RESUMEN

INTRODUCTION: Co-occurrence of cerebrovascular disease and depression led to the "vascular depression hypothesis". White matter hyperintensities (WMHs) have been associated with depressive symptoms in population-based studies. We studied the association between small vessel disease and depressive symptoms in a memory clinic population. METHODS: We included >2000 patients with subjective cognitive decline (SCD), mild cognitive impairment, and Alzheimer's disease (AD). Magnetic resonance imaging was rated for WMHs, lacunes, and microbleeds. Depressive symptoms were assessed using the Geriatric Depression Scale. We performed logistic regression analysis. RESULTS: Depressive symptoms were present in AD: 17%; mild cognitive impairment: 25%; and SCD: 23%. SCD patients with WMHs showed higher propensity of depressive symptoms than AD patients with WMHs. AD patients with microbleeds were more likely to have depressive symptoms compared with AD patients without microbleeds (odds ratio = 1.70; 95% confidence interval: 1.08-2.68). DISCUSSION: Microbleeds are associated with depressive symptoms in AD, supporting a potential role of cerebral amyloid angiopathy in the occurrence of depressive symptoms in AD.

RESUMEN

We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2-8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini-Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language. Thickness (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal, cingulate, and occipital cortices. We used linear mixed models to estimate effects of cortical thickness on cognitive performance (dependent variables). There were no associations between cortical thickness and baseline cognition, but a faster subsequent rate of memory loss was associated with thinner cortex of the frontal [ß (SE) = 0.20 (0.07)], temporal [ß (SE) = 0.18 (0.07)], and occipital [ß (SE) = 0.22 (0.09)] cortices (all p < 0.05FDR). These findings illustrate that early cortical changes, particularly in the temporal cortex, herald incipient cognitive decline related to neurodegenerative diseases, most prominently Alzheimer's disease.

Asunto(s)

Enfermedad de Alzheimer/etiología , Corteza Cerebral/patología , Disfunción Cognitiva/patología , Disfunción Cognitiva/psicología , Memoria , Anciano , Corteza Cerebral/diagnóstico por imagen , Cognición , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/diagnóstico , Estudios de Cohortes , Femenino , Humanos , Lenguaje , Imagen por Resonancia Magnética , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad

RESUMEN

Gray matter networks are disrupted in Alzheimer's disease and related to cognitive impairment. However, it is still unclear whether these disruptions are associated with cognitive decline over time. Here, we studied this question in a large sample of patients with mild cognitive impairment with extensive longitudinal neuropsychological assessments. Gray matter networks were extracted from baseline structural magnetic resonance imaging, and we tested associations of network measures and cognitive decline in Mini-Mental State Examination and 5 cognitive domains (i.e., memory, attention, executive function, visuospatial, and language). Disrupted network properties were cross-sectionally related to worse cognitive impairment. Longitudinally, lower small-world coefficient values were associated with a steeper decline in almost all domains. Lower betweenness centrality values correlated with a faster decline in Mini-Mental State Examination and memory, and at a regional level, these associations were specific for the precuneus, medial frontal, and temporal cortex. Furthermore, network measures showed additive value over established biomarkers in predicting cognitive decline. Our results suggest that gray matter network measures might have use in identifying patients who will show fast disease progression.

Asunto(s)

Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/patología , Sustancia Gris/patología , Sustancia Gris/fisiopatología , Anciano , Disfunción Cognitiva/psicología , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad

RESUMEN

[This corrects the article on p. 213 in vol. 9, PMID: 28713264.].

