in central Spain. We identified all participants with early PD (<5 years duration) (N=46). These were matched to 138 controls. Neuropsychological test scores were compared in PD patients vs. controls. In logistic regression models, we adjusted for the effects of confounding variables. In these models, the dependent variable was the neuropsychological test score (lowest quartile vs. all other quartiles) and the independent variable was PD vs. control. RESULTS: Sixteen of 46 patients (34.8%) with early PD were previously undiagnosed. Subjective memory complaint was present in 27 (58.7%) PD patients vs. 51 (37.0%) controls (p=0.010). In logistic regression models that adjusted for gender, education, and depressive symptoms or antidepressant use, PD patients performed less well on the 37-item version of the Mini-Mental State Examination (p=0.04), animal (p<0.001) and fruit fluency (p=0.04) as well as in a delayed free recall memory test (p=0.04) than controls. CONCLUSIONS: In this population-based sample of older patients with early PD, the rate of subjective and object cognitive impairment was appreciable. Patients with PD of less than five years duration performed relatively poorly on tests of global cognition, verbal fluency and memory. Clinicians should be vigilant to these cognitive difficulties even in the early stages of PD.

Dementia-associated mortality at thirteen years in the NEDICES Cohort Study.

To evaluate the mortality, thirteen years after the baseline wave (1994), of participants suffering dementia in the Neurological Disorders in Central Spain (NEDICES) Cohort Study, we conducted a population-based cohort study in the elderly (65 years and more) with 5,278 screened participants at baseline. Mortality has been evaluated by means of the National Death Registry of Spain at 1-5-2007, 13 years after enrolment. Cox's proportional hazards regression models were used to evaluate the hazard of death according to dementia severity and type, adjusting for potential covariates (gender, age, level of education, and co-morbidity). Survival was estimated using Kaplan-Meier method. Of the 5,278 participants screened at baseline, 306 had dementia. Mortality at 13 years was: 275 deaths (89.9%) in dementia subjects; and 2,426 (49.0%) in subjects without dementia. Mortality was higher and statistically significant in dementia subjects. The degree of dementia (DSM-III-R) correlated with the risk of mortality, from mild (HR = 2.23; CI: 1.77-2.82) to moderate (HR =3.10; CI: 2.47-3.89) and severe dementia (HR = 4.98; CI: 3.85-6.44). Survival was similar in Alzheimer's disease and vascular dementia. Factors associated with higher mortality in Cox proportional hazard models were older age, male gender, and comorbidity. Using Population Attributable risk (PAR%), dementia was related to 11.3% of all deaths. Dementia intensity increases the mortality risk at ten years in the NEDICES Study as in other cohort studies. Age, gender, and co-morbidity are associated with higher mortality in dementia patients. Almost one third of deaths in persons over 85 years-old could be attributable to dementia.

Premotor cognitive status in a cohort of incident Parkinson disease patients (NEDICES).

BACKGROUND: A variety of symptoms may precede the classical motor features of Parkinson disease (PD). However, it is not known whether cognitive dysfunction precedes the motor phase of PD. We examined whether patients with incident PD had had global cognitive function disturbances three years prior to diagnosis when compared with matched controls in a cohort of community-dwelling subjects. METHODS: All participants were age 65 years or older (median 76 years) and were enrolled in the Neurological Disorders in Central Spain (NEDICES) study in central Spain. We identified all participants with incident PD (N=23), diagnosed in the follow-up examination (1997-1998), who had performed an expanded 37-item version of the Mini-Mental State Examination (37-MMSE) at the baseline evaluation (1994-1995). These 23 were 1:4 matched to 92 controls. RESULTS: Baseline 37-MMSE scores were 27.9±4.9 (28) in PD patients and 28.7±6.5 (31) in controls (p=0.212). There were no patient-control differences in orientation, immediate recall, attention and calculation, memory recall, language, or visuospatial copying. In analyses that adjusted for several possible confounding factors, there were no case-control differences. CONCLUSIONS: In this population-based sample, patients with incident PD did not have evidence of significant global cognitive function disturbances three years prior to their diagnosis when compared with matched controls. Our data suggest that global cognitive dysfunction does not precede the diagnosis of PD.

Mirrored-self misidentification in a patient without dementia: evidence for right hemispheric and bifrontal damage.

