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BACKGROUND: Different pathogenetic pathways have been proposed for neuropsychiatric (NP) manifestations in systemic lupus erythematosus (SLE). OBJECTIVE: To describe the patient characteristics of a large cohort of patients with SLE with NP manifestations (NPSLE) in a single centre and to review whether these and other data are compatible with immune-mediated mechanisms. METHODS: A total of 212 patients were identified from MRI scans of the brain ordered for suspected NPSLE. Data were collected from the medical records. NP syndromes were classified according to the American College of Rheumatology (ACR) nomenclature and case definitions. RESULTS: 155 patients fulfilled the criteria for SLE. In 102 patients NP manifestations were attributed to SLE itself (primary NPSLE) whereas, in the remaining patients, the NP symptoms were due to other causes. The median age at the time of SLE diagnosis in patients with primary NPSLE was 27.5 years and the median duration prior to NPSLE was 2.8 years. Forty patients (39%) had a NP manifestation in the first year of the disease. Cerebrovascular disease, cognitive dysfunction, seizures and headache were the most prevalent syndromes. In 47% of patients with primary NPSLE the MRI scan of the brain showed no abnormalities. CONCLUSIONS: Most NP manifestations in SLE occur early in the disease. This finding, as well as data from quantitative imaging studies and recent pathological studies, point to an immune-mediated pathogenesis.
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Enfermedades del Sistema Inmune/complicaciones , Vasculitis por Lupus del Sistema Nervioso Central/etiología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Glucocorticoides/uso terapéutico , Humanos , Enfermedades del Sistema Inmune/diagnóstico , Enfermedades del Sistema Inmune/epidemiología , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/epidemiología , Imagen por Resonancia Magnética , Masculino , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: To evaluate ventricular shape differences along the complete surface of the lateral and third ventricles of persons with subjective memory complaints (MC). MATERIALS AND METHODS: We included 28 controls and 21 persons with MC. FLAIR, T2, and PD-weighted brain MRI scans were acquired at 1.5 Tesla, followed by semi-automated segmentation of the lateral and third ventricles, and local shape difference analysis based on growing and adaptive meshes. Ventricular meshes were used to highlight local areas with significant differences between controls and persons with MC, determined by permutation tests with a predefined threshold (P = 0.01). RESULTS: Compared with control subjects, relevant differences were found in the shape of the ventricular surface adjacent to the thalamus and corona radiata in persons with MC. Before correction for multiple comparisons, relevant differences were also found in the shape of the ventricular surface adjacent to the corpus callosum, hippocampus, and amydala. CONCLUSION: Our findings suggest the presence of localized structural brain differences in patients with subjective memory complaints in the thalamus and the corona radiata.
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Algoritmos , Encéfalo/patología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Trastornos de la Memoria/patología , Reconocimiento de Normas Patrones Automatizadas/métodos , Anciano , Atrofia/patología , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
This exploratory follow-up study investigated whether EEG parameters can predict future cognitive performance. Forty elderly subjects, ranging from cognitively unimpaired to those with Alzheimer disease underwent EEG registration at baseline and neuropsychological examination at both baseline and follow-up. We assessed relations between EEG measures and future cognitive performance (i.e., global cognition, memory, language, and executive functioning) controlling for age, follow-up time, and baseline cognitive performance. Regression models were constructed to predict performance on the Cambridge Cognitive Examination, a widely used tool within dementia screenings. Baseline EEG measures, i.e., increased theta activity (4-8 Hz) during eyes closed and less alpha reactivity (8-13 Hz) during eyes open and memory activation, indicated lower global cognitive, language (trend significant), and executive performance at follow-up. A regression model combining baseline cognitive and EEG measures provided the best prediction of future Cambridge Cognitive Examination performance (93%). EEG and cognitive measures alone predicted, respectively, 43% and 92% of variance. EEG and cognitive measures combined provided the best prediction of future cognitive performance. Although the "cognition only" model showed similar predictive power, the EEG provided significant additional value. The added value of EEG registration in the diagnostic work-up of dementia should be further assessed in larger samples.
