White matter changes and diabetes predict cognitive decline in the elderly

Verdelho, Ana; Madureira, Sofia; Moleiro, Carla; Ferro, José M.; Santos, Catarina; Erkinjuntti, Timo; Pantoni, Leonardo; Fazekas, Franz; Visser, Marieke C.; Waldemar, Gunhild; Wallin, Anders; Hennerici, Michael G.; Inzitari, Domenico

doi:10.1212/wnl.0b013e3181e7ca05

Cited by 174 publications

(135 citation statements)

References 38 publications

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“…WML burden has been associated with decreased capacity for gross motor function such as gait, as well as visuo-psychomotor function, in people older than 65 years. 6,[26][27][28] However, this is the first study to suggest that in a higher-risk population, the associations exist at much younger ages.…”

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confidence: 70%

Effect of white matter lesions on manual dexterity in healthy middle-aged persons

et al. 2015

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Objectives: We hypothesized that integrated motor-visual functions measured by manipulative manual dexterity are affected by white matter lesion (WML) burden as measured on cranial MRI across relevant brain regions in subjects at risk of preclinical occult vascular disease.Methods: A real-time cross-sectional study of healthy subjects aged 29 to 74 years with a family history of early-onset coronary artery disease (n 5 714; mean age, 51 6 11 years; mean education, 14 6 3 years; 42% male; 38% black) were identified from probands with coronary artery disease diagnosed before age 60 years. WMLs on 3-tesla brain MRI and Grooved Pegboard scores were measured.Results: WMLs were observed at all ages. Mean pegboard scores were 108 6 18, similar to normal populations. In unadjusted analysis, WMLs and pegboard scores were significantly correlated by region (total WMLs, r 5 0. . In multivariate analysis predicting (log) pegboard score adjusted for age, sex, race, education, regional or total volumes, and familial nonindependence, total WML volume (p 5 5.79E 2 05) and regional WML volumes (p , 0.01) retained statistical significance in all but the youngest age quartile (29-43 years).Conclusions: Greater WML volumes in different brain regions are associated with higher pegboard scores (worse performance) independent of age, sex, race, education, and total or regional volumes. This suggests that small vessel cerebrovascular disease may be present in healthy individuals in a preclinical state with measurable impact on complex integrative functions in individuals with excess risk of clinical vascular disease. Neurology ® 2015;84:1920-1926 GLOSSARY CAD 5 coronary artery disease; FLAIR 5 fluid-attenuated inversion recovery; MMSE 5 Mini-Mental State Examination; MPRAGE 5 magnetization-prepared rapid-gradient echo; TOADS 5 topology-preserving anatomy-driven segmentation; WML 5 white matter lesion.White matter lesions (WMLs) appearing as hyperintense regions on fluid-attenuated inversion recovery (FLAIR) and T2 MRIs are thought to be caused by small vessel cerebrovascular disease.1 WML volume and number are associated with age and are most notable in older age groups.1,2 Overall, WML burden is an independent predictor of clinical dementia and of decrements in motor function, including gait, psychomotor speed, and motor apraxia. [3][4][5][6] We have published data that show a high prevalence of occult coronary artery disease (CAD) and cerebral small vessel lesions in younger and middle-aged people from families with a history of early-onset CAD.7-9 High-risk individuals may also be at increased risk of functional consequences of occult small vessel cerebrovascular disease. 9 To date, most studies of WMLs have addressed older populations and persons with cognitive functional decline or clinical dementia. 2The Northern Manhattan Study, which was conducted in a healthy community population, found that patients with a WML volumetric threshold at the 75th percentile performed

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confidence: 70%

Effect of white matter lesions on manual dexterity in healthy middle-aged persons

et al. 2015

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“…We examined the potential mediating role of changes in ventricular size or WMH on cognitive decline, since both cerebral atrophy 35,36 and WMH severity 37 and progression 38,39 have been associated with decreases in cognition. Our results suggest that increased ventricular size (a marker of cerebral atrophy), but not changes in WMH, may mediate a portion of decline in DSST scores, although it appears that a large portion of cognitive change occurs independent of structural changes observable on brain MRI.…”

