Alzheimer`s disease diagnosis disclosure in Brazil: a survey of specialized physicians` current practice and attitudes

Background: There is little, though growing, interest in the research area of attitudes held among physicians towards disclosing the diagnosis of dementia and Alzheimer`s disease (AD), or the current practice on AD disclosure. This study aimed to investigate the practice and attitudes of specialized physicians towards AD diagnosis disclosure in Brazil. Methods: A questionnaire was devised to survey the current practice and attitudes regarding diagnosis disclosure of AD in Brazil and sent to specialized physicians (170 geriatricians, 300 neurologists and 500 psychiatrists) by electronic mail. Results: From 970 potential respondents, 181 physicians who usually attend AD patients returned the questionnaire. There were no significant differences between the three specialties regarding the frequency with which they informed patients of their AD diagnosis (p = 0.17). The results revealed that only 44.8% of the physicians would regularly inform the patient of the diagnosis, although 85.6% of these use clear terminology. Despite their usual practice, 76.8% would want to know their diagnosis if they themselves were affected by AD. Conclusions: Disclosure of AD diagnosis is not common among specialized physicians in Brazil and different factors are involved. In the clinical context, discussion on advantages of diagnosis disclosure can be useful for improving the care of AD patients and their families.

Glutamate(NMDA) receptor NR1 subunit mRNA expression in Alzheimer's disease

We analyzed the expression profile of two NMDAR1 mRNA isoform subsets. NR1(0xx) and NR1(1xx), in discrete regions of human cerebral cortex. The subsets are characterized by the absence or presence of a 21-amino acid N-terminal cassette. Reverse transcription polymerase chain reaction for NR1 isoforms was performed on total RNA preparations from spared and susceptible regions from 10 pathologically confirmed Alzheimer's disease (AD) cases and 10 matched controls. Primers spanning the splice insert yielded two bands, 342 bp (NR1(0xx)) and 405 bp (NR1(1xx)), on agarose gel electrophoresis. The bands were visualized with ethidium and quantified by densitometry. NR1(1xx) transcript expression was calculated as a proportion of the NR1(1xx) + NR1(0xx) total. Values were significantly lower in AD cases than in controls in mid-cingulate cortex, p < 0.01, superior temporal cortex, p < 0.01 and hippocampus, p similar to 0.05. Cortical proportionate NR1(1xx) transcript expression was invariant over the range of ages acid areas of controls tested, at similar to 50%. This was also true for AD motor and occipital cortex. Proportionate NR1(1xx) expression in AD cingulate and temporal cortex was lower at younger ages and increased with age: this regression was significantly different from that in the homotropic areas of controls. Variations in NR1 N-terminal cassette expression may underlie the local vulnerability to excitotoxic damage of some areas in the AD brain. Alternatively, changes in NR1 mRNA expression may arise as a consequence of the AD disease process.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy): an Australian perspective

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is a recently described cause of stroke or stroke-like episodes. It is caused by mutations in the Notch3 gene on chromosome 19p. We sought to demonstrate mutations of the Notch3 gene in Australian patients suspected of having CADASIL. Patients from several families were referred to the study. A diagnosis was determined clinically and by neuroimaging. Those suspected of having CADASIL had sequencing of exons 3 and 4 of the Notch3 gene. Eight patients, two of whom were siblings, were suspected of having CADASIL. Five patients (including the siblings) had mutations. Because of strong clustering of Notch3 mutations in CADASIL, this has potential as a reliable test for the disease in Australian patients. (C) 2001 Harcourt Publishers Ltd.

A segmentation-based and partial-volume-compensated method for an accurate measurement of lateral ventricular volumes on T-1-weighted magnetic resonance images

Lateral ventricular volumes based on segmented brain MR images can be significantly underestimated if partial volume effects are not considered. This is because a group of voxels in the neighborhood of lateral ventricles is often mis-classified as gray matter voxels due to partial volume effects. This group of voxels is actually a mixture of ventricular cerebro-spinal fluid and the white matter and therefore, a portion of it should be included as part of the lateral ventricular structure. In this note, we describe an automated method for the measurement of lateral ventricular volumes on segmented brain MR images. Image segmentation was carried in combination of intensity correction and thresholding. The method is featured with a procedure for addressing mis-classified voxels in the surrounding of lateral ventricles. A detailed analysis showed that lateral ventricular volumes could be underestimated by 10 to 30% depending upon the size of the lateral ventricular structure, if mis-classified voxels were not included. Validation of the method was done through comparison with the averaged manually traced volumes. Finally, the merit of the method is demonstrated in the evaluation of the rate of lateral ventricular enlargement. (C) 2001 Elsevier Science Inc. All rights reserved.

