Association of White Matter Hyperintensities with Low Serum 25-Hydroxyvitamin D Levels

Prager, Jordan M.; Thomas, Chinnamma; Ankenbrandt, William; Meyer, Jacob; Gao, Yuanzhu; Ragin, Ann B.; Sidharthan, Sreetha; Hutten, Ryan; Wu, Ying

doi:10.3174/ajnr.a3840

Cited by 19 publications

(25 citation statements)

References 30 publications

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“…9 Another study recently reported an association between WMH and low 25(OH)D in independent outpatients. 10 The current study indicates that hypovitaminosis D is a predictor of WMH in individuals with AD or aMCI. WMH has been found to have clinical relevance in cognitive decline and several geriatric syndrome conditions, 1,2 and vitamin D plays central roles in muscle weakness and physical frailty in elderly individuals.…”

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confidence: 55%

Lower Vitamin D Is Associated with White Matter Hyperintensity in Elderly Women with Alzheimer's Disease and Amnestic Mild Cognitive Impairment

Sakurai

Ogama

Toba

2014

J American Geriatrics Society

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White matter hyperintensity (WMH) on brain magnetic resonance imaging (MRI) is prevalent in the aging brain and is associated with cognitive decline and mobility impairment. 1,2 It is a clinical challenge to establish a prevention strategy for WMH. Although believed to be of vascular origin, the exact etiology of WMH remains unclear. Age and hypertension are consistent risk factors for WMH. High homocysteine levels, diabetes mellitus, hyperlipidemia, smoking, obesity, low vitamin B12 levels, and alcohol consumption are likely to increase WMH. 3 There is growing evidence of potential roles of vitamin D in sustaining healthy brain function. 4 Low serum vitamin D has been reported in Alzheimer's disease (AD), which is often associated with WMH, 5 but little is known about the link between vitamin D and WMH in elderly adults with AD. This study aimed to clarify the interaction between vitamin D, WMH, brain atrophy in elderly adults with AD and amnestic mild cognitive impairment (aMCI).Two hundred fifty-three women aged 65 and older diagnosed with aMCI (n = 39) or AD (n = 214) were recruited. AD was diagnosed as possible or probable AD according the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and aMCI was diagnosed based on previously defined criteria. 2,6 Individuals with severe cardiac failure, renal disorder, liver dysfunction, or musculoskeletal disease or with cortical lesions on MRI were excluded.Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Hypertension, diabetes mellitus, lipid abnormalities, and chronic kidney disease were defined as having a history of these diseases or use of medication to treat them. Information on current smoking and drinking habits was obtained from clinical charts. Vitamin D insufficiency was assessed according to serum concentration of 25-hydroxyvitamin D (25(OH)D).A standard series of axial T2-weighted (repetition time (TR), 3,800 ms; echo time (TE), 93 ms) and fluid-attenuated inversion recovery (TR, 8,000 ms; TE, 101 ms; inversion time, 2,500 ms; a 256 9 256 matrix) MR sequences were obtained using a 1.5-T MR scanner (Siemens Avanto, Munich, Germany). Scans in parallel with the anterior commissure-posterior commissure line were performed with 6-mm-thick slices and an interslice gap of 1.2 mm. 2 MRI data were processed to measure the total volume of the intracranial space (IC), parenchyma, ventricles, and WMH using a fully automatic segmentation program (Software for Neuro-Image Processing in Experimental Research). 7 Statistical analysis was performed using SPSS 19.0 for Windows (SPSS, Inc., Chicago, IL). Because WMH were not normally distributed, their values were converted to rank variables. The association between WMH and clinical variables was analyzed using partial Spearman rank order correlation analysis and multivariate regression (stepwise). Differences were considered significant at P < .05. Table 1 shows the demographic characteris...

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mentioning

confidence: 55%

Lower Vitamin D Is Associated with White Matter Hyperintensity in Elderly Women with Alzheimer's Disease and Amnestic Mild Cognitive Impairment

