White Matter Lesions on Brain Magnetic Resonance Imaging Scan and 5‐Year Cognitive Decline: The Honolulu‐Asia Aging Study

Inaba, Michiko; White, Lon R.; Bell, Christina; Chen, Randi; Petrovitch, Helen; Launer, Lenore J.; Abbott, Robert D.; Ross, G. Webster; Masaki, Kamal

doi:10.1111/j.1532-5415.2011.03490.x

Cited by 45 publications

(38 citation statements)

References 28 publications

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“…First, only the most common neuropathologic indices were included in the analysis. Other age-related neuropathologies such as TDP-43 (Tremblay et al 2011), hippocampal sclerosis (Corey-Bloom et al 1997, Nelson et al 2012), and white matter lesions (Inaba et al 2011) have been shown to be associated with cognitive impairment and AD. We do not yet have sufficient data to fully incorporate these disease markers in our analysis.…”

Section: Discussionmentioning

confidence: 99%

Disentangling the effects of age and APOE on neuropathology and late life cognitive decline

Boyle

Leurgans

et al. 2014

Neurobiology of Aging

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Age and APOE are the most robust risk factors for dementia and cognitive decline, but the underlying neurobiology remains unclear. We examined the extent to which the hallmark pathologies of Alzheimer’s disease, Lewy body disease, and cerebrovascular diseases account for the association of age and APOE with decline in episodic memory versus non-episodic cognitive abilities. Up to 20 waves of longitudinal cognitive data were collected from 858 autopsied participants in two ongoing clinical-pathologic cohort studies of aging. Neuropathologic examinations quantified measures of beta amyloid plaque (Aβ), mesial temporal and neocortical neurofibrillary tangles, macro- and microinfarcts, and neocortical Lewy bodies. Random coefficient models estimated person-specific slopes of decline in episodic memory and non-episodic cognition. Path analysis examined the relation of age, APOE and the six pathologic indices to the slopes of cognitive decline. The effect of age on decline in episodic memory was mediated by Aβ, mesial temporal and neocortical tau tangles, as well as macroscopic infarcts; age on decline in non-episodic cognition was mediated by Aβ, neocortical tangles, and macroscopic infarcts. The effect of APOE on decline in episodic memory was mediated by Aβ, mesial temporal and neocortical tangles, as well as neocortical Lewy bodies; APOE on non-episodic cognition was mediated by Aβ, neocortical tangles and neocortical Lewy bodies. There were no direct effects of age and APOE on decline after accounting for these pathologic pathways.

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Section: Discussionmentioning

confidence: 99%

Disentangling the effects of age and APOE on neuropathology and late life cognitive decline

Boyle

Leurgans

et al. 2014

Neurobiology of Aging

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“…10,19,31,32 These discrepancies may relate to the fact that none of the women of the KEEPS-MRI study had uncontrolled hypertension, their BMI was ,30 kg/mm 2 , and fasting glucose was within the normative range.…”

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confidence: 92%

“…It is noteworthy that the relationship between WMH and platelet-derived microvesicles in the peripheral circulation was only significant with data adjusted for age, because age is associated with increased WMH load in older women. 2,32 Moreover, the observed variability in changes of WMH load in the KEEPS-MRI study population may be the result of biological variability and hormonal effects of treatment that could not be analyzed because of blinding to treatment randomization. An activated intravascular compartment may lead to a cascade of events that predicate development of arterial lesions in the periphery with subsequent damage to the heart or kidneys.…”