Complex language functions and subcortical mechanisms: evidence from Huntington's disease and patients with non-thalamic subcortical lesions

The neuropathological changes associated with Huntington's disease (HD) are most marked in the head of the caudate nucleus and, to a lesser extent, in the putamen and globus pallidus, suggesting that at least part of the language impairments found in patients with HD may result from non-thalamic subcortical (NTS) pathology. The present study aimed to test the hypothesis that a signature profile of impaired language functions is found in patients who have sustained damage to the non-thalamic subcortex, either focally induced or resulting from neurodegenerative pathology. The language abilities of a group of patients with Huntington's disease (n=13) were compared with those of an age- and education-matched group of patients with chronic NTS lesions following stroke (n=13) and a non-neurologically impaired control group (n=13). The three groups were compared on language tasks that assessed both primary and more complex language abilities. The primary language battery consisted of The Western Aphasia Battery and The Boston Naming Test, whilst the more complex cognitive-linguistic battery employed selected subtests from The Test of Language Competence-Expanded, The Test of Word Knowledge and The Word Test-Revised. On many of the tests of primary language function from the Western Aphasia Battery, both the HD and NTS participants performed in a similar manner to the control participants. The language performances of the HD participants were significantly more impaired (p&lt;0.05 using modified Bonferroni adjustments) than the control group, however, on various lexico-semantic tasks (e. g. the Boston Naming Test and providing definitions), on both single-word and sentence-level generative tasks (e. g. category fluency and formulating sentences), and on tasks which required interpretation of ambiguous, figurative and inferential meaning. The difficulties that patients with HD experienced with tasks assessing complex language abilities were strikingly similar, both qualitatively and quantitatively, to the language profile produced by NTS participants. The results provide evidence to suggest that a signature language profile is associated with damage to the non-thalamic subcortex resulting from either focal neurological insult or a degenerative disease.

Spermine modulation of the glutamate(NMDA) receptor is differentially responsive to conantokins in normal and Alzheimer's disease human cerebral cortex

The pharmacology of the N -methyl-d-aspartate (NMDA) receptor site was examined in pathologically affected and relatively spared regions of cerebral cortex tissue obtained at autopsy from Alzheimer's disease cases and matched controls. The affinity and density of the [H-3]MK-801 binding site were delineated along with the enhancement of [H-3]MK-801 binding by glutamate and spermine. Maximal enhancement induced by either ligand was regionally variable; glutamate-mediated maximal enhancement was higher in controls than in Alzheimer's cases in pathologically spared regions, whereas spermine-mediated maximal enhancement was higher in controls in areas susceptible to pathological damage. These and other data suggest that the subunit composition of NMDA receptors may be locally variable. Studies with modified conantokin-G (con-G) peptides showed that Ala(7)-con-G had higher affinity than Lys(7)-con-G, and also defined two distinct binding sites in controls. Nevertheless, the affinity for Lys(7)-con-G was higher overall in Alzheimer's brain than in control brain, whereas the reverse was true for Ala(7)-con-G. Over-excitation mediated by specific NMDA receptors might contribute to localized brain damage in Alzheimer's disease. Modified conantokins are useful for identifying the NMDA receptors involved, and may have potential as protective agents.

Behaviour of older people admitted for residential respite care

The aim of this pilot study was to determine whether residential respite care is used because of disruptive behaviour displayed by older people. The specific objectives were to 1) characterise older people being admitted for residential respite care, 2) obtain a preliminary estimate of the proportion of older people in residential respite care because of disruptive behaviour, and, 3) examine the relationship between residential respite care and disruptive behaviour. A quantitative approach using a cross-sectional survey was employed. The respite recipients were 35 older people with a mean age of 81.5 years (range 67-96 years). The respite recipients had been admitted for residential respite care to aged care hostels and nursing homes in a provincial city and its surrounding rural area. Nurses rated disruptive behaviour using the Dementia Behavior Disturbance Scale (DBDS). Additional reliability data for the DBDS are provided. The study found that the largest specific group of residential respite care users were widows (31.4%) who lived alone in their own home. The reason for over half (51.4%) of the residential respite admissions was to give a carer a 'break' from the older person. Although a large proportion (80%) of respite recipients were rated as having disruptive behaviour, the proportion of admissions because of disruptive behaviour was much less (28.6%). People with dementia (37.1%) scored significantly higher than people without dementia on the DBDS [F (1,33)=15.57, p

A role for the dominant thalamus in language? A linguistic comparison of two cases subsequent to unilateral thalamotomy procedures in the dominant and non-dominant hemispheres