Sakurai

Ogama

Toba

2014

J American Geriatrics Society

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“…These findings are in contrast with the majority of cross-sectional neuroimaging studies, which have largely found consistent associations between lower vitamin D concentrations and an increased risk of cerebrovascular and neurodegenerative abnormalities. Six cross-sectional studies found that low vitamin D concentrations were significantly associated with more white matter abnormalities [ 4 , 10 , 12 , 13 , 15 , 17 ], although three studies found no association with white matter abnormalities or volume [ 6 , 8 , 19 ]. Whilst, one study found that vitamin D deficiency (≤50 nmol/L) was associated with a 28% increase in lateral ventricle volume compared to those with vitamin D sufficiency (>50 nmol/L) [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cross-sectional studies have consistently found that lower vitamin D concentrations are associated with an increased risk of neuroimaging abnormalities [ 4 – 19 ]. These include cerebrovascular and neurodegenerative pathologies implicated in the development of dementia, such as white matter hyperintensities [ 4 , 10 , 12 , 13 , 15 ], enlarged ventricular volume [ 8 ], large vessel infarcts [ 4 ] and lacunar infarcts [ 15 ]. However, the temporal association cannot be inferred from cross-sectional studies.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D and Risk of Neuroimaging Abnormalities

et al. 2016

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Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer’s disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992–93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991–1994 and the second MRI scan was conducted between 1997–1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25–50 nmol/L) were 0.76 (0.35–1.66) and 1.09 (0.76–1.55) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20–1.19) and 1.12 (0.79–1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84–4.54) and 0.73 (0.47–1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with the development of cerebrovascular or neurodegenerative neuroimaging abnormalities in Cardiovascular Health Study participants.

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“…Several studies have shown the association between WMH and blood levels of molecules, such as cystatin C (CysC), 25‐hydroxyvitamin D and homocysteine, and the presence of lifestyle‐associated diseases, such as hypertension, hyperlipidemia and diabetes mellitus . However, most of these studies have assessed WMH by visual rating, which is not very precise .…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have shown the association between WMH and blood levels of molecules, such as cystatin C (CysC), 25-hydroxyvitamin D and homocysteine, and the presence of lifestyleassociated diseases, such as hypertension, hyperlipidemia and diabetes mellitus. [8][9][10] However, most of these studies have assessed WMH by visual rating, which is not very precise. [3][4][5] In the present study, we calculated the volume of periventricular hyperintensities (PVH) and deep WMH (DWMH) on T2 fluid-attenuated inversion recovery (FLAIR) MRI using 3D Slicer, a freely available, opensource software package for visualization, registration, segmentation, and quantification of medical data (http://www.slicer.org).…”

Section: Introductionmentioning

confidence: 99%

Association of serum cystatin C with white matter abnormalities in patients with amnestic mild cognitive impairment

Hirao

Yamashita

Tsugawa

et al. 2019

Geriatrics Gerontology Int

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AimWhite matter hyperintensities (WMH) on MRI have been reported to be a risk factor for the conversion from mild cognitive impairment (MCI) to Alzheimer's disease, although the reason remains unclear. In the present study, we hence investigated the associations between WMH volumes and cognitive function, blood levels of various molecules, and the presence of lifestyle‐associated diseases in patients with amnestic MCI.MethodsThe initial data of 38 patients with amnestic MCI and 10 normal control individuals were analyzed. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on T2 fluid‐attenuated inversion recovery using the imaging software, 3D Slicer; and the association between PVH/DWMH volumes and cognitive function, blood levels of molecules (such as cystatin C [CysC], 25‐hydroxyvitamin D and homocysteine) and the presence of lifestyle‐associated diseases (such as hypertension, hyperlipidemia and diabetes mellitus) were analyzed.ResultsIn the MCI group, the PVH volume : intracranial volume ratio significantly correlated with Trail Making Test‐A/B scores and CysC level by Pearson's analysis, and the PVH volume : intracranial volume ratio significantly correlated with only CysC levels, whereas the DWMH volume : intracranial volume ratio did not correlate with any items at all by linear multiple regression analysis.ConclusionsPVH volume was closely associated with frontal lobe dysfunction, particularly with attention and executive dysfunction. Serum CysC level was associated with PVH volume, which suggests that CysC might be a useful marker for determining treatment strategies for white matter abnormalities in amnestic MCI. Geriatr Gerontol Int 2019; 19: 1036–1040.

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Association of White Matter Hyperintensities with Low Serum 25-Hydroxyvitamin D Levels

Abstract: BACKGROUND AND PURPOSE:Vitamin D deficiency is associated with cognitive impairment in the elderly and with increased white matter T2 hyperintensities in elderly debilitated patients. We investigated the relationship between serum vitamin D and brain MR findings in adult outpatients.

Cited by 19 publications

References 30 publications

Lower Vitamin D Is Associated with White Matter Hyperintensity in Elderly Women with Alzheimer's Disease and Amnestic Mild Cognitive Impairment

Lower Vitamin D Is Associated with White Matter Hyperintensity in Elderly Women with Alzheimer's Disease and Amnestic Mild Cognitive Impairment

Vitamin D and Risk of Neuroimaging Abnormalities

Association of serum cystatin C with