Adult Attention Deficit-Hyperactivity Disorder is associated with Lewy Body Disease and Cognitive Impairment: A prospective cohort Study With 15-year Follow-Up.

OBJECTIVES: Past reports have suggested that attention-deficit/hyperactivity disorder (ADHD) may be a risk factor for Lewy body disease (LBD). To confirm this relationship, we conducted the present study. DESIGN: A prospective observational cohort study with a follow-up to 15 years. SETTING: The subjects were recruited from cognitive neurology clinics, where they attended for a cognitive complaint or health check-up. PARTICIPANTS: Two groups of subjects: ADHD adults and healthy subjects. MEASUREMENTS: The risk of dementia and LBD was estimated with Kaplan-Meier analysis comparing for the presence or absence of ADHD with the log-rank test. Predictors of conversion were assessed through separate univariate and multivariate Cox regression analyses, adjusting for several variables. RESULTS: The baseline sample consisted of 161 subjects with ADHD and 109 without ADHD. At the end of the follow-up, 31 subjects developed dementia, 27 cases in the ADHD group and 4 in comparison group. Dementia with Lewy bodies (DLB) was the most frequent type (N:20) of which 19 corresponded to the ADHD group. The incidence of non-amnestic-MCI in the ADHD group was higher representing 67.1 % of these subjects (N:108), and 17.4% (N:19) of healthy cases. The hazard ratios for dementia and LBD in the multivariate adjusted model were 3.33 (95% CI 1.0915 to 10.1699) and 54.54 (95% CI 7.4849 to 397.5028), respectively in the ADHD group. CONCLUSIONS: This study showed that adult ADHD is independently associated with an increased risk of LBD, dementia, and na-MCI. Future studies should clarify this relationship to develop preventive measures for these patients.

Validity and reliability of the Turkish version of the ALBA screening instrument for Lewy body dementia in older adults.

ALBA screening instrument (ASI) has been demonstrated to be an effective, cheap, and noninvasive clinical instrument to screen for Lewy body dementia (LBD). We aimed to determine the validity and reliability of the Turkish version of ASI (ASI-T) in patients with LBD and to investigate the discriminative power of the test in patients with Alzheimer's Disease (AD), LBD, and cognitively healthy older adults (controls). 172 older adults over 60 years of age (43 with LBD, 41 AD, and 88 controls) were included. The sensitivity and specificity of the instrument were determined. A significant difference was found in ASI-T total score between people with LBD versus the controls (t=-9.259; p < 0.001), and versus patients with AD (t = 3.490; p = 0.001). Internal consistency of the ASI-T was good(Cronbach's alpha = 0.81). The cutoff score of 7 showed sensitivity (86%) and specificity (81%) (AUC= 0.888,CI0.95, p < 0.001) compared to controls. Also, compared to AD, it showed sensitivity (86%) and specificity(70%) (AUC = 0.590,CI .95, p < 0.001). Moreover, ASI-T demonstrated a significant concurrent validity with MMSE (r = -0.62; p < 0.001) and MoCA (r = -0.54; p = 0.003). In factor analysis, the five subscales accounted for 60% of the total variance. Our findings suggested that the ASI-T is a reliable, valid, and effective instrument for screening LBD. With acceptable psychometric properties, it has the power to distinguish patients with LBD from controls or those with AD.

Thalamus volume change and cognitive impairment in early relapsing-remitting multiple sclerosis patients.

Aims The objective of the study was to assess whether changes in the volume of the thalamus during the onset of multiple sclerosis predict cognitive impairment after accounting for the effects of brain volume loss. Methods A prospective study included patients with relapsing-remitting multiple sclerosis less than 3 years after disease onset (defined as the first demyelinating symptom), Expanded Disability Status Scale of 3 or less, no history of cognitive impairment and at least 2 years of follow-up. Patients were clinically followed up with annual brain magnetic resonance imaging and neuropsychological evaluations for 2 years. Measures of memory, information processing speed and executive function were evaluated at baseline and follow-up with a comprehensive neuropsychological test battery. After 2 years, the patients were classified into two groups, one with and the other without cognitive impairment. Brain dual-echo, high-resolution three-dimensional T1-weighted magnetic resonance imaging scans were acquired at baseline and every 12 months for 2 years. Between-group differences in thalamus volume, total and neocortical grey matter and white matter volumes were assessed using FIRST, SIENA, SIENAXr, FIRST software (logistic regression analysis P < 0.05 significant). Results Sixty-one patients, mean age 38.4 years, 35 (57%) women were included. At 2 years of follow-up, 17 (28%) had cognitive impairment. Cognitive impairment patients exhibited significantly slower information processing speed and attentional deficits compared with patients without cognitive impairment ( P < 0.001 and P = 0.02, respectively). In the cognitive impairment group a significant reduction in the percentage of thalamus volume ( P < 0.001) was observed compared with the group without cognitive impairment. Conclusion We observed a significant decrease in thalamus volume in multiple sclerosis-related cognitive impairment.