Background: Thalamotomy has been reported to be successful in ameliorating the motor symptoms of tremor and/or rigidity in people with Parkinson's disease (PD), emphasising the bona fide contribution of this subcortical nucleus to the neural circuitry subserving motor function. Despite evidence of parallel yet segregated associative and motor cortico-subcortical-cortical circuits, comparatively few studies have investigated the effects of this procedure on cognitive functions. In particular, research pertaining to the impact of thalamotomy on linguistic processes is fundamentally lacking. Aims: The purpose of this research was to investigate the effects of thalamotomy in the language dominant and non-dominant hemispheres on linguistic functioning, relative to operative theoretical models of subcortical participation in language. This paper compares the linguistic profiles of two males with PD, aged 75 years (10 years of formal education) and 62 years (22 years of formal education), subsequent to unilateral thalamotomy procedures within the language dominant and non-dominant hemispheres, respectively. Methods & Procedures: Comprehensive linguistic profiles comprising general and high-level linguistic abilities in addition to on-line semantic processing skills were compiled up to 1 month prior to surgery and 3 months post-operatively, within perceived on'' periods (i.e., when optimally medicated). Pre- and post-operative language performances were compared within-subjects to a group of 16 non-surgical Parkinson's controls (NSPD) and a group of 16 non-neurologically impaired adults (NC). Outcomes & Results: The findings of this research suggest a laterality effect with regard to the contribution of the thalamus to high-level linguistic abilities and, potentially, the temporal processing of semantic information. This outcome supports the application of high-level linguistic assessments and measures of semantic processing proficiency to the clinical management of individuals with dominant thalamic lesions. Conclusions: The results reported lend support to contemporary theories of dominant thalamic participation in language, serving to further elucidate our current understanding of the role of subcortical structures in mediating linguistic processes, relevant to cortical hemispheric dominance.

MR image-based measurement of rates of change in volumes of brain structures. Part II: Application to a study of Alzheimer's disease and normal aging

We present global and regional rates of brain atrophy measured on serially acquired T1-weighted brain MR images for a group of Alzheimer's disease (AD) patients and age-matched normal control (NC) subjects using the analysis procedure described in Part I. Three rates of brain atrophy: the rate of atrophy in the cerebrum, the rate of lateral ventricular enlargement and the rate of atrophy in the region of temporal lobes, were evaluated for 14 AD patients and 14 age-matched NC subjects. All three rates showed significant differences between the two groups, However, the greatest separation of the two groups was obtained when the regional rates were combined. This application has demonstrated that rates of brain atrophy, especially in specific regions of the brain, based on MR images can provide sensitive measures for evaluating the progression of AD. These measures will be useful for the evaluation of therapeutic effects of novel therapies for AD. (C) 2002 Elsevier Science Inc. All rights reserved.

Synaptic vesicle transport and synaptic membrane transporter sites in excitatory amino acid nerve terminals in Alzheimer disease

The apparent L-[H-3]glutamate uptake rate (v') was measured in synaptic vesicles isolated from cerebral cortex synaptosomes prepared from autopsied Alzheimer and non-Alzheimer dementia cases, and age-matched controls. The initial synaptosome preparations exhibited similar densities of D-[H-3]aspartate membrane binding sites (B-MAX values) in the three groups. In control brain the temporal cortex D-[H-3]aspartate B-MAX was 132% of that in motor cortex, parallel with the L- [H-3]glutamate v' values (temporal = 139% of motor; NS). Unlike D- [H-3]aspartate B-MAX values, L- [H-3]glutamate v' values were markedly and selectively lower in Alzheimer brain preparations than in controls, particularly in temporal cortex. The difference could not be attributed to differential effects of autopsy interval or age at death. Non-Alzheimer dementia cases resembled controls. The selective loss of vesicular glutamate transport is consistent with a dysfunction in the recycling of transmitter glutamate.

Dynamics of Gray Matter Loss in Alzheimer's Disease

We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer's disease (AD). The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices. The shifting deficits were asymmetric (left hemisphere >right hemisphere) and correlated with progressively declining cognitive status ( p 15% loss). The maps distinguished different phases of AD and differentiated AD from normal aging. Local gray matter loss rates (5.3 +/- 2.3% per year in AD v 0.9 +/- 0.9% per year in controls) were faster in the left hemisphere ( p < 0.029) than the right. Transient barriers to disease progression appeared at limbic/frontal boundaries. This degenerative sequence, observed in vivo as it developed, provides the first quantitative, dynamic visualization of cortical atrophic rates in normal elderly populations and in those with dementia.

Synthesis of optimization of [11C] Pittsburgh compound B by the captive solvent method

Mestrado em Medicina Nuclear.

Mental health and psychiatry research in Brazil: scientific production from 1999 to 2003

OBJECTIVE: To assess the extent of mental health scientific production in Brazil from 1999 to 2003, and to identify the nature of the publications generated, their sources of finance and the ways of publicly disseminating the research findings. METHODS: Searches for publications were conducted in the Medline and PsychInfo databases for the period 1999-2003. A semi-structured questionnaire developed by an international team was applied to 626 mental health researchers, covering each interviewee's educational background, research experience, access to funding sources, public impact and research priorities. The sample was composed by 626 mental health researchers identified from 792 publications indexed on Medline and PsychInfo databases for the period above, and from a list of reviewers of Revista Brasileira de Psiquiatria. RESULTS: In Brazil, 792 publications were produced by 525 authors between 1999 and 2003 (441 indexed in Medline and 398 in the ISI database). The main topics were: depression (29.1%), substance misuse (14.6%), psychoses (10%), childhood disorders (7%) and dementia (6.7%). Among the 626 Brazilian mental health researchers, 329 answered the questionnaire. CONCLUSIONS: There were steadily increasing numbers of Brazilian articles on mental health published in foreign journals from 1999 to 2003: the number of articles in Medline tripled and it doubled in the ISI database. The content of these articles corresponded to the priorities within mental health, but there is a need for better interlinking between researchers and mental health policymakers.