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Envejecimiento/fisiología , Trastornos del Conocimiento/fisiopatología , Cognición/fisiología , Electroencefalografía/métodos , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Trastornos del Conocimiento/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Análisis de Regresión , Estudios RetrospectivosRESUMEN
Interleukin-1beta (IL-1beta) is present in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1Ra) moderates the induction of experimental autoimmune encephalomyelitis (EAE). Here, we show that families that are characterized by high IL-1beta over IL-1Ra production ratio are at 2.2-fold (95% CI, 1.0-4.8; p=0.05) increased risk to have a patient relative with relapse-onset MS than families with a low ratio. It is also related to the reduction of volumetric magnetization transfer ratio (MTR) histogram height, a measure of parenchymal integrity (p=0.04). Those families who combine a high IL-1beta over IL-1Ra ratio with a high tumor necrosis factor (TNF) over IL-10 production ratio have a 6.2-fold (95% CI, 1.8-21; p=0.002) increased risk. Innate production of IL-1beta and IL-1Ra is not related to the outcome of primary progressive MS. Taq1 polymorphism in the IL-1beta gene and the variable number of tandem repeats (VNTR) polymorphism of 86-base pairs within the IL-1Ra gene cannot explain these findings.
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Interleucina-1/genética , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Esclerosis Múltiple Recurrente-Remitente/genética , Sialoglicoproteínas/genética , Adulto , Anciano , Progresión de la Enfermedad , Exones , Femenino , Predisposición Genética a la Enfermedad , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Humanos , Proteína Antagonista del Receptor de Interleucina 1 , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/inmunología , Polimorfismo Genético , Factores de Riesgo , Secuencias Repetidas en TándemRESUMEN
We aimed to investigate volumetry of the medial temporal lobe in patients with subjective memory complaints without any cognitive impairment. This study included 20 patients with subjective memory complaints and normal cognitive function and 28 controls without memory complaints. Volumes of the hippocampus and parahippocampal gyrus (PHG) were measured using coronal T1-weighted MR images. Cognitive functions were assessed using the Cambridge Cognitive Examination. Depressive symptoms were assessed using the Geriatric Depression Scale. Differences between groups were analysed using t-tests. Patients with subjective memory complaints had a higher education and more depressive symptoms than controls ( p < 0.01). Moreover, they had smaller left hippocampal volumes than controls ( p < 0.01). There were no differences between groups in the volume of the right hippocampus or PHG. There was a moderate association between the volume of left hippocampus and left PHG and memory-score (r = 0.32, p = 0.03; r = 0.34, p = 0.02). We concluded that memory complaints in patients without any cognitive impairment were associated with smaller left hippocampal volumes and more depressive symptoms. These preliminary results suggest that memory complaints may reflect minimal brain deficits associated with impending dementia, depression or a combination of both disorders.
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Cognición/fisiología , Hipocampo/patología , Trastornos de la Memoria/patología , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Depresión/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Pruebas Neuropsicológicas , Giro Parahipocampal/patología , Análisis de Regresión , Lóbulo Temporal/patología , Lóbulo Temporal/fisiopatologíaRESUMEN
Among the 12 systemic lupus erythematosus (SLE)-related central nervous system (CNS) syndromes defined by the American College of Rheumatology (ACR), demyelinating syndrome and myelopathy are two of the less prevalent and more poorly understood ones. One important issue concerning demyelinating disease in SLE is that it can be easily misdiagnosed with other central nervous system demyelinating disorders such as multiple sclerosis (MS). A clinically isolated neurological syndrome can be the presenting feature before other concomitant symptoms of SLE appear or definite MS is diagnosed. Although challenging, some diagnostic tests used in clinical practice and research may help to differentiate between these entities. These tests have improved the understanding of the pathogenesis in these diseases, but some points, such as the role of antiphospholipid antibodies in SLE-associated transverse myelitis, remain unclear and are a matter of ongoing debate. This review discusses clinical, pathophysiological, radiological and therapeutic concepts of demyelinating disease of the CNS in SLE, focussing on its differentiation from MS and its relation with other CNS demyelinating processes, such as transverse myelitis, optic neuritis and neuromyelitis optica.