[Validation of the Montreal Cognitive Assessment (MoCA) as a screening tool for mild cognitive impairment in the population of Buenos Aires, Argentina]. / Validez de la prueba de Evaluación Cognitiva de Montreal (MoCA) como una herramienta de screening para detectar Deterioro Cognitivo Leve en población de Buenos Aires, Argentina.

INTRODUCTION: The Montreal Cognitive Assessment (MoCA) test is a brief tool for neuropsychological assessment. OBJECTIVE: to validate the MoCAin the population of Buenos Aires, Argentina, to allow for the use of the test for the detection of Mild Cognitive Impairment (MCI). METHODS: The sample consisted of 269 adults over 60 years old and of schooling of more than 6 years (healthy adults n = 115 and MCIn = 154). Receiver operating characteristic (ROC) analysis was used to establish the relationship between the diagnoses of the patients and the scores obtained at MoCA. The optimal cut-off points were selected, and the positive and negative predictive value were calculated for them. RESULTS: The area under the curve (AUC) was 0,741 (p <0001, 95% CI:.682 -.800) for the MMSE and 0.810 (p <0001, 95% CI:.759 -. 861) for the MoCA test. The cut point suggested using the MoCA test is 26 points, which throws .727 of sensitivity and a specificity of. 748. CONCLUSION: The MoCA test is a useful test for clinical consultation. Its brevity and simplicity place it as an interesting instrument for neuropsychological screening in the Argentinian population.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile.

METHODS: This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. RESULTS: Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). DISCUSSION: In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile / Utilidad del tensor de difusión en esclerosis lateral amiotrofica: potencial biomarcador y asociación con el perfil cognitivo

ABSTRACT The objective of this preliminary study was to correlate diffusion tensor imaging (DTI) alterations with the cognitive profile of patients with amyotrophic lateral sclerosis (ALS). Methods This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. Results Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). Discussion In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

RESUMEN El objetivo del presente estudio preliminar fue correlacionar alteraciones del Tensor de Difusión (TD) con el perfil cognitivo de pacientes con Esclerosis Lateral Amiotrofica (ELA). Metodos Se realizó estudio casos-controles entre el 1 de Diciembre del 2012 hasta el 1 de Diciembre del 2014. Se registraron datos clínicos y demográficos. Se utilizó batería de tests neuropsicológicos adaptada a ELA. Se realizó RMN de cerebro con TD en todos los pacientes, la Fracción de Anisotropía (FA) se analizó en sustancia blanca, utilizando el programa Tract Based Spatial Statistics. Resultados Se incluyeron 24 pacientes con ELA (15 mujeres, edad media 66.9 + -2.3) y 13 controles sanos (4 mujeres, edad media 66.9 +-2). El TD mostró daño en sustancia blanca en los pacientes con ELA vs controles (p < 0.001). Discusión En nuestro estudio preliminar las alteraciones de sustancia blanca en TD se asociaron significativamente con alteraciones cognitivas en pacientes con ELA.

[Treatment with vitamin D and slowing of progression to severe stage of Alzheimer's disease]. / Tratamiento con vitamina D y enlentecimiento de la progresión a estadio severo en enfermedad de Alzheimer.

The aim of the study was to analyze the impact of treatment with vitamin D in the progression of Alzheimer's disease. We performed a retrospective study including patients with mild stage of Alzheimer's disease with more than four years of follow-up. The presence of cardiovascular risk factors, osteoporosis, treatment with memantine, acetylcholinesterase inhibitors drugs and vitamin D were analyzed as independent variables. Time of progression to moderate and severe Alzheimer's disease was analyzed as dependent variable. The analysis was done using multivariate linear regression model, Kaplan Meier analysis, Chi-square and T test. Two hundred and two patients met the inclusion criteria. 11% of the patients (n = 23) remained in the mild stage of the disease, 54% (n = 110) developed the moderate form in a mean time of 3 ± 1.4 years while 35% (n = 69) developed the severe form in a mean time of 4.6 ± 1.4 years. Time of progression to severe stage of Alzheimer's disease was slower in patients under treatment with vitamin D compared with those without treatment (5.4 ± 0.4 years vs. 4.4 ± 0.16 years respectively, p=0.003). Treatment with vitamin D may be an independent protecting factor in the progression of Alzheimer's disease.