RESUMEN

Background: White matter changes (WMC) are a common finding among older adults and patients with Parkinson's disease (PD), and have been associated with, e.g., gait deficits and executive dysfunction. How the factors age and PD influence WMC-related deficits is, to our best knowledge, not investigated to date. We hypothesized that advanced age and presence of PD leads to WMC-related symptoms while practicing tasks with a low complexity level, and low age and absence of PD leads to WMC-related symptoms while practicing tasks with a high complexity level. Methods: Hundred and thirty-eight participants [65 young persons without PD (50-69 years, yPn), 22 young PD patients (50-69 years, yPD), 36 old persons without PD (70-89 years, oPn) and 15 old PD patients (70-89 years, oPD)] were included. Presence and severity of WMC were determined with the modified Fazekas score. Velocity of walking under single and dual tasking conditions and the Trail Making Test (TMT) were used as gait and executive function parameters. Correlations between presence and severity of WMC, and gait and executive function parameters were tested in yPn, yPD, oPn, and oPD using Spearman's rank correlation, and significance between groups was evaluated with Fisher's z-transformed correlation coefficient. Results: yPn and yPD, as well as oPn and oPD did not differ regarding demographic and clinical parameters. Severity of WMC was not significantly different between groups. yPn and yPD displayed significant correlations of WMC with executive function parameters at low levels of task complexity, oPn at intermediate, and oPD at high complexity levels. Conclusion: This study argues for a relevant association of age and PD-related brain pathology with WMC-related gait and executive function deficits.

RESUMEN

Aim: To assess the associations of age and diagnosis with visual ratings of medial temporal lobe atrophy (MTA), parietal atrophy (PA), global cortical atrophy (GCA), and white matter hyperintensities (WMH) and to investigate their clinical value in a large memory clinic cohort. Methods: We included 2,934 patients (age 67 ± 9 years; 1,391 [47%] female; MMSE 24 ± 5) from the Amsterdam Dementia Cohort (1,347 dementia due to Alzheimer's disease [AD]; 681 mild cognitive impairment [MCI]; 906 controls with subjective cognitive decline). We analyzed the effect of age, APOE e4 and diagnosis on visual ratings using linear regression analyses. Subsequently, we compared diagnostic and predictive value in three age-groups (<65 years, 65-75 years, and >75 years). Results: Linear regression analyses showed main effects of age and diagnosis and an interaction age*diagnosis for MTA, PA, and GCA. For MTA the interaction effect indicated steeper age effects in MCI and AD than in controls. PA and GCA increased with age in MCI and controls, while AD patients have a high score, regardless of age. For WMH we found a main effect of age, but not of diagnosis. For MTA, GCA and PA, diagnostic value was best in patients <65 years (optimal cut-off: ≥1). PA and GCA only discriminated in patients <65 years and MTA in patients <75 years. WMH did not discriminate at all. Taking into account APOE did not affect the identified optimal cut-offs. When we used these scales to predict progression in MCI using Cox proportional hazard models, only MTA (cut-off ≥2) had any predictive value, restricted to patients >75 years. Conclusion: Visual ratings of atrophy and WMH were differently affected by age and diagnosis, requiring an age-specific approach in clinical practice. Their diagnostic value seems strongest in younger patients.

RESUMEN

OBJECTIVE: To determine whether lower cerebral blood flow (CBF) is associated with faster cognitive decline in patients with Alzheimer's disease (AD). METHODS: We included 88 patients with dementia due to AD from the Amsterdam Dementia Cohort. Mean follow-up was 2 ± 1 years. Linear mixed models were used to determine associations of lower whole brain and regional pseudo-continuous arterial spin labelling measured CBF with rate of cognitive decline as measured with repeated mini-mental state examination (MMSE). Model 1 was adjusted for age, sex, and education. Model 2 was additionally adjusted for normalized gray matter volume, medial temporal lobe atrophy, white matter hyperintensities, microbleeds, and lacunes. Analyses were repeated after partial volume correction (PVC) of CBF. Statistical significance was set at p ≤ 0.05. RESULTS: Patients were 65 ± 7 years old, 44 (50 %) were women, and mean baseline MMSE was 22 ± 4. Annual decline (ß[SE]) on the MMSE was estimated at -2.11 (0.25) points per year. Lower whole brain (ß[SE]-0.50[0.25]; p ≤ 0.05) and parietal (ß[SE]-0.59[0.25]; p < 0.05) CBF were associated with faster cognitive decline. PVC cortical CBF was not associated with cognitive decline. CONCLUSIONS: Lower CBF, in particular in the posterior brain regions, may have value as a prognostic marker for rate of cognitive decline in AD. KEY POINTS: • In AD, lower CBF is associated with more rapid cognitive decline. • Decreasing CBF does not reach a plateau early in AD. • PcASL-CFB has additive value to conventional structural MRI measures in AD.