Assessment of the quality of brain regions and neuroimaging metrics as biomarkers of Alzheimer���s disease

Alzheimer Disease (AD) is characterized by progressive cognitive decline and dementia. Earlier diagnosis and classification of different stages of the disease are currently the main challenges and can be assessed by neuroimaging. With this work we aim to evaluate the quality of brain regions and neuroimaging metrics as biomarkers of AD. Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox functionalities were used to study AD by T1weighted, Diffusion Tensor Imaging and 18FAV45 PET, with data obtained from the AD Neuroimaging Initiative database, specifically 12 healthy controls (CTRL) and 33 patients with early mild cognitive impairment (EMCI), late MCI (LMCI) and AD (11 patients/group). The metrics evaluated were gray-matter volume (GMV), cortical thickness (CThk), mean diffusivity (MD), fractional anisotropy (FA), fiber count (FiberConn), node degree (Deg), cluster coefficient (ClusC) and relative standard-uptake-values (rSUV). Receiver Operating Characteristic (ROC) curves were used to evaluate and compare the diagnostic accuracy of the most significant metrics and brain regions and expressed as area under the curve (AUC). Comparisons were performed between groups. The RH-Accumbens/Deg demonstrated the highest AUC when differentiating between CTRLEMCI (82%), whether rSUV presented it in several brain regions when distinguishing CTRL-LMCI (99%). Regarding CTRL-AD, highest AUC were found with LH-STG/FiberConn and RH-FP/FiberConn (~100%). A larger number of neuroimaging metrics related with cortical atrophy with AUC>70% was found in CTRL-AD in both hemispheres, while in earlier stages, cortical metrics showed in more confined areas of the temporal region and mainly in LH, indicating an increasing of the spread of cortical atrophy that is characteristic of disease progression. In CTRL-EMCI several brain regions and neuroimaging metrics presented AUC>70% with a worst result in later stages suggesting these indicators as biomarkers for an earlier stage of MCI, although further research is necessary.