Mirrored-self misidentification, often referred as the 'mirror sign', is a delusion characterized by the inability to recognize one's own reflected image, often associated with the intact capacity to recognize others in the mirror. It has been described mainly in moderate or severe dementia, especially Alzheimer's disease. In the few reported cases without global cognitive impairment, right hemispheric and frontal dysfunctions have been described. We report a 90-year-old man with abrupt onset of the mirror sign after a minor right hemispheric ischemic stroke. Neuropsychological testing revealed preserved cognitive capacities, except for mild to moderate impairment of visuospatial skills, suggesting right hemisphere dysfunction. Neuroimaging showed a small right dorsolateral frontal infarct, and bifrontal encephalomalacia, consistent with a past history of head trauma. Scattered ischemic white matter lesions in posterior periventricular regions were also seen. It seems that the mirror sign is a multifactorial phenomenon that usually requires right hemispheric dysfunction (perceptual abnormalities, loss of familiarity) and frontal damage (loss of judgement and inability to correct wrong beliefs). The right frontal dorsolateral prefrontal cortex seems to have a crucial role in self-recognition.

Memory impairment in a simple recall task increases mortality at 10 years in non-demented elderly.

OBJECTIVE: To evaluate whether memory impairment detected in the three-word delayed recall task of the Mini-Mental State Examination (MMSE) increases the risk of mortality. METHODS: The NEDICES (Neurological Diseases in Central Spain) cohort study, is a population census-based study, aimed at detecting age-associated neurological diseases in people aged 65 and over, living in one rural and two urban communities in central Spain. Participants with dementia or without MMSE evaluation at baseline were excluded. Mortality was evaluated 10.67 years after enrollment. Cox's proportional hazards regression models were used to evaluate the hazard of death according to performance in the three-word delayed recall task included in the MMSE (score 0-3), adjusting for potential covariates (sex, age, level of education, and comorbidity). Survival was estimated using Kaplan-Meier method. RESULTS: The final study population comprised 3778 non-demented elderly subjects. After adjusting for confounding covariates, mortality was 52% greater in persons with the lowest memory score (0) vs. persons with the highest score (3). Hazard ratios (HR) showed a tendency to an increase in mortality from the highest to the lowest memory score, which was statistically significant for the groups with none (HR=1.52; CI=1.27-1.80) or one (HR=1.24; CI=1.04-1.48) word recall. Older age, male sex, and comorbidity were also associated with mortality, but level of education was not. CONCLUSIONS: Memory impairment in the three-word delayed free recall, a very simple task used by physicians worldwide, increases the risk of mortality at 10 years in non-demented elderly.

Risk of incident dementia in drug-untreated arterial hypertension: a population-based study.

Arterial hypertension in midlife may increase the risk of late-life dementia. Notably, there is conflicting data as to whether hypertension in the elderly (age 65 years and older) is a risk factor for dementia and Alzheimer's disease (AD). We determined whether drug-untreated hypertension was associated with a higher risk of incident dementia and AD. In a population-based study of older people in central Spain (NEDICES), non-demented participants were followed prospectively. Dementia at follow-up was diagnosed using DSM-IV criteria. Using Cox proportional hazards models, the risk of dementia was estimated in participants with drug-untreated hypertension and in participants with drug-treated hypertension versus controls. The 3,824 participants had a mean duration of follow-up of 3.2 years. Sixty-two (3.3%) of 1,870 participants without baseline hypertension developed incident dementia versus 78 (4.7%) of 1,657 with drug-treated, baseline hypertension and 19 (12.0%) with drug-untreated, baseline hypertension. In an unadjusted Cox model, risk of dementia was increased in participants with drug-untreated hypertension (relative risk [RR] =1.93, 95% confidence interval [CI]=1.15­3.23, p = 0.01) and in participants with drug-treated hypertension (RR =1.43, 95% CI= 1.02­2.0, p =0.035) versus participants without hypertension (reference group). In a fully adjusted Cox model, the risk of dementia remained increased in participants with drug-untreated hypertension (RR =2.38, 95% CI =1.32­4.29, p=0.004). Results were similar for risk of AD. Our results suggest that drug-untreated hypertension may be an independent risk factor for dementia and AD in the elderly.

A variant of WEBINO syndrome after top of the basilar artery stroke.

Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is an uncommon neuro-ophthalmologic syndrome consisting of both eyes primary position exotropia and bilateral internuclear ophthalmoplegia. It is thought to be caused by medial midbrain lesions involving both bilateral medial longitudinal fasciculi and medial rectus subnuclei. We report the clinical and neuroimaging findings of a WEBINO syndrome associated to bilateral ptosis, non-reactive mydriasis and complete vertical gaze palsy in a 55-year-old man who suffered a top of the basilar artery stroke causing tegmental midbrain infarction.