Cardiovascular risk factors and frontotemporal dementia: a case-control study.

Cardiovascular risk factors (CRF) were widely described as related to dementia. There are very few studies regarding this association in FTD. The objective of the study was to compare the frequency of CRF in our population with FTD and controls. 100 consecutive subjects with FTD diagnosis according to Lund-Manchester clinical criteria and 200 controls matched by age and sex were included between January 2003 to February 2007 at the Cognitive and Behavior Unit of Hospital Italiano de Buenos Aires. Clinical evaluation, laboratory tests, brain images (CT/MRI), neuropsychological and neuropsychiatric assessment were performed. Multiple regression analysis was performed to analyze the association in CRF between FTD patients vs. controls. The mean age in FTD was 69.7 ± 0.9 vs. 70.1 ± 0.8 in controls (p 0.12). No difference in gender was observed between cases and controls. No differences were identified between patients and controls regarding hypertension (HTA) (65% vs. 67,3% p 0.44); dyslipidemia (57% vs. 54.7% p 0.74); obesity (39% vs. 27.6% p 0.14) and hypothyroidism (26% vs. 17.1% p 0.1). A significant difference was observed for Diabetes Mellitus (39% vs. 22.6% p 0.001). In our population, Diabetes Mellitus was associated as an independent risk factor for FTD. To our knowledge this is the first report in which CRF were evaluated prospectively in FTD patients. More studies are needed to confirm this finding in larger populations.

Tratamiento con vitamina D y enlentecimiento de la progresión a estadio severo en enfermedad de Alzheimer / [Treatment with vitamin D and slowing of progression to severe stage of Alzheimer’s disease].

The aim of the study was to analyze the impact of treatment with vitamin D in the progression of Alzheimer’s disease. We performed a retrospective study including patients with mild stage of Alzheimer’s disease with more than four years of follow-up. The presence of cardiovascular risk factors, osteoporosis, treatment with memantine, acetylcholinesterase inhibitors drugs and vitamin D were analyzed as independent variables. Time of progression to moderate and severe Alzheimer’s disease was analyzed as dependent variable. The analysis was done using multivariate linear regression model, Kaplan Meier analysis, Chi-square and T test. Two hundred and two patients met the inclusion criteria. 11

of the patients (n = 23) remained in the mild stage of the disease, 54

(n = 110) developed the moderate form in a mean time of 3 ± 1.4 years while 35

(n = 69) developed the severe form in a mean time of 4.6 ± 1.4 years. Time of progression to severe stage of Alzheimer’s disease was slower in patients under treatment with vitamin D compared with those without treatment (5.4 ± 0.4 years vs. 4.4 ± 0.16 years respectively, p=0.003). Treatment with vitamin D may be an independent protecting factor in the progression of Alzheimer’s disease.

Tratamiento con vitamina D y enlentecimiento de la progresión a estadio severo en enfermedad de Alzheimer. / [Treatment with vitamin D and slowing of progression to severe stage of Alzheimers disease].

The aim of the study was to analyze the impact of treatment with vitamin D in the progression of Alzheimers disease. We performed a retrospective study including patients with mild stage of Alzheimers disease with more than four years of follow-up. The presence of cardiovascular risk factors, osteoporosis, treatment with memantine, acetylcholinesterase inhibitors drugs and vitamin D were analyzed as independent variables. Time of progression to moderate and severe Alzheimers disease was analyzed as dependent variable. The analysis was done using multivariate linear regression model, Kaplan Meier analysis, Chi-square and T test. Two hundred and two patients met the inclusion criteria. 11

of the patients (n = 23) remained in the mild stage of the disease, 54

(n = 110) developed the moderate form in a mean time of 3 ± 1.4 years while 35

(n = 69) developed the severe form in a mean time of 4.6 ± 1.4 years. Time of progression to severe stage of Alzheimers disease was slower in patients under treatment with vitamin D compared with those without treatment (5.4 ± 0.4 years vs. 4.4 ± 0.16 years respectively, p=0.003). Treatment with vitamin D may be an independent protecting factor in the progression of Alzheimers disease.