Asunto(s)

Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular , Anciano , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Atrofia/patología , Encéfalo/patología , Progresión de la Enfermedad , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Modelos Lineales , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Marcadores de Spin , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/patología , Factores de Tiempo

RESUMEN

INTRODUCTION: We examined the association between decreased cerebral blood flow (CBF) and cognitive impairment in Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive decline (SCD). METHODS: We included 161 AD, 95 MCI, and 143 SCD patients from the Amsterdam Dementia Cohort. We used 3-T pseudo-continuous arterial spin labeling to estimate whole-brain and regional partial volume-corrected CBF. Neuropsychological tests covered global cognition and five cognitive domains. Associations were investigated using linear regression analyses. RESULTS: In the whole sample, reduced overall and regional CBF was associated with impairment in all cognitive domains. We found significant interactions between diagnosis and CBF for language and between diagnosis and parietal CBF for global cognition and executive functioning. Stratification showed that decreased CBF was associated with worse performance in AD patients but not in MCI or SCD. DISCUSSION: Our results suggest that CBF may have potential as a functional marker of disease severity.

Asunto(s)

Enfermedad de Alzheimer/fisiopatología , Encéfalo/patología , Circulación Cerebrovascular/fisiología , Trastornos del Conocimiento/patología , Cognición/fisiología , Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Países Bajos , Pruebas Neuropsicológicas/estadística & datos numéricos , Marcadores de Spin

RESUMEN

Purpose To investigate whether multivariate pattern recognition analysis of arterial spin labeling (ASL) perfusion maps can be used for classification and single-subject prediction of patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) and subjects with subjective cognitive decline (SCD) after using the W score method to remove confounding effects of sex and age. Materials and Methods Pseudocontinuous 3.0-T ASL images were acquired in 100 patients with probable AD; 60 patients with MCI, of whom 12 remained stable, 12 were converted to a diagnosis of AD, and 36 had no follow-up; 100 subjects with SCD; and 26 healthy control subjects. The AD, MCI, and SCD groups were divided into a sex- and age-matched training set (n = 130) and an independent prediction set (n = 130). Standardized perfusion scores adjusted for age and sex (W scores) were computed per voxel for each participant. Training of a support vector machine classifier was performed with diagnostic status and perfusion maps. Discrimination maps were extracted and used for single-subject classification in the prediction set. Prediction performance was assessed with receiver operating characteristic (ROC) analysis to generate an area under the ROC curve (AUC) and sensitivity and specificity distribution. Results Single-subject diagnosis in the prediction set by using the discrimination maps yielded excellent performance for AD versus SCD (AUC, 0.96; P < .01), good performance for AD versus MCI (AUC, 0.89; P < .01), and poor performance for MCI versus SCD (AUC, 0.63; P = .06). Application of the AD versus SCD discrimination map for prediction of MCI subgroups resulted in good performance for patients with MCI diagnosis converted to AD versus subjects with SCD (AUC, 0.84; P < .01) and fair performance for patients with MCI diagnosis converted to AD versus those with stable MCI (AUC, 0.71; P > .05). Conclusion With automated methods, age- and sex-adjusted ASL perfusion maps can be used to classify and predict diagnosis of AD, conversion of MCI to AD, stable MCI, and SCD with good to excellent accuracy and AUC values. © RSNA, 2016.