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confidence: 99%

Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women

et al. 2013

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Objective: To determine the association of conventional cardiovascular risk factors, markers of platelet activation, and thrombogenic blood-borne microvesicles with white matter hyperintensity (WMH) load and progression in recently menopausal women.Methods: Women (n 5 95) enrolled in the Mayo Clinic Kronos Early Estrogen Prevention Study underwent MRI at baseline and at 18, 36, and 48 months after randomization to hormone treatments. Conventional cardiovascular risk factors, carotid intima-medial thickness, coronary arterial calcification, plasma lipids, markers of platelet activation, and thrombogenic microvesicles were measured at baseline. WMH volumes were calculated using a semiautomated segmentation algorithm based on fluid-attenuated inversion recovery MRI. Correlations of those parameters with baseline WMH and longitudinal change in WMH were adjusted for age, months past menopause, and APOE e4 status in linear regression analysis.Results: At baseline, WMH were present in all women. The WMH to white matter volume fraction at baseline was 0.88% (0.69%, 1.16%). WMH volume increased by 122.1 mm 3 (95% confidence interval: 2164.3, 539.5) at 36 months (p 5 0.003) and 155.4 mm 3 (95% confidence interval: 292.13, 599.4) at 48 months (p , 0.001). These increases correlated with numbers of platelet-derived and total thrombogenic microvesicles at baseline (p 5 0.03). White matter hyperintensities (WMH) observed in the aging brain are associated with small-vessel disease. Conclusion:1,2 Although high WMH load may lead to mild cognitive impairment 3-6 and increase the risk of stroke, 7,8 little is known regarding the source or nature of cellular factors mediating their formation. 9Conventional cardiovascular risk factors such as hypertension, increasing age, smoking, hypercholesterolemia, and a history of cerebrovascular disease are the most consistent risk factors for the load and progression of WMH in elderly persons. 2,[10][11][12] In addition, thrombogenic risk factors including activated cell-derived microvesicles may contribute to formation of WMH, ischemic brain disease, and cognitive decline. [13][14][15][16] In recently menopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS), numbers of platelet-derived and thrombogenic (annexin V-positive) microvesicles correlated with carotid artery intima-medial thickness (CIMT). 17,18 Furthermore, CIMT correlated positively with the prevalence of WMH and poor cognitive performance. 19 Taken together, these studies suggest that cardiovascular risk factors, which may activate platelets to shed thrombogenic microvesicles, affect brain microstructure.

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“…White matter lesions on brain MRI have been known to be associated with functional decline as well as neurodevelopmental impairment, such as severe psychomotor delay, cerebral palsy, and impaired working memory [Woodward et al, 2005[Woodward et al, , 2006Inzitari et al, 2007;Inaba et al, 2011], because cognitive function relies on processing speed and widely distributed neural networks [Gunning-Dixon and Raz, 2000].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, brain MRI allows physicians to detect abnormalities of the central nervous system (CNS) that may adversely affect neurological development as well as cognitive function [Bouhadiba et al, 2000;Hart et al, 2008]. For example, white matter lesions in the brain can be easily detected as high-intensity lesions on proton density and T2-weighted MRI scans [Inaba et al, 2011]. Therefore, in many institutions, preoperative brain MRI is routinely performed before CI, not only to evaluate the status of the inner ear and cochlear nerve, but also to screen for CNS disorders.…”

mentioning

confidence: 99%

The Clinical Significance of Preoperative Brain Magnetic Resonance Imaging in Pediatric Cochlear Implant Recipients

Moon¹,

Kim²,

Park³

et al. 2012

Audiol Neurotol

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Although central nervous system abnormalities are incidentally detected in preoperative brain magnetic resonance imaging (MRI) studies in pediatric cochlear implant (CI) candidates, the clinical significance of the abnormalities remains unclear. We aimed to assess post-implantation auditory and speech performance in patients with brain lesions seen on MRI. Pediatric CI recipients (n = 177) who underwent preoperative MRI scans of the brain between January 2002 and June 2009 were included in this study. Patients with brain lesions on MRI were reviewed and categorized into the following groups: brain parenchymal lesions (focal vs. diffuse), ventriculomegaly, and extra-axial lesion. The main communication mode as well as progress in auditory perception and speech production were evaluated preoperatively and at 3, 6, 12, and 24 months postoperatively. Performance in patients with brain lesions was compared with the age- and sex-matched control group. Various brain lesions were found in 27 out of 177 patients. Children with brain lesions who received CIs showed gradual progress in auditory and speech outcomes for 2 years, though performance was reduced compared with the control group. In addition, there was a significant difference in the main communication mode between the two groups at 2 years following cochlear implantation. This difference was especially significant in patients with diffuse brain parenchymal lesions after further stratification of the brain lesion group. Preoperative brain MRI may have a role in improving the prediction of adverse outcomes in pediatric CI recipients. In particular, children with diffuse brain parenchymal lesions should be counseled regarding the poor prognosis preoperatively, and followed up with special attention.

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White Matter Lesions on Brain Magnetic Resonance Imaging Scan and 5‐Year Cognitive Decline: The Honolulu‐Asia Aging Study

Cited by 45 publications

References 28 publications

Disentangling the effects of age and APOE on neuropathology and late life cognitive decline

Disentangling the effects of age and APOE on neuropathology and late life cognitive decline

Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women

The Clinical Significance of Preoperative Brain Magnetic Resonance Imaging in Pediatric Cochlear Implant Recipients

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