RESUMEN
BACKGROUND: White matter hyperintensities (WMHs) are related to cognitive dysfunction in the general population. The clinical relevance of WMHs in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) is, however, unclear. OBJECTIVE: This meta-analysis aimed to quantify the association of WMHs and specific cognitive domains in patients with MCI or AD. METHODS: PubMed (January 1990-January 2017) was searched for studies that used MRI to quantify WMHs, and measured cognitive functioning (≥1 predefined cognitive domain with ≥1 test) in a well-defined population of persons diagnosed with MCI or AD. Fischer's Z was used as the common metric for effect size. Modifying effects of demographics, MMSE, and WMH location were examined. RESULTS: Twelve cross-sectional studies on AD (total nâ=â1,370, median age 75 years) and 10 studies on MCI (9 cross-sectional, 1 longitudinal; total nâ=â2,286, median age 73 years) were included. The association between WMHs and overall cognition was significantly stronger for MCI (-0.25, -0.36 to -0.14) than for AD (-0.11, -0.14 to -0.08; QMâ=â10.7, pâ<â0.05). For both groups, largest effect sizes were found in attention and executive functions (-0.26, -0.36 to -0.15) and processing speed (-0.21, -0.35 to -0.12). No significant modifying effects of age and gender were found. CONCLUSION: WMHs have a medium-sized association with different cognitive functions in patients with MCI and a small, but statistically significant, association with cognition in AD. These result underscore the role of co-occurring vascular brain damage in MCI and AD.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/psicología , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/psicología , Sustancia Blanca/diagnóstico por imagen , Humanos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Evidence suggests that lacunar infarcts have different etiologies, possibly related to their anatomical location and vascular territory. We investigated the risk factor profiles of patients with new lacunar infarcts in the basal ganglia and deep white matter. METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a prospective cohort on brain changes on MRI in patients with symptomatic atherosclerotic disease, 679 patients (57 ± 9 years) had vascular screening and MRI at baseline and after a mean follow-up of 3.9 years. We investigated the association between vascular risk factors at baseline and appearance of new lacunar infarcts in the basal ganglia and deep white matter at follow-up. RESULTS: New lacunar infarcts appeared in 44 patients in the basal ganglia and in 37 patients in the deep white matter. In multivariable analysis, older age, history of cerebrovascular disease, and baseline white matter hyperintensity (WMH) volume were associated with increased risk of new lacunar infarcts in both locations. Hyperhomocysteinemia was associated with increased risk of lacunar infarcts in the basal ganglia (relative risk [RR] 2.0; 95% CI 1.0-4.2), whereas carotid stenosis >70% (RR 2.5; 95% CI 1.2-5.0), smoking (per 10 pack-year: RR 1.1; 95% CI 1.0-1.3), hypertension (RR 3.4; 95% CI 1.2-9.7), and progression of WMH volume (RR 2.4; 95% CI 1.1-5.2) were associated with increased risk of lacunar infarcts in the deep white matter. CONCLUSIONS: The different risk factor profiles for new lacunar infarcts in basal ganglia and deep white matter indicate different etiologies. The independent association between progression of WMH and new deep white matter lacunar infarcts suggest a common etiology for these radiological abnormalities.
Asunto(s)
Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/etiología , Ganglios Basales/diagnóstico por imagen , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/etiología , Imagen por Resonancia Magnética , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/etiología , Sustancia Blanca/diagnóstico por imagen , Factores de Edad , Anciano , Estenosis Carotídea/complicaciones , Distribución de Chi-Cuadrado , Femenino , Humanos , Hiperhomocisteinemia/complicaciones , Hipertensión/complicaciones , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Fumar/efectos adversosRESUMEN
BACKGROUND AND PURPOSE: Small cerebellar infarct cavities have been recently found on magnetic resonance imaging (MRI) to preferentially involve the cerebellar cortex, but epidemiological studies are lacking. We aimed to determine the prevalence and risk factor profiles of cerebellar cortical infarct cavities (≤1.5 cm) as well as their association with MRI markers of cerebrovascular disease and functioning. METHODS: We analyzed the 1.5 Tesla MRI of 636 patients (mean age, 62±9 years; 81% men) from the Second Manifestations of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study. Logistic regression analyses were performed to estimate the associations of age, sex, vascular risk factors, MRI markers of cerebrovascular disease, and functioning with cerebellar cortical cavities, adjusted for age and sex. RESULTS: Cerebellar cortical infarct cavities occurred on MRI in 10% of patients and were significantly associated with age, intima-media thickness (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.7), high levels of homocysteinemia (OR, 1.8; 95% CI, 1.0-3.3), cortical infarcts (OR, 2.9; 95% CI, 1.6-5.4), gray matter lacunes of presumed vascular origin (OR, 3.0; 95% CI, 1.6-5.8), brain stem infarcts (OR, 5.1; 95% CI, 1.9-13.6), and decreased brain parenchymal fraction (OR, 0.84; 95% CI, 0.74-0.94), but not with white matter hyperintensities (OR, 1.2; 95% CI, 0.8-1.8) or white matter lacunes of presumed vascular origin (OR, 1.1; 95% CI, 0.5-2.5). They were also associated with worse physical functioning (OR, 0.96; 95% CI, 0.94 to -0.99) [corrected] but not with mental functioning. CONCLUSIONS: Cerebellar cortical infarct cavities are far more common than previously assumed based on symptomatic case series and are associated with markers of atherothromboembolic cerebrovascular disease.