Asunto(s)

Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/diagnóstico , Marcadores de Spin , Anciano , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Área Bajo la Curva , Disfunción Cognitiva/fisiopatología , Diagnóstico Precoz , Femenino , Humanos , Aprendizaje Automático , Angiografía por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Reconocimiento Visual de Modelos

RESUMEN

BACKGROUND AND PURPOSE: We aimed to identify prognostic and associated factors of incident cerebral microbleeds (CMBs) in intracerebral hemorrhage (ICH) survivors. METHODS: Observational prospective cohort of 168 ICH survivors who underwent 1.5T magnetic resonance imaging at ICH onset and during follow-up (median scan interval, 3.4; interquartile range, 1.4-4.7) years. We used logistic regression adjusted for age, sex, and scan interval. Analyses were stratified according to the index ICH location (58 lobar ICH, 103 nonlobar ICH, excluding patients with multiple or unclassifiable ICH). RESULTS: Eighty-nine (53%) patients had CMBs at ICH onset, and 80 (48%) exhibited incident CMBs during follow-up. Predictors of incident CMBs at ICH onset were ≥1 CMBs (adjusted odds ratio [aOR], 2.27; 95% confidence interval [CI], 1.18-4.35), old radiological macrohemorrhage (aOR, 6.78; 95% CI, 2.76-16.68), and CMBs in mixed location (aOR, 3.73; 95% CI, 1.67-8.31). When stratifying by ICH location, incident CMBs were associated in nonlobar ICH with incident lacunes (aOR, 2.86; 95% CI, 1.04-7.85) and with the use of antiplatelet agents (aOR, 2.89; 95% CI, 1.14-7.32). In lobar ICH, incident CMBs were associated with incident radiological macrohemorrhage (aOR, 9.76; 95% CI, 1.07-88.77). CONCLUSIONS: Prognostic and associated factors of incident CMBs differed according to the index ICH location. Whereas in lobar ICH, incident CMBs were associated with hemorrhagic biomarkers, in nonlobar ICH, ischemic burden also increased. CMBs may be interesting biomarkers to monitor in randomized trials on restarting antithrombotic drugs after ICH.

Asunto(s)

Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiología , Microvasos/patología , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos

RESUMEN

OBJECTIVES: To investigate arterial spin-labelling (ASL) cerebral blood flow (CBF) changes in predementia stages of Alzheimer's disease (AD). METHODS: Data were obtained from 177 patients with subjective complaints, mild cognitive impairment and AD from the Amsterdam Dementia Cohort. AD stages were based on diagnosis and cerebrospinal fluid biomarkers amyloid-ß (Aß) and total-tau (tau). General-linear-models were used to assess relationships between AD stages and total and regional CBF, correcting for age and sex. RESULTS: Decreasing CBF was related to more advanced AD stages in all supratentorial regions (p for trend < 0.05). Post-hoc testing revealed that CBF was lower in AD compared to controls and stage-1 predementia patients (i.e. abnormal Aß and normal tau) in temporal and parietal regions, and compared to stage-2 predementia patients (i.e. abnormal Aß and tau) in temporal regions. CBF values of stage-2 predementia patients were numerically in between those of stage-1 predementia patients and AD. CONCLUSION: The continuing decrease of CBF along the continuum of AD indicates the potential of ASL-CBF as a measure for disease progression. KEY POINTS: • Decreasing CBF relates to more advanced AD stages in all supratentorial regions. • The reduction of CBF does not reach a bottom level. • ASL-CBF has potential as a measure for disease progression in AD.

Asunto(s)

Enfermedad de Alzheimer/fisiopatología , Circulación Cerebrovascular/fisiología , Imagen por Resonancia Magnética , Anciano , Enfermedad de Alzheimer/diagnóstico , Estudios de Cohortes , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Marcadores de Spin

RESUMEN

INTRODUCTION: We aimed to investigate if thinner cortex of the Alzheimer's disease (AD)-signature region was related to clinical progression in patients with subjective cognitive decline (SCD). METHODS: We included 302 SCD patients with clinical follow-up (≥1 year) and three-dimensional T1 magnetic resonance imaging. We estimated AD-signature cortical thickness, consisting of nine frontal, parietal, and temporal gyri and hippocampal volume. We used Cox proportional hazard models (hazard ratios and 95% confidence intervals) to evaluate cortical thickness in relation to clinical progression to mild cognitive impairment (MCI) or dementia. RESULTS: After a follow-up of the mean (standard deviation) 3 (2) years, 49 patients (16%) showed clinical progression to MCI (n = 32), AD (n = 9), or non-AD dementia (n = 8). Hippocampal volumes, thinner cortex of the AD-signature (hazard ratio [95% confidence interval], 5 [2-17]) and various AD-signature subcomponents were associated with increased risk of clinical progression. Stratified analyses showed that thinner AD-signature cortex was specifically predictive for clinical progression to dementia but not to MCI. DISCUSSION: In SCD patients, thinner regional cortex is associated with clinical progression to dementia.