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Enfermedades Autoinmunes Desmielinizantes SNC/etiología , Lupus Eritematoso Sistémico/complicaciones , Esclerosis Múltiple/complicaciones , Anticuerpos Antifosfolípidos/sangre , Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico , Enfermedades Autoinmunes Desmielinizantes SNC/terapia , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/terapia , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/terapiaRESUMEN
OBJECTIVE: To describe clinical phenotypes in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Data were prospectively collected in the Leiden NPSLE referral clinic, where patients suspected of having NPSLE are assessed in a standardized multidisciplinary manner. In consensus meetings, all medical specialists agreed on therapeutic strategy based on the suspected pathogenetic mechanism of NPSLE in the individual patient. An algorithm illustrates the process of decision-making during the consensus meeting. Clinical phenotypes are described, classified by pathogenetic mechanism. RESULTS: One hundred consecutive patients were evaluated, of whom 71 had SLE (29 patients did not fulfill ≥ 4 American College of Rheumatology criteria) and 46 had NPSLE. Primary NPSLE was diagnosed in 38 patients (53%) and could be differentiated in 21 patients (55%) with inflammatory NPSLE who were advised on immunosuppressive therapy, 12 patients (32%) with ischemic NPSLE who were advised on anticoagulant therapy, and 5 patients (13%) with undefined NPSLE who were advised symptomatic treatment only. Cognitive dysfunction and higher level of disease activity were associated with inflammatory NPSLE. Although presence of immunoglobulin G anticardiolipin antibodies and abnormalities on magnetic resonance imaging (MRI) were associated with ischemic NPSLE, abnormalities on MRI lacked specificity to distinguish phenotypes. A history of renal disease and use of corticosteroids were associated with secondary NPSLE. CONCLUSION: We describe multidisciplinary consensus as a standard for diagnosing and defining phenotypes in NPSLE. These phenotypes show specific characteristics, which can be used to support diagnosis and guide therapeutic decisions. Clinical phenotyping and selection of patients becomes increasingly important when advances in experimental science lead to new targets for therapy in NPSLE.
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Algoritmos , Anticoagulantes/uso terapéutico , Inmunosupresores/uso terapéutico , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/tratamiento farmacológico , Fenotipo , Adulto , Anticuerpos Antiidiotipos/sangre , Anticuerpos Antiidiotipos/inmunología , Cardiolipinas/inmunología , Trastornos del Conocimiento/epidemiología , Femenino , Humanos , Inmunoglobulina G/sangre , Incidencia , Vasculitis por Lupus del Sistema Nervioso Central/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Países Bajos , Estudios ProspectivosRESUMEN
Research into the pathologic mechanisms of neurodegenerative diseases has revealed that CREB binding protein (CBP) plays an important role in cognitive dysfunction. Loss of one copy of this gene leads to a syndrome with severe cognitive dysfunction. We investigated the association between four common variants in the CBP gene and cognitive function in 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Baseline associations between genetic variation and cognitive function were assessed with linear regression. Longitudinal associations were assessed with linear mixed models. All analyses were adjusted for sex, age, education, country, version of test, and pravastatin use. The intron 4CT and intron 3AC polymorphisms in the CBP gene were associated with better cognitive performance at baseline and during follow-up. Furthermore, the haplotype with the variant alleles of these two polymorphisms also showed a protective effect on cognitive function in all cognitive domains (all p<0.03). Genetic variation in the CBP gene is associated with better cognitive performance in an elderly population. Future research is necessary to investigate the effect of these polymorphisms on the expression of CBP levels and how these polymorphisms affect the gene expression mediated by CBP.
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Proteína de Unión a CREB/genética , Cognición/fisiología , Epigenómica , Polimorfismo de Nucleótido Simple/genética , Enfermedades Vasculares/fisiopatología , Anciano , Anciano de 80 o más Años , Cognición/efectos de los fármacos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Modelos Lineales , Estudios Longitudinales , Masculino , Pruebas Neuropsicológicas , Pravastatina/uso terapéutico , Enfermedades Vasculares/tratamiento farmacológicoRESUMEN
Many efforts have been directed at negating the influence of electromyographic (EMG) activity on the EEG, especially in elderly demented patients. We wondered whether these "artifacts" might reflect cognitive and behavioural aspects of dementia. In this pilot study, 11 patients with probable Alzheimer's disease (AD), 13 with amnestic mild cognitive impairment (MCI) and 13 controls underwent EEG registration. As EMG measures, we used frontal and temporal 50-70 Hz activity. We found that the EEGs of AD patients displayed more theta activity, less alpha reactivity, and more frontal EMG than controls. Interestingly, increased EMG activity indicated more cognitive impairment and more depressive complaints. EEG variables on the whole distinguished better between groups than EMG variables, but an EMG variable was best for the distinction between MCI and controls. Our results suggest that EMG activity in the EEG could be more than noise; it differs systematically between groups and may reflect different cerebral functions than the EEG.
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OBJECTIVE: To investigate the relationship between fasting glucose levels, insulin resistance, and cognitive impairment in old age. Diabetes is associated with cognitive impairment in older people. However, the link between elevated fasting glucose levels and insulin resistance in nondiabetic individuals, and the risk of cognitive impairment is unclear. RESEARCH DESIGN AND METHODS: We analyzed data from, in total, 8,447 participants in two independent prospective studies: the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5,019 participants, aged 69-84 years, and the Rotterdam Study, 3,428 participants, aged 61-97 years. Fasting glucose levels were assessed at baseline in both studies; fasting insulin levels were assessed in the Rotterdam Study only. Cognitive function was assessed in both studies at baseline and during follow-up. RESULTS: Subjects with diabetes had impaired cognitive function at baseline. In contrast, in people without a history of diabetes, there was no clear association between baseline fasting glucose levels and executive function and memory, nor was there a consistent relationship between elevated baseline fasting glucose levels and the rate of cognitive decline in either cohort. Insulin resistance (homeostasis model assessment index) was also unrelated to cognitive function and decline. CONCLUSIONS: Elevated fasting glucose levels and insulin resistance are not associated with worse cognitive function in older people without a history of diabetes. These data suggest either that there is a threshold for effects of dysglycemia on cognitive function or that factors other than hyperglycemia contribute to cognitive impairment in individuals with frank diabetes.
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Cognición/fisiología , Diabetes Mellitus/fisiopatología , Hiperglucemia/fisiopatología , Resistencia a la Insulina , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Ayuno , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de RiesgoRESUMEN
Observational studies have given conflicting results about the effect of statins in preventing dementia and cognitive decline. Moreover, observational studies are subject to prescription bias, making it hard to draw definite conclusions from them. Randomized controlled trials are therefore the preferred study design to investigate the association between statins and cognition. Here we present detailed cognitive outcomes from the randomized placebo-controlled PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cognitive function was assessed repeatedly in all 5,804 PROSPER participants at six different time points during the study using four neuropsychological performance tests. After a mean follow-up period of 42 months, no difference in cognitive decline at any of the cognitive domains was found in subjects treated with pravastatin compared to placebo (all p > 0.05). Pravastatin treatment in old age did not affect cognitive decline during a 3 year follow-up period. Employing statin therapy in the elderly in an attempt to prevent cognitive decline therefore seems to be futile.
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Envejecimiento/efectos de los fármacos , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/prevención & control , Cognición/efectos de los fármacos , Nootrópicos/uso terapéutico , Pravastatina/uso terapéutico , Anciano , Anticolesterolemiantes/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pruebas Neuropsicológicas , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
In this work, we aimed at correlating focal atrophy in periventricular structures with cognitive function, in the spectrum from healthy subjects to severe Alzheimer disease: 28 subjects with normal cognition and 84 patients presenting various degrees of cognitive impairment were included in the study. The cognitive level of each subject was assessed with the Mini-Mental State Examination (MMSE). Atrophy in periventricular structures was inferred by modeling and analyzing local shape variations of brain ventricles: for a given subject, we distinguished between the severity of atrophy, estimated as local enlargement (in mm) of the ventricular surface relative to an average normal subject, and the extent of atrophy, defined as the percentage of the ventricular surface (global or per anatomical region) significantly different from an average control. Linear regression across subjects was performed to evaluate the correlation between atrophy and MMSE score. The severity of atrophy showed good correlation with MMSE score in the left thalamus, the left temporal horn, the left corona radiata, and the right caudate nuclei. The extent of atrophy showed no significant correlations. In conclusion, the MMSE scores correlate with localized depth of atrophy in well-defined periventricular structures.
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Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Ventrículos Cerebrales/anatomía & histología , Ventrículos Cerebrales/patología , Cognición/fisiología , Pruebas Neuropsicológicas , Anciano , Atrofia , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/psicología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Modelos Estadísticos , Valores de ReferenciaRESUMEN
OBJECTIVE: To investigate the independent associations between medial temporal lobe atrophy and white matter hyperintensities (WMH) and cognitive functions in the elderly. METHODS: Cognitive functions of 41 Alzheimer's disease patients, 20 patients with mild cognitive impairment and 28 elderly subjects without memory complaints were assessed using a neuropsychological test battery. Quantitative MRI measures of medial temporal lobe volume and WMH were obtained. Multiple regression analyses were performed to assess the independent contribution of MRI measures to impairment in several cognitive functions. RESULTS: Scores on the Wechsler Memory Scale and Trails B depended selectively on medial temporal lobe volume, whereas WMH selectively contributed to performance on Trails A. Medial temporal lobe volume and WMH both contributed to scores on the Cambridge Cognitive Examination and the Boston naming task. CONCLUSIONS: MRI measures suggestive of Alzheimer-type pathology and microvascular pathology independently contribute to cognitive decline at old age. Memory impairment as measured using the Wechsler Memory Scale and performance on Trails B primarily depended on medial temporal lobe atrophy. Psychomotor slowness, as measured using Trails A, mainly depended on WMH. These results suggest that vascular pathology and Alzheimer-type pathology each have specific cognitive correlates.
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Encéfalo/patología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/psicología , Imagen por Resonancia Magnética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Atrofia , Progresión de la Enfermedad , Femenino , Humanos , Lenguaje , Masculino , Memoria/fisiología , Pruebas Neuropsicológicas , Desempeño Psicomotor , Análisis de Regresión , Lóbulo Temporal/patologíaRESUMEN
PURPOSE: To prospectively compare indicators of structural brain damage and total cerebral blood flow in patients with late-onset dementia, subjects of the same age with optimal cognitive function, and young subjects. MATERIALS AND METHODS: The institutional ethics committee approved the studies, and all participants (or their guardians) gave informed consent. The test group included 17 patients older than 75 years (four men, 13 women; median age, 83 years) and with a diagnosis of dementia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The control group included 16 subjects (four men, 12 women; median age, 87 years) with optimal cognitive function, who were selected from among 599 elderly subjects enrolled in a population-based follow-up study, and 15 young healthy subjects (seven men, eight women; median age, 29 years). Measurements of intracranial and total brain volumes, structural brain damage, and cerebral blood flow were obtained with magnetic resonance imaging. Mean values were compared with the t test; medians, with the Mann-Whitney U test. RESULTS: Values for total brain volume were significantly smaller in elderly subjects (P < .001) but did not differ significantly between patients with dementia and subjects of the same age with optimal cognitive function (P = .69). Among the elderly, significantly higher scores for number and extent of white matter areas of signal hyperintensity (P = .028) and lower magnetization transfer ratios (P = .016) indicated greater structural brain damage in those with dementia. Cerebral blood flow was 246 mL/min lower (P < .001) in elderly subjects than in young subjects. In patients with dementia, cerebral blood flow was 108 mL/min lower than that in subjects of the same age with optimal cognitive function (551 vs 443 mL/min, P < .001). CONCLUSION: The combined observations of more structural brain damage and lower cerebral blood flow in demented elderly individuals than in subjects of the same age with optimal cognitive function support the hypothesis that vascular factors contribute to dementia in old age.
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Envejecimiento/fisiología , Circulación Cerebrovascular/fisiología , Demencia/patología , Imagen por Resonancia Magnética/métodos , Anciano , Anciano de 80 o más Años , Demencia/fisiopatología , Femenino , Humanos , Modelos Logísticos , Masculino , Estudios Prospectivos , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. METHODS: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. RESULTS: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. CONCLUSIONS: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline.
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Encéfalo/patología , Trastornos del Conocimiento/patología , Trastornos de la Memoria/patología , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Pronóstico , Estudios Prospectivos , Lóbulo Temporal/patologíaRESUMEN
The purpose of this study was to assess whether structural brain damage as detected by volumetric magnetization transfer imaging (MTI) is present in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and, if so, whether these abnormalities are global in character or restricted to the temporal lobe. Volumetric MTI analysis of the whole brain and temporal and frontal lobes was performed in 25 patients with probable AD, in 13 patients with MCI, and in 28 controls. Magnetization transfer ratio (MTR) histograms were produced, from which we derived measures for structural brain damage and atrophy. The peak heights of the MTR histograms of MCI and AD patients were lower than those of controls for the whole brain and temporal and frontal lobes, reflecting structural brain damage. AD patients had more atrophy than controls in all regions that were studied. MCI patients differed from controls for temporal lobe atrophy only. Volumetric MTI demonstrates structural changes that are related to cognitive decline in large parts of the brain of AD patients. Moreover, structural changes also were observed in MCI patients, indicating that widespread brain damage can be demonstrated before patients are clinically demented.