Altera����es da subst��ncia branca cerebral relacionadas com o envelhecimento

INTRODU����O: Estudos pr��vios, com t��cnicas de imagem, documentam de forma consistente a exist��ncia de altera����es da subst��ncia branca cerebral relacionadas com o envelhecimento (ASBRE). Tais altera����es poder��o ter um papel importante no decl��nio funcional do idoso, reflectindo���se sobretudo no desempenho motor e cognitivo, com repercuss��o evidente na pr��tica cl��nica. Apesar disso, a caracteriza����o em definitivo dos fen��tipos cl��nicos e da evolu����o das ASBRE continua por esclarecer, possivelmente pelas dificuldades metodol��gicas de que se reveste o seu estudo, incluindo: a adequa����o das baterias neuropsicol��gicas, a utiliza����o de amostras de doentes com diferentes graus de severidade e de envolvimento regional, as limita����es das diferentes escalas e a sensibilidade dos diferentes m��todos de imagem. A Resson��ncia Magn��tica (RM) de difus��o tem revelado grande sensibilidade para as altera����es isqu��micas, admitindo���se que poder�� permitir uma melhor caracteriza����o das ASBRE e deste modo possibilitar uma correla����o mais precisa com as vari��veis cognitivas e motoras, permitindo avaliar ainda a subst��ncia branca aparentemente normal (SBAN). OBJECTIVOS: Descrever a evolu����o imagiol��gica das ASBRE no intervalo de um ano e analisar a sua express��o cl��nica e impacto funcional; identificar factores preditivos de progress��o das ASBRE e de decl��nio funcional associado. Descrever a express��o cl��nica e perfil evolutivo dos doentes com ASBRE com envolvimento preferencial da regi��o parieto���occipital; comparar este grupo de doentes com os doentes com ASBRE, sem envolvimento preferencial desta regi��o. Medir os coeficientes de difus��o aparente (CDA), utilizando regi��es de interesse (RDI), em diferentes localiza����es da subst��ncia branca, incluindo subst��ncia branca lesada e SBAN, descrever sua evolu����o temporal no intervalo de um ano e determinar suas correla����es cl��nicas e imagiol��gicas. M��TODOS: Utilizando uma amostra de conveni��ncia, foram estudados 30 doentes, com mais de 65 anos, sem incapacidade funcional ou com incapacidade m��nima, avaliada pela escala de actividades instrumentais da vida di��ria (IADL), apresentando ASBRE em TC. Foi utilizado um protocolo exaustivo de avalia����o cl��nica (com particular destaque para as fun����es motoras e cognitivas) e imagiol��gica, em dois momentos de avalia����o separados por um ano de intervalo (t0 e t1). As ASBRE foram avaliadas com escalas visuais, escala ARWMC e escala de Fazekas, e os doentes foram estudados em fun����o do grau de severidade (ligeiro versus moderado a grave na escala de Fazekas) e de um envolvimento preferencial posterior (definido como 2 ou mais pontos na escala ARWMC na regi��o parieto���occipital por compara����o com a regi��o frontal). Os CDA foram avaliados mediante estudo de RDI, na subst��ncia branca frontal lesada (SBFL) e SBAN frontal, parieto���occipital e dos ped��nculos cerebelosos. Para verificar diferen��as na ordem de distribui����o das vari��veis foi usado o teste de Mann���Whitney e para compara����o de propor����es, o teste exacto de Fisher. Na compara����o entre a avalia����o em t0 e t1 foi usado o teste Wilcoxon Signed Ranks na compara����o da distribui����o da ordem das vari��veis e o teste McNemar na an��lise de frequ��ncias. Na an��lise correlacional foram utilizados os testes de T para vari��veis emparelhadas e as correla����es entre estas foram efectuadas com o coeficiente de correla����o de Spearman ou de Pearson. O trabalho foi aprovado pela Comiss��o de ��tica do hospital onde foi realizado e todos os doentes inclu��dos assinaram um consentimento informado. RESULTADOS: A idade m��dia da popula����o estudada foi 72,5 anos (17 doentes eram do sexo masculino). No final de um ano, 1 doente tinha falecido e 3 doentes n��o completaram a avalia����o imagiol��gica. Registou���se uma progress��o significativa das ASBRE segundo a escala ARWMC (t0: 8,37 / t1: 9,65 ; p<0,001). Na an��lise funcional, motora e cognitiva, n��o houve um agravamento significativo. Avaliando os doentes em t0 e t1 segundo o grau de severidade das ASBRE, o grupo com atingimento moderado a grave (ASBRE2) comparado com o grupo com atingimento ligeiro (ASBRE1) apresentava: maior extens��o de les��o da subst��ncia branca (ARWMC t0: 11,9 / 4,8 ; p<0.001 ; t1: 14,0 / 5,9 ; p<0,001); tend��ncia a pior desempenho funcional (IADL t0: 90,7 / 99,2 ; p=0,023; t1: 86,4 / 96,7 ; p=n.s.) e motor (SPPB t0: 9,8 / 10,3 ; p=n.s. ; t1: 9,5 / 10,5 ; p=0,058); tend��ncia a maior compromisso do humor (Escala Cornell t0: 6,7 / 3,5 ; p=0,037; t1: 6,2 / 4,5 ; p=n.s.). Analisando a evolu����o, de t0 para t1, de cada um dos grupos (ASBRE2 e ASBRE1) registou���se: aumento da extens��o da les��o da subst��ncia branca em ambos (ASBRE2: 12,0 / 14,0;z=���2,687 ; p=0,007; ASBR1: 4,8 / 5,9 ; z=���2,724 ; p=0,006); varia����o n��o significativa funcional e motora; tend��ncia ao agravamento em ambos na prova de Cancelamento de d��gitos (ASBRE2: 17,5 / 17,4 ; p=n.s. ; ASBRE1: 19,9 / 16,9 ; z=���2,096 ; p=0,036);tend��ncia �� melhoria em