RESUMEN

BACKGROUND AND PURPOSE: Stroke and dementia are closely related, but no prospective study ever focused on poststroke cognitive decline in patients with intracerebral hemorrhage (ICH). We aimed to determine prognostic factors for cognitive decline in patients with ICH. METHODS: We prospectively included 167 consecutive ICH survivors without preexisting dementia from the Prognosis of Intra-Cerebral Hemorrhage (PITCH) cohort. Median follow-up was 4 years (interquartile range, 2.3-5.4). We explored factors associated with cognitive decline using linear mixed models. Cognitive decline was determined based on repeated mini-mental state examination. We investigated each prognostic factor separately in univariate models. Next, we constructed clinical and radiological multivariable models. In a sensitivity analysis, we excluded patients with preexisting cognitive impairment. RESULTS: Median age was 64 (interquartile range, 53-75) years, 69 (41%) patients were women, and median mini-mental state examination at 6 months was 27 (interquartile range, 23-29). Overall, 37% of the patients declined during follow-up. Factors associated with cognitive decline in univariate analyses were previous stroke or transient ischemic attack, preexisting cognitive impairment, microbleed presence, severity of white matter hyperintensities, and severity of cortical atrophy. In multivariable analyses, previous stroke or transient ischemic attack (ß [SE], -0.55 [0.23]; P<0.05), preexisting cognitive impairment (ß [SE], -0.56 [0.25]; P<0.01), and severity of cortical atrophy (ß [SE], -0.50 [0.19]; P<0.01) remained independent prognostic factors. In patients without preexisting cognitive impairment (n=139), severity of cortical atrophy (ß [SE], -0.38 [0.17]; P<0.05) was the only prognostic factor for future cognitive decline. CONCLUSIONS: Prognostic factors for cognitive decline after ICH are already present when ICH occurs, suggesting a process of ongoing cognitive impairment instead of new-onset decline induced by the ICH itself.

Asunto(s)

Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/psicología , Trastornos del Conocimiento/etiología , Anciano , Trastornos del Conocimiento/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Pronóstico , Estudios Prospectivos , Tomografía Computarizada por Rayos X

RESUMEN

BACKGROUND AND PURPOSE: In patients with subjective cognitive decline, we assessed whether small vessel disease was associated with clinical progression and cognitive decline. METHODS: We included 334 patients with subjective cognitive decline. Follow-up was 3±2 years. RESULTS: Fifty-three (16%) patients progressed clinically to mild cognitive impairment or dementia. White matter hyperintensities were associated with clinical progression and with annual decline on memory, attention, executive functioning, and global cognition. Microbleeds and lacunes were not associated with clinical progression or cognitive decline. CONCLUSIONS: In patients with subjective cognitive decline, patients with white matter hyperintensities are at increased risk of clinical progression and cognitive decline.

Asunto(s)

Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Demencia/patología , Demencia/fisiopatología , Progresión de la Enfermedad , Sustancia Blanca/patología , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino

RESUMEN

OBJECTIVES: Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [(18)F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. METHODS: Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. RESULTS: Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68). CONCLUSIONS: Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET. KEY POINTS: • Similar patterns of hypoperfusion and hypometabolism were observed in patients with dementia. • For both imaging modalities, parietal abnormalities were found in Alzheimer's disease. • For both imaging modalities, prefrontal abnormalities were found in frontotemporal dementia.