Asunto(s)
Infarto Encefálico/diagnóstico , Infarto Encefálico/metabolismo , Corteza Cerebelosa/metabolismo , Corteza Cerebelosa/patología , Imagen por Resonancia Magnética , Adulto , Anciano , Anciano de 80 o más Años , Trastornos Cerebrovasculares , Estudios de Cohortes , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: Previous studies on cerebellar infarcts have been largely restricted to acute infarcts in patients with clinical symptoms, and cerebellar infarcts have been evaluated with the almost exclusive use of transversal MR images. We aimed to document the occurrence and 3D-imaging patterns of cerebellar infarcts presenting as an incidental finding on MRI. METHODS: We analysed the 1.5 Tesla MRI, including 3D T1-weighted datasets, of 636 patients (mean age 62 ± 9 years, 81% male) from the SMART-Medea study. Cerebellar infarct analyses included an assessment of size, cavitation and gliosis, of grey and white matter involvement, and of infarct topography. RESULTS: One or more cerebellar infarcts (mean 1.97; range 1-11) were detected in 70 out of 636 patients (11%), with a total amount of 138 infarcts identified, 135 of which showed evidence of cavitation. The average mean axial diameter was 7 mm (range 2-54 mm), and 131 infarcts (95%) were smaller than 20 mm. Hundred-thirty-four infarcts (97%) involved the cortex, of which 12 in combination with subcortical white matter. No infarcts were restricted to subcortical branches of white matter. Small cortical infarcts involved the apex of a deep (pattern 1) or shallow fissure (pattern 2), or occurred alongside one (pattern 3) or opposite sides (pattern 4) of a fissure. Most (87%) cerebellar infarcts were situated in the posterior lobe. CONCLUSIONS: Small cerebellar infarcts proved to be much more common than larger infarcts, and preferentially involved the cortex. Small cortical infarcts predominantly involved the posterior lobes, showed sparing of subcortical white matter and occurred in characteristic topographic patterns.
Asunto(s)
Corteza Cerebelosa/patología , Infarto Cerebral/patología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: We aimed to quantify the effects of white matter hyperintensities (WMHs) on specific cognitive functions with particular attention to WMH progression and localization. METHODS: PubMed (January 1990-July 2013) and bibliographies from included articles were used. Studies that were included (1) used MRI; (2) had a population-based or case-control design with a healthy control group that could be used for analysis; (3) matched/adjusted for age, sex, and education; and (4) addressed ≥1 predefined cognitive domains with ≥1 validated neuropsychological tests. Data were independently extracted by 2 investigators. Pearson r was extracted/calculated and used as the common metric for the effect size across studies. RESULTS: Twenty-three cross-sectional and 14 longitudinal studies were included with a total of 8,685 and 7,731 participants. Presence of WMHs was significantly associated with concurrent cognitive deficits in all examined domains: general intelligence (Fisher z -0.10, 95% confidence interval [CI] -0.19 to -0.04), memory (-0.08, -0.13 to -0.06), processing speed (-0.11, -0.17 to -0.07), attention and executive functions (-0.11, -0.16 to -0.07), and perception/construction (-0.15, -0.21 to -0.07). Similar effect sizes were observed for cognitive decline over time. WMH progression was associated with greater cognitive decline, particularly for general intelligence (Fisher z -0.31, 95% CI -0.5 to -0.02) and attention and executive functions (-0.32, -0.34 to -0.28). CONCLUSIONS: The small but robust and consistent effects of WMHs on all cognitive domains suggest a more global effect on cognition than previously thought. Progression of WMHs was associated with even worse cognitive functioning, most pronounced in attention and executive functioning.