ambos no MMS (ASBRE2: 25,7 / 27,5 ; z=���2,155 ; p=0,031; ASBRE1: 27,5 / 28,2 ; p=n.s). Avaliando os doentes em t0 e t1 em fun����o do padr��o de distribui����o das ASBRE, os doentes com um envolvimento preferencial posterior (ASBREP) comparados com os restantes (ASBREnP), apresentavam: maior extens��o da les��o (ARWMC t0: 10,8 / 6,9 ; p=0,025; t1: 12,9 / 7,6 ; p=0,011); diferen��as n��o significativas no desempenho motor; tend��ncia a melhor desempenho na prova dos Labirintos (t0: 8,1 / 11,8 ; p=0,06; t1: 8,7 / 9,5 ; p=n.s.) e Cancelamento de d��gitos (t0: 20,9 / 17,4 ; p=0,045; t1: 18,5 / 16,3 ; p=n.s.); tend��ncia a maior compromisso depressivo na GDS (t0: 5,0 / 3,68 ; p=n.s. ; t1: 5,7 / 3,3 p=0,033). Analisando o perfil evolutivo de t0 para t1, registou���se: aumento da extens��o da les��o nos dois grupos (ASBREP: 10,8 / 12,9 ; z=���2,555 ; P=0,011; ASBREnP: 6,4 / 7,6 ; z=���2,877 ; p=0,04); varia����o em sentidos diferentes com melhoria funcional no grupo ASBREP (91,0 / 95,5 ; z=���0,926 ; p=0,036) e agravamento no grupo ASBREnP (96,7 / 89,8 ; z=���2,032 ; p=0,042); varia����o sem sentidos diferentes, com agravamento significativo no grupo ASBREnP no item esta����o de p�� do SPPB (ASBREP 3,8/3,9 p=n.s.; ASBREnP 3,9/3,6; z=���2,236 ; p=0,025); tend��ncia �� melhoria nos dois grupos no MMS (ASBREP: 27,2 / 28,2 ; p=n.s.; ASBREnP: 26,3 / 27,7 ; z=���2,413 ; p=0,016) e tend��ncia em sentidos diferentes no Trail Making, com eventual melhoria no grupo ASBREP (113,9 / 91,6 ; p=n.s.) e agravamento no grupo ASBREnP (113,7 / 152,0 ; z=���2,155 ; p=0,031). Na an��lise da imagem, utilizando a escala ARWMC e o estudo dos CDA, na avalia����o transversal na inclus��o, a compara����o entre as pontua����es m��dias da escala ARWML nas diferentes regi��es mostrava diferen��as significativas (F=39,54 , p<0,0001). A an��lise comparativa post���hoc de Bonferroni mostrou valores significativamente mais altos para as regi��es frontais e parieto���occipitais (p<0,0001). Os valores m��dios dos CDA eram significativamente diferentes entre regi��es (F=44,56; p<0,0001), sendo mais altos na SBFL (p<0,0001). N��o existia diferen��a significativa entre os valores registados na SBAN nas regi��es frontais e parieto���occipitais. As pontua����es regionais da escala ARWMC e os valores m��dios dos CDA correlacionavam���se todos de forma positiva. A pontua����o da escala ARWMC na regi��o frontal correlacionava���se significativamente com os valores do CDA da SBFL (r=0,467 ; p=0,012). Existia tend��ncia para uma correla����o positiva entre as pontua����es da escala ARWMC na regi��o frontal e os valores m��dios dos CDA na SBAN frontal (r=0,276 ; p=0,155). As pontua����es da escala ARWMC e os CDA correlacionavam���se de forma positiva com a idade e com a tens��o arterial (TA). Foram encontradas correla����es significativas entre: idade e SBAN frontal (r=0,440 ; p=0,019); TA diast��lica e SBFL (r=0,386 ; p=0,034); TA sist��lica e SBAN Parieto���occipital (r=0,407 ; P=0,032). Na avalia����o motora e cognitiva, dado elevado n��mero de vari��veis, foi efectuada uma an��lise de factor principal. Registou���se uma tend��ncia global negativa na correla����o entre as pontua����es da escala visual na regi��o frontal, os valores dos CDA, e o desempenho motor e cognitivo. Na an��lise evolutiva, (n=19), registou���se varia����o significativa dos CDA, com aumento na SBFL (Direita: z=���2,875 ; p=0,004 ; Esquerda: z=���2,113 ; p=0,035) e diminui����o na SBAN dos ped��nculos cerebelosos (Direita: z=���2,094 ; p=0,036 ; Esquerda: z=���1,989 ; p=0,047). Foi observada uma correla����o negativa entre a varia����o do CDA na SBAN dos ped��nculos cerebelosos e na SBFL contralateral (SBAN ped��nculo cerebeloso Esquerdo / SBFL Direita: r=���0,133 ; p=n.s.; SBAN ped��nculo cerebeloso Direito / SBFL Esquerda: r=���0,561 ; p=0,012). Os valores dos CDA �� direita correlacionavam���se de forma positiva com a velocidade da marcha (r=0,562 ; p=0,012). CONCLUS��ES: A progress��o das ASBRE pode ser observada com uma escala visual detalhada no intervalo de um ano. Contudo, o eventual agravamento da incapacidade funcional, motora e cognitiva, n��o parece ser apreci��vel em igual intervalo de tempo. A maior severidade das ASBRE associa���se a uma tend��ncia para um maior compromisso funcional, motor e possivelmente do humor. A quest��o da progress��o em escalas simplificadas, de um est��dio ligeiro para um est��dio moderado a grave, n��o �� elucidada pelos resultados do presente trabalho. Os doentes com um envolvimento preferencial da regi��o parieto���occipital poder��o constituir um subgrupo distinto que, apesar de ter maior extens��o de les��o, parece ter um melhor desempenho motor e cognitivo. O perfil evolutivo destes doentes parece igualmente ser distinto, n��o se observando a tend��ncia ao agravamento funcional, motor e cognitivo (sobretudo em provas de fun����o executiva) que se encontra nos restantes doentes. A an��lise transversal na inclus��o, utilizando uma escala visual e o estudo dos CDA, sugere que a severidade das ASBRE se correlaciona com o compromisso motor e cognitivo, bem como com a idade e com a TA. Uma maior vulnerabilidade da