Asunto(s)

Enfermedad de Alzheimer/fisiopatología , Circulación Cerebrovascular/fisiología , Demencia Frontotemporal/fisiopatología , Enfermedad de Alzheimer/metabolismo , Análisis de Varianza , Glucemia/metabolismo , Estudios de Casos y Controles , Femenino , Fluorodesoxiglucosa F18 , Demencia Frontotemporal/metabolismo , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Curva ROC , Radiofármacos , Estudios Retrospectivos , Marcadores de Spin

RESUMEN

IMPORTANCE: Microbleeds are more prevalent in patients with Alzheimer disease (AD) compared with the general elderly population. In addition, microbleeds have been found to predict mortality in AD. OBJECTIVE: To investigate whether microbleeds in AD increase the risk for mortality, stroke (including intracerebral hemorrhage), and cardiovascular events. DESIGN, SETTING AND PARTICIPANTS: The MISTRAL (do MIcrobleeds predict STRoke in ALzheimer's disease) Study is a longitudinal cohort study within the memory clinic-based Amsterdam Dementia Cohort. We selected all patients with AD with a baseline visit between January 2, 2002, and December 16, 2009, and microbleeds (n = 111) and matched those (1:2) for age, sex, and magnetic resonance imaging scanner to 222 patients with AD without microbleeds. After a minimal follow-up of 3 years, information on all-cause mortality, stroke-related mortality, and cardiovascular mortality was obtained between November 1, 2012, and May 1, 2014. In addition, we obtained information on the occurrence of incident stroke or transient ischemic attack, cardiovascular events, and nursing home admittance. MAIN OUTCOMES AND MEASURES: Stroke-related mortality, incident stroke, and intracerebral hemorrhage. RESULTS: Patients had a mean (SD) age of 71.2 (7.8) years and 127 (42%) were female. Compared with having no microbleeds, microbleeds in lobar locations were associated with an increased risk for stroke-related mortality (hazard ratio [HR], 33.9; 95% CI, 2.5-461.7), whereas nonlobar microbleeds were associated with an increased risk for cardiovascular mortality (HR, 12.0; 95% CI, 3.2-44.7). In addition, lobar microbleeds were associated with an increased risk for incident stroke (HR, 3.8; 95% CI, 1.5-10.1) and nonlobar microbleeds with an increased risk for cardiovascular events (HR, 6.2; 95% CI, 1.5-25.0). Even higher risks for incident stroke and cardiovascular events were found in patients using antithrombotic medication. All 5 patients with an intracerebral hemorrhage had lobar microbleeds at baseline; 4 of them used antithrombotics. CONCLUSIONS AND RELEVANCE: In patients with AD, the presence of nonlobar microbleeds was associated with an increased risk for cardiovascular events and cardiovascular mortality. Patients with lobar microbleeds had an increased risk for stroke and stroke-related mortality, indicating that these patients should be treated with the utmost care.

Asunto(s)

Enfermedad de Alzheimer/mortalidad , Enfermedades Cardiovasculares/mortalidad , Hemorragia Cerebral/mortalidad , Ataque Isquémico Transitorio/mortalidad , Accidente Cerebrovascular/mortalidad , Anciano , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/patología , Enfermedades Cardiovasculares/epidemiología , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/patología , Comorbilidad , Femenino , Humanos , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/patología , Estudios Longitudinales , Masculino , Países Bajos/epidemiología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/patología