Asunto(s)
Trastornos del Conocimiento , Progresión de la Enfermedad , Leucoencefalopatías , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Humanos , Leucoencefalopatías/complicaciones , Leucoencefalopatías/patología , Leucoencefalopatías/fisiopatologíaRESUMEN
OBJECTIVES: Assuming the involvement of homocysteine in a generalized small-vessel disease, we investigated the association of homocysteine levels with progression of white matter lesions, lacunar infarcts, and kidney disease. METHODS: Within the SMART-MR (Second Manifestations of ARTerial disease-Magnetic Resonance) Study, a prospective cohort study on brain aging in patients with symptomatic atherosclerotic disease, 663 patients (aged 57 ± 9 years) had vascular screening and 1.5-tesla MRI at baseline and after a mean follow-up of 3.9 years. Multiple regression analysis was used to estimate the longitudinal association between total homocysteine level, defined as a continuous variable and as hyperhomocysteinemia (the highest quintile of homocysteine), and progression of white matter lesion volume, lacunar infarcts, and estimated glomerular filtration rate. RESULTS: After adjusting for age, sex, follow-up time, and vascular risk factors, hyperhomocysteinemia was significantly associated with increased risk of white matter lesion progression (odds ratio 2.4, 95% confidence interval [CI] 1.5-4.1) and lower estimated glomerular filtration rate at follow-up (B = -3.4 mL/min, 95% CI -5.9 to -0.9) and borderline significantly associated with new lacunar infarcts (odds ratio 1.8, 95% CI 0.9-3.4). CONCLUSIONS: Our findings implicate a role for homocysteine in the development of a generalized small-vessel disease in which both brain and kidney are affected.
Asunto(s)
Encéfalo/patología , Trastornos Cerebrovasculares/sangre , Homocisteína/sangre , Hiperhomocisteinemia/patología , Enfermedades Renales/sangre , Fibras Nerviosas Mielínicas/patología , Factores de Edad , Anciano , Atrofia/sangre , Atrofia/complicaciones , Atrofia/patología , Trastornos Cerebrovasculares/complicaciones , Trastornos Cerebrovasculares/patología , Progresión de la Enfermedad , Femenino , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/complicaciones , Enfermedades Renales/complicaciones , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Factores SexualesRESUMEN
BACKGROUND: Homocysteine may be a modifiable risk factor for cognitive decline and brain atrophy, particularly in older persons. We examined whether homocysteine increased the risk for cognitive decline and brain atrophy, and evaluated the modifying effect of age. METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study-a prospective cohort study among patients with atherosclerotic disease-longitudinal analyses were performed in 663 patients (mean age: 57 ± 9 years; follow-up: 3.9 ± 0.4 years). At baseline and follow-up, brain segmentation on magnetic resonance imaging was used to quantify relative (%) cortical, ventricular, and global brain volumes, and z-scores of memory and executive functioning were calculated. Linear regression analysis was used to estimate associations of homocysteine (per standard deviation increase) and hyperhomocysteinemia (HHCY) with brain volumes, memory, and executive functioning at follow-up, adjusted for baseline brain volume, memory, and executive functioning, respectively, and age, sex, and vascular risk factors. Furthermore, interaction terms between homocysteine and age (continuous) were added. RESULTS: Significant interactions were observed between total plasma homocysteine (tHcy) and age with cortical, ventricular, and global brain volume (for all three measures: P < .05), and between HHCY and age with executive functioning (P = .04), and results were stratified by age. In patients aged ≥65 years, increasing tHcy level and HHCY were significantly associated with progression of ventricular enlargement (B = 0.07%, 95% confidence interval [CI]: 0.01% to 0.13% and B = 0.16%, 95% CI: 0.01% to 0.31%, respectively) and with a decline in executive function (B = -0.29, 95% CI: -0.54 to -0.04 and B = -0.84, 95% CI: -1.37 to -0.32, respectively). CONCLUSION: Elevated tHcy was related to progression of ventricular enlargement and increased the risk for a decline in executive functioning in older persons.
Asunto(s)
Ventrículos Cerebrales/metabolismo , Ventrículos Cerebrales/patología , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/patología , Homocisteína/sangre , Imagen por Resonancia Magnética , Anciano , Envejecimiento/patología , Aterosclerosis/epidemiología , Aterosclerosis/metabolismo , Aterosclerosis/patología , Atrofia/epidemiología , Atrofia/metabolismo , Atrofia/patología , Biomarcadores/sangre , Infarto Cerebral/epidemiología , Infarto Cerebral/metabolismo , Infarto Cerebral/patología , Trastornos del Conocimiento/epidemiología , Progresión de la Enfermedad , Función Ejecutiva , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND AND PURPOSE: Cerebral small vessel disease may be related to vascular and nonvascular pathology. We assessed whether lacunar infarcts and white matter lesions on MRI increased the risk of vascular and nonvascular death and future vascular events in patients with atherosclerotic disease. METHODS: Brain MRI was performed in 1309 patients with atherosclerotic disease from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study. Infarcts were scored visually and volumetric assessment of white matter lesion was performed. Patients were followed for a median of 4.5 years (range, 0.2 to 7.1 years) for death, ischemic stroke, and ischemic cardiac complications. RESULTS: Cox regression models showed that presence of lacunar infarcts (n=229) increased the risk of vascular (hazard ratio, 2.6; 95% CI, 1.4 to 4.9) and nonvascular death (hazard ratio, 2.7; 95% CI, 1.3 to 5.3), adjusted for age, sex, vascular risk factors, nonlacunar infarcts, and white matter lesion. These risks were similar for patients with silent lacunar infarcts. White matter lesion volume (relative to total intracranial volume) increased the risk of vascular death (hazard ratio per milliliter increase, 1.03; 95% CI, 1.01 to 1.05) and white matter lesions in the upper quintile compared with lower quintiles increased risk of ischemic stroke (hazard ratio, 2.6; 95% CI, 1.3 to 4.9). CONCLUSIONS: Cerebral small vessel disease, with or without a history of cerebrovascular disease, is associated with increased risk of death and ischemic stroke in patients with atherosclerotic disease.
Asunto(s)
Aterosclerosis/diagnóstico , Isquemia Encefálica/diagnóstico , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico , Imagen por Resonancia Magnética , Accidente Cerebrovascular/diagnóstico , Anciano , Aterosclerosis/complicaciones , Aterosclerosis/mortalidad , Isquemia Encefálica/complicaciones , Isquemia Encefálica/mortalidad , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/mortalidad , Trastornos Cerebrovasculares/complicaciones , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/mortalidad , Estudios de Cohortes , Femenino , Humanos , Leucoencefalopatías/complicaciones , Leucoencefalopatías/diagnóstico , Leucoencefalopatías/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/mortalidad , Accidente Vascular Cerebral Lacunar/complicaciones , Accidente Vascular Cerebral Lacunar/diagnóstico , Accidente Vascular Cerebral Lacunar/mortalidadRESUMEN
OBJECTIVE: High homocysteine level is a risk factor for atherosclerosis and has been associated with lacunar infarcts (LIs), white matter lesions (WML) and cognitive dysfunction. It is unclear whether homocysteine is associated with cerebral small vessel disease (cSVD) on top of pre-existent atherosclerosis. We evaluated the association between homocysteine and cSVD in a large cohort of patients with symptomatic atherosclerotic disease. METHODS: Within the SMART-MR study, a prospective cohort study of patients with symptomatic atherosclerotic disease, we estimated cross-sectional associations of total plasma homocysteine (THCY) and hyperhomocysteinemia (HHCY) with WML volume and presence of LI, using automated brain segmentation in MRIs of 1232 patients and cognitive function in 763 patients. WML were expressed as a logarithmic transformed percentage of total brain volume. RESULTS: Linear regression analyses adjusted for age, sex, vascular risk factors and extent of atherosclerosis showed that THCY and HHCY were significantly associated with larger WML volumes (B=0.01%: 95% CI 0.002-0.02%, and B=0.21%: 95% CI 0.04-0.39%). Increasing THCY was significantly associated with an increased risk of LIs (OR 1.04, 95% CI 1.01-1.07, per 1 µmol). Moreover, HHCY was associated with worse cognitive function (B=-0.12: 95% CI -0.22 to -0.01). CONCLUSION: In patients with symptomatic atherosclerotic disease, higher homocysteine levels are associated with higher WML volume, presence of LI and slightly worse cognitive function.
Asunto(s)
Aterosclerosis/sangre , Homocisteína/sangre , Imagen por Resonancia Magnética/métodos , Anciano , Encéfalo/patología , Trastornos del Conocimiento/sangre , Estudios de Cohortes , Estudios Transversales , Femenino , Homocisteína/metabolismo , Humanos , Hiperhomocisteinemia/sangre , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Factores de RiesgoRESUMEN
MRI equipment with a magnet having a field strength of 7 Tesla (7-T) has been in use for several years at the University Medical Centre, Utrecht, the Netherlands. 7-Tesla MR imaging provides new opportunities for imaging the brain and its vasculature. The enhanced resolution and the possibilities for angiography of the smallest cerebral vessels without using contrast media are particularly of interest for patients with cerebral small-vessel disease. Microthrombi may be visualised in the perforating cerebral arteries in patients with a lacunar infarct. This technique could have a considerable impact on the classification of several types of lacunar infarcts and could lead to better customised therapies.
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Infarto Encefálico/diagnóstico , Arterias Cerebrales/patología , Imagen por Resonancia Magnética/métodos , Infarto Encefálico/patología , Circulación Cerebrovascular , Humanos , Procesamiento de Imagen Asistido por Computador , Angiografía por Resonancia Magnética/métodos , Índice de Severidad de la EnfermedadRESUMEN
Cerebral amyloid angiopathy (CAA) is a common but often asymptomatic disease, characterized by deposition of amyloid in cerebral blood vessels. We describe the successful treatment of CAA encephalopathy with dexamethasone in a patient with CAA-related inflammation causing subacute progressive encephalopathy and seizures, which is an increasingly recognized subtype of CAA. The two pathological subtypes of CAA-related inflammation are described and a review of the literature is performed concerning immunosuppressive treatment of CAA-related inflammation with special attention to its pathological subtypes. Immunosuppressive therapy appears to be an appropriate treatment for CAA encephalopathy.
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Angiopatía Amiloide Cerebral/complicaciones , Angiopatía Amiloide Cerebral/tratamiento farmacológico , Esteroides/uso terapéutico , Anciano , Angiopatía Amiloide Cerebral/patología , Humanos , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
Vascular risk factors, such as type 2 diabetes mellitus, hypertension, dyslipidemia and obesity, have been associated with an increased risk of cognitive dysfunction, particularly in the elderly. The aim of this systematic review was to compare these risk factors with regard to the nature and magnitude of the associated cognitive decrements. Cross-sectional and longitudinal studies that assessed cognitive functioning in non-demented persons in relation to diabetes/impaired glucose metabolism (k = 36), hypertension (k = 24), dyslipidemia (k = 7) and obesity (k = 6) and that adjusted or matched for age, gender and education were included. When possible, effect sizes (Cohen's d) were computed per cognitive domain. Diabetes and hypertension were clearly associated with cognitive decrements; the results for obesity and dyslipidemia were less consistent. Effect sizes were moderate (median approximately -0.3) for all risk factors. Decline was found in all cognitive domains, although the effects on cognitive speed, mental flexibility and memory were most consistent. Methodological aspects of included studies and implications of these findings are discussed.
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Trastornos del Conocimiento/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Dislipidemias/fisiopatología , Hipertensión/fisiopatología , Obesidad/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Dislipidemias/complicaciones , Dislipidemias/metabolismo , Femenino , Glucosa/metabolismo , Humanos , Hipertensión/complicaciones , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/metabolismo , Adulto JovenRESUMEN
Vascular risk factors, such as type 2 diabetes, hypertension, obesity and dyslipidaemia often co-occur. Each of these factors has been associated with an increased risk of dementia, but it is uncertain which factor imposes the greatest risk. Moreover, the effect of age at time of exposure may differ across factors. This paper systematically reviews the evidence for the association of each of these risk factors with dementia. Longitudinal population-based studies that assessed the incidence of dementia in relation to diabetes (n=14), hypertension (n=13), dyslipidaemia (n=8) or obesity (n=9) were included. All four risk factors were indeed associated with an increased risk of dementia, but the results of studies on diabetes and obesity were most consistent. The magnitude of the effects was comparable across the risk factors, with odds ratios for 'any dementia' around 1.5. For hypertension, obesity and dyslipidaemia age appeared to modulate the association: the risk of dementia was generally largest in studies that measured the risk factor in midlife (compared to late life) and had a long follow-up time. At midlife, the population attributable risk of dementia was highest for hypertension, up to 30% of cases of late life dementia. Later in life diabetes appears to convey the highest risk of dementia. This review shows that vascular risk factors should be regarded as a major target for preventive measures, but that timing of such measures appears to be critical.