subst��ncia branca frontal �� les��o vascular parece ter um papel importante no compromisso motor e na disfun����o executiva, (essencialmente �� custa do compromisso da aten����o), possivelmente associada �� desconex��o dos circuitos fronto���subcorticais. A an��lise dos CDA sugere que isso �� v��lido igualmente para a SBAN e sublinha que, as imagens de RM convencional poder��o n��o traduzir a verdadeira extens��o da les��o e consequentemente do compromisso motor e cognitivo. A rela����o entre a progress��o da doen��a vascular em les��es frontais constitu��das e a redu����o do CDA no ped��nculo cerebeloso contralateral poder�� estar associada a um pior desempenho motor. A disrup����o dos circuitos fronto���cerebelosos, determinando hipometabolismo e diminui����o da perfus��o no cerebelo, poder�� ser respons��vel pela diminui����o do CDA no cerebelo. ABSTRACT INTRODUCTION: Previous studies, with new imaging techniques, have consistently documented the presence of age���related white matter lesions (ARWML), emphasizing their role in agerelated functional decline, mainly related to motor and cognitive impairment, and inherent consequences in clinical practice. However clinical significance of ARWML remains to be elucidated, probably on account of methodological difficulties such as: specific neuropsychological batteries, utilization of samples with different degrees of severity and regional involvement, utilization of different imaging scales and different sensitivity of imaging techniques. Recently, Diffusion Weighted Magnetic Ressonance imaging (DWI) has shown a higher sensitivity to ischemic lesions, suggesting it might be superior for characterization of ARWML, allowing more precise correlation with motor and cognitive variables, and evaluating also normal appearing white matter (NAWM). OBJECTIVES: To describe imagiologic evolution of ARWML within one year interval and to analyse its clinical and functional significance. To identify predictors of ARWML progression and associated functional impairment. To describe clinical characteristics and evolution profile of patients with predominantly posterior lesions; to compare this group of patients with patients without predominantly posterior lesions. To study average Apparent Diffusion Coeficcients (ADC) in different white matter regions using regions of interest (ROI); to analyse their evolution profile and to determine their clinical and imagiologic correlations. METHODS: A sample of 30 patients older than 65 years, without functional impairment or with minimal impairment, according to the Instrumental Activities of Daily Lliving scale, with ARWML on CT scan, were studied in a cross���sectional design. An extensive clinical(with detailed motor and cognitive evaluation) and imagiologic protocol was applied in two one���year interval separate moments (t0 and t1). ARWML were studied using visual scales, ARWMC and Fazekas���s scale, and patients were studied according to degree of severity (Fazekas scale mild versus moderate / severe) and preferential involvement of the posterior region (defined as 2 or more points in the ARWMC scale in the parietooccipital region compared with frontal region). Evaluation of ADC was performed using ROI in frontal lesioned white matter (FLWM) and NAWM (frontal, parieto���occipital and cerebellar regions). To study differences in the distribution of variables the Mann���Whitney test was used and to compare proportions the exact Fisher Test was used. To compare temporal evolution profile between t0 and t1, the Wilcoxon Signed ranks Test was used to analyse the distribution of variables and the Mc Nemar Test to analyse frequencies. Correlation analysis was performed using Spearman or Pearson tests. The study was approved by the local Ethics Committee and all patients signed an informed consent. RESULTS: Mean age was 72.5 years (17 patients were male). By the end of the study, one patient was dead and 3 patients did not undergo brain imaging. There was a higher extent of ARWML evaluated with the ARWMC scale (t0: 8.37 / t1: 9.65 ; p<0.001). Functional, motor and cognitive performance did not progress significantly. Evaluating patients in t0 and t1 according to the degree of severity (Fazekas scale), the moderate / severe group of patients (WML2), compared with the mild group (WML1), showed: higher extent of lesion (ARWMC scale t0: 11.9 / 4.8 ; p<0.001 ; t1: 14.0 / 5.9 ; p<0.001); tendency to worse functional (IADL t0: 90.7 / 99.2 ; p=0.023; t1: 86.4 / 96.7 ; p=n.s.) and motor (SPPB t0: 9.8 / 10.3 ; p=n.s. ; t1: 9.5 / 10.5 ; p=0.058) performance; tendency to higher depressive scores (Cornell Scale t0: 6.7 / 3.5 ; p=0.037; t1: 6.2 / 4.5; p=n.s.). Analysing the evolution profile from t0 to t1 of each group (WML2 and WML1), there was a higher extent of lesion (ARWMC scale) in both (WML2: 12.0 / 14.0; z=���2.687 ; p=0.007; WML1: 4.8 / 5.9 ; z=���2.724 ; p=0.006); non���significant variation in functional and motor performances; tendency to worse performance on the Digit Cancelling (WML2: 17.5 / 17.4 ; p=n.s. ; WML1: 19.9 / 16.9 ; z=���2.096 ; p=0,036) and to better performance on the MMS (WML2: 25.7 / 27.5 ; z=���2.155 ; p=0.031; WML1: 27.5/ 28.2 ; p=n.s). Evaluating patients in t0 and t1 according to the regional distribution of ARWML, patients with predominantly posterior lesions (WMLP) compared with the rest of the group (WMLnP), showed: higher extent of lesion (ARWMC scale t0: 10.8 / 6.9 ; p=0.025; t1:12.9 / 7.6 ; p=0.011); non significant differences on motor evaluation; tendency to a better performance on Maze (t0: 8.1 / 11.8 ; p=0.06; t1: 8.7 / 9.5 ; p=n.s.) and Digit cancelling (t0: 20.9 / 17.4 ; p=0.045; t1: 18.5 / 16.3 ; p=n.s.) tests;tendency to higher scores on GDS (t0: 5.0 / 3.68 ; p=n.s. ; t1: 5.7 / 3.3 p=0.033). Analysing the evolution profile from t0 to t1 of each group (WMLP and WMLnP), there was: higher extent of lesion (ARWMC scale) in both groups (WMLP: 10.8 / 12.9 ;z=���2,555 ; P=0,011; WMLnP: 6.4 / 7.6 ; z=���2.877; p=0.04); variation in different directions with better functional performance in the group WMLP (91.0 / 95.5 ;z=���0.926 ; p=0.036) and worse in WMLnP (96.7 / 89.8 ; z=���2.032 ; p=0.042); variation in different directions with worse motor performance in one SPPB item (total stands) in the group WMLnP (WMLP 3.8/3.9 p=n.s.; ASBREnP 3.9/3.6; z=���2.236 ; p=0.025);tendency to improvement in both groups in MMS (WMLP: 27.2 / 28.2 ; p=n.s.; WMLnP:26.3 / 27.7 ; z=���2.413 ; p=0.016); tendency to a variation in different directions in the Trail Making Test, with possible improvement in the group WMLP (113.9 / 91.6 ;p=n.s.) and worsening in the group WMLnP (113.7 / 152.0 ; z=���2.155 ; p=0.031). Imaging analysis in the inclusion, using the ARWMC scale and ADC evaluation, showed significant differences in different regions (F=39.54, p<0.0001). Comparative post���hoc Bonferroni analysis showed significantly higher scores in the frontal and parieto���occipital regions (p<0.0001. ADC values were significantly different between regions (F=44.56; p<0.0001), being higher in FLWM (p<0���0001). There was no significant difference between ADC in NAWM in frontal and parieto���occipital regions. ARWMC scores and ADC values correlated positively. Significant correlations were found between frontal ARWMC score and FLWM ADC values (r=0.467 ; p=0.012). ARWMC scores and ADC values correlated positively with age and blood pressure. Significant correlations were: age and frontal NAWM (r=0.440 ; p=0.019); Diastolic blood pressure and FLWM (r=0.386 ; p=0.034); sistolic blood pressure and parietooccipital NAWM (r=0.407 ; P=0.032). Due to the higher number of motor and cognitive variables a preliminary study was done, using principal component analysis. A global tendency to a negative correlation was found between ARWMC scores, ADC values and motor and cognitive performances. Evolutive analysis of ADC (n=19), showed a significant variation, with higher values in t1 in FLWM (Right: z=���2.875 ; p=0.004 ; Left: z=���2.113 ; p=0.035) and lower values in t1 in cerebellar NAWM (Right: z=���2.094 ; p=0.036 ; Left: z=���1.989 ; p=0.047). A negative correlation was found between ADC variation in cerebellar NAWM and contralateral FLWM (Left cerebellar NAWM / Right FLWM: r=���0.133 ; p=n.s.; Right cerebellar NAWM/ Left FLWM: r=���0.561 ; p=0.012). ADC values on the right correlated positively with walking speed (r=0,562 ; p=0,012). CONCLUSIONS: Progression of ARWML can be documented with a detailed visual scale in a one year interval. However, functional, motor and cognitive impairment, do not seem to progress significantly within the same period. A higher severity of ARWML is associated with a tendency to a worse functional and motor performance (and possibly to higher scores in depression scales). The issue of progression in a simplified visual scale from a mild to a moderate / severe degree of ARWML is not further elucidated. Patients with predominantly posterior lesions may be a subset of ARWML patients, with a different profile, that despite higher extent of lesion, seem to fair better than the rest of the group, namely with better performance on motor and cognitive tests. Evolution profile of this subset of patients also seems to be different, without a clearcut tendency to worsening functional, motor and cognitive (particularly for executive function tests) performance that is observed in the rest of the group. Imaging analysis, with a visual scale and ADC evaluation, suggests that severity of ARWML correlates negatively with cognitive and motor performance and positively with age and blood pressure. A higher vulnerability of frontal white matter to vascular disease seems to play an important role in motor and cognitive dysfunction, mainly determined by impairment of attention skills associated with frontal���subcortical disconnection. DWI results, suggest that this may also be true for NAWM, underlining that conventional MR images may not represent the true extent of cognitive decline. The relation between vascular disease progression inside frontal lesions and ADC reduction in contralateral cerebellar peduncles, may be associated with a worse motor performance. Disruption of fronto���cerebellar cicuits, with associated regional hypometabolism, may be responsible for the reduction of cerebellar ADC.