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confidence: 99%

Association of hospitalization with long-term cognitive and brain MRI changes in the ARIC cohort

et al. 2015

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Objective: To determine whether hospitalization is associated with subsequent cognitive decline or changes on brain MRI in a community-based cohort.Methods: Baseline and follow-up cognitive testing (n 5 2,386) and MRI scans with standardized assessments (n 5 885) were available from a subset of white and black participants in the Atherosclerosis Risk in Communities study. Cognitive tests included the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). Hospitalization characteristics were determined using ICD-9 codes. Regression models adjusted for demographics, education, comorbidities, and APOE e4 were used to estimate the independent association of hospitalization with changes in cognition or neuroimaging.Results: Over a mean 14.1 years between visits, 1,266 participants (53.1%) were hospitalized.Hospitalization compared with no hospitalization was associated with greater decline in DSST scores (1.25 points greater decline, p , 0.001) but no difference in DWRT or WFT score change. Each additional hospitalization, as well as a critical illness vs noncritical illness hospitalization, was associated with greater decline in DSST scores. A subset of participants (n 5 885) underwent MRI scans separated by 10.5 years. Hospitalization (n 5 392) compared with no hospitalization was associated with a 57% higher odds of increasing ventricular size at follow-up. Each additional hospitalization, as well as having a critical illness vs noncritical illness hospitalization, and having a hospitalization with major surgery vs no surgery was associated with greater odds of increased ventricular size. Hospitalizations in older adults (.65 years) account for more than one third of community hospital stays and result in substantial morbidity and mortality. [1][2][3] Recently, evidence has emerged that hospitalization may be associated with long-term cognitive decline and incident dementia, even in the absence of hospitalization for stroke or head trauma. [4][5][6] However, the association between hospitalization and cognitive decline has not been well-characterized, although establishing the magnitude and etiology of cognitive decline would be crucial to develop targeted prevention strategies. Conclusions:In order to characterize the independent associations of hospitalization with cognitive change, accurate assessment of a patient's prehospitalization comorbidities is critical, since hospitalization might only be a marker of vulnerability. However, previous studies have been limited by excessive reliance on patient self-reported comorbidities, which may lead to misclassification with residual confounding, and lack of accounting for APOE e4 status. The potential

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“…[3][4][5] WMD has gained growing interest, because it may play a role in cognitive decline and as a risk factor for first and recurrent ischemic stroke and death. [6][7][8][9] The pathophysiology of WMD is not completely understood, and several etiologic mechanisms are discussed. The majority of research and experimental findings suggest chronic ischemic pathogenesis in the development and progression of WMD.…”

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confidence: 99%

Elevated Levels of Hemoglobin A1c Are Associated With Cerebral White Matter Disease in Patients With Stroke

Różański

Richter

Grittner³

et al. 2014

Stroke

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Background and Purpose-This study was conducted to investigate the association of cerebral white matter disease (WMD) on MRI with vascular risk factors and laboratory findings in consecutive first acute ischemic stroke patients. Methods-Acute ischemic stroke patients underwent MRI ≤24 hours after stroke onset and follow-up on day 2. WMD was scored on fluid attenuated inversion recovery MRI according to the Wahlund score.

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White matter changes and diabetes predict cognitive decline in the elderly

Abstract: WMC severity and diabetes are independent predictors of cognitive decline in an initially nondisabled elderly population. Vascular dementia is predicted by previous stroke and WMC, while AD is predicted only by MTA.

Cited by 174 publications

References 38 publications

Effect of white matter lesions on manual dexterity in healthy middle-aged persons

Effect of white matter lesions on manual dexterity in healthy middle-aged persons

Association of hospitalization with long-term cognitive and brain MRI changes in the ARIC cohort

Elevated Levels of Hemoglobin A1c Are Associated With Cerebral White Matter Disease in Patients With Stroke

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