RESUMEN

OBJECTIVES: To compare pseudo-continuous arterial spin-labelled (PCASL) magnetic resonance imaging (MRI) measured quantitative cerebral blood flow (CBF) of patients with frontotemporal dementia (FTD), dementia with Lewy Bodies (DLB), Alzheimer's disease (AD) and controls, in a region of interest (ROI) and voxel-wise fashion. METHODS: We analysed whole-brain 3D fast-spin-echo PCASL images of 20 FTD patients, 14 DLB patients, 48 AD patients and 50 controls from the Amsterdam Dementia Cohort. Regional CBF patterns were compared using analyses of variance for repeated measures. Permutation tests were used for voxel-wise comparisons. Analyses were performed using uncorrected and partial volume corrected (PVC) maps. All analyses were corrected for age and sex. RESULTS: There was an interaction between diagnosis and region (p < 0.001), implying differences in regional CBF changes between diagnostic groups. In AD patients, CBF was decreased in all supratentorial regions, most prominently so in the posterior regions. DLB patients showed lowest CBF values throughout the brain, but temporal CBF was preserved. Supratentorial PVC cortical CBF values were lowest in the frontal lobes in FTD patients, and in the temporal lobes in AD patients. CONCLUSIONS: Patients with AD, FTD and DLB display distinct patterns of quantitative regional CBF changes. 3D-PCASL may provide additional value in the workup of dementia patients. KEY POINTS: Patterns of regional CBF changes differ between AD, FTD and DLB patients. CBF is lower throughout the brain in DLB than AD and FTD. 3D-PCASL MRI is a potential non-invasive and easily accessible alternative to FDG-PET. 3D-PCASL MRI may be of additional value in the workup of dementia.

Asunto(s)

Enfermedad de Alzheimer/diagnóstico , Imagen Eco-Planar/métodos , Demencia Frontotemporal/diagnóstico , Imagenología Tridimensional/métodos , Cuerpos de Lewy/patología , Enfermedad por Cuerpos de Lewy/diagnóstico , Anciano , Enfermedad de Alzheimer/fisiopatología , Femenino , Estudios de Seguimiento , Lóbulo Frontal/patología , Demencia Frontotemporal/fisiopatología , Humanos , Enfermedad por Cuerpos de Lewy/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Lóbulo Temporal/patología

RESUMEN

To better understand whether decreased cerebral blood flow (CBF) in patients with Alzheimer's disease (AD) reflects neurodegeneration or cerebral small vessel disease, we investigated the associations of normalized brain volume (NBV) and white matter hyperintensity (WMH) volume with CBF. We included 129 patients with AD (66 ± 7 years, 53% female) and 61 age-matched controls (64 ± 5 years, 43% female). CBF was measured with pseudocontinuous arterial spin labeling at 3T in the whole brain and in partial volume corrected cortical maps. When NBV and WMH were simultaneously entered in age and sex adjusted models, smaller NBV was associated with lower whole brain (Stß: 0.29; p < 0.01) and cortical CBF (Stß: 0.28; p < 0.01) in patients with AD. Larger WMH volume was also associated with lower whole brain (Stß: -0.22; p < 0.05) and cortical CBF (Stß: -0.24; p < 0.05) in AD. Additional adjustments did not change these results. In controls, neither NBV nor WMH was associated with CBF. Our results indicate that in AD, lower CBF as measured using pseudocontinuous arterial spin labeling, reflects the combined disease burden of both neurodegeneration and small vessel disease.

Asunto(s)

Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Encéfalo/irrigación sanguínea , Encéfalo/patología , Circulación Cerebrovascular , Sustancia Blanca/patología , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos

RESUMEN

IMPORTANCE: It remains unclear if and how associations between cerebral small-vessel disease and Alzheimer disease (AD) pathology lead to cognitive decline and dementia. OBJECTIVE: To determine associations between small-vessel disease and AD pathology. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study from January 2002 to December 2012 using the memory clinic-based Amsterdam Dementia Cohort. The study included 914 consecutive patients with available cerebrospinal fluid (CSF) and magnetic resonance imaging; 547 were patients diagnosed as having AD (54% female, mean [SD], 67 [8]; Mini-Mental State Examination score, mean [SD], 21 [5]), 30 were patients diagnosed as having vascular dementia (37% female, mean [SD], 76 [9]; Mini-Mental State Examination score, mean [SD], 24 [4]), and 337 were control participants with subjective memory complaints (42% female, mean [SD], 59 [59]; Mini-Mental State Examination score, mean [SD], 28 [2]). Linear regressions were performed with CSF biomarkers (log transformed) as dependent variables and magnetic resonance imaging measures (dichotomized) as independent, adjusted for sex, age, mediotemporal lobe atrophy, and diagnosis. An interaction term for diagnosis by magnetic resonance imaging measures was used for estimates per diagnostic group. MAIN OUTCOMES AND MEASURES: We examined the associations of magnetic resonance imaging white matter hyperintensities (WMH), lacunes, microbleeds with CSF ß-amyloid 42 (Aß42), total tau, and tau phosphorylated at threonine 181 (P-tau181) as well as for a subset of apolipoprotein E (APOE) ε4 carriers and noncarriers. RESULTS: Microbleed presence was associated with lower CSF Aß42 in AD and vascular dementia (standardized beta = -0.09, P = .003; standardized beta = -0.30, P = .01), and higher CSF tau in controls (standardized beta = 0.10, P = .03). There were no effects for P-tau181. The presence of WMH was associated with lower Aß42 in control participants and patients with vascular dementia (standardized beta = -0.18, P = .002; standardized beta = -0.32, P = .02) but not in patients with AD. There were no effects for tau or P-tau181. The presence of lacunes was associated with higher Aß42 in vascular dementia (standardized beta = 0.17, P = .07) and lower tau in AD (standardized beta = -0.07, P = .05) but there were no effects for Aß42 or P-tau181. Stratification for apolipoprotein E genotype revealed that these effects were mostly attributable to ε4 carriers. CONCLUSIONS AND RELEVANCE: Deposition of amyloid appears aggravated in patients with cerebral small-vessel disease, especially in apolipoprotein E ε4 carriers, providing evidence for pathophysiological synergy between these 3 biological factors.

Asunto(s)

Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/patología , Enfermedades de los Pequeños Vasos Cerebrales/líquido cefalorraquídeo , Enfermedades de los Pequeños Vasos Cerebrales/patología , Anciano , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/metabolismo , Apolipoproteína E4/líquido cefalorraquídeo , Apolipoproteína E4/metabolismo , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/metabolismo , Estudios Transversales , Femenino , Tamización de Portadores Genéticos , Hemorragia/sangre , Hemorragia/líquido cefalorraquídeo , Hemorragia/patología , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/metabolismo , Fosforilación , Accidente Vascular Cerebral Lacunar/sangre , Accidente Vascular Cerebral Lacunar/líquido cefalorraquídeo , Accidente Vascular Cerebral Lacunar/patología , Proteínas tau/líquido cefalorraquídeo , Proteínas tau/metabolismo

RESUMEN

OBJECTIVES: Validate the four-point visual rating scale for posterior cortical atrophy (PCA) on magnetic resonance images (MRI) through quantitative grey matter (GM) volumetry and voxel-based morphometry (VBM) to justify its use in clinical practice. METHODS: Two hundred twenty-nine patients with probable Alzheimer's disease and 128 with subjective memory complaints underwent 3T MRI. PCA was rated according to the visual rating scale. GM volumes of six posterior structures and the total posterior region were extracted using IBASPM and compared among PCA groups. To determine which anatomical regions contributed most to the visual scores, we used binary logistic regression. VBM compared local GM density among groups. RESULTS: Patients were categorised according to their PCA scores: PCA-0 (n = 122), PCA-1 (n = 143), PCA-2 (n = 79), and PCA-3 (n = 13). All structures except the posterior cingulate differed significantly among groups. The inferior parietal gyrus volume discriminated the most between rating scale levels. VBM showed that PCA-1 had a lower GM volume than PCA-0 in the parietal region and other brain regions, whereas between PCA-1 and PCA-2/3 GM atrophy was mostly restricted to posterior regions. CONCLUSIONS: The visual PCA rating scale is quantitatively validated and reliably reflects GM atrophy in parietal regions, making it a valuable tool for the daily radiological assessment of dementia. KEY POINTS: • Visual rating scale reflects grey matter atrophy in posterior brain regions. • Different PCA scores corresponded well to different quantitative degrees of atrophy. • Inferior parietal gyrus volume influenced assessment based on the visual rating scale. • This simple visual rating scale makes it useful for radiological dementia assessment.

Asunto(s)

Enfermedad de Alzheimer/diagnóstico , Corteza Cerebral/patología , Imagen por Resonancia Magnética/métodos , Lóbulo Parietal/patología , Anciano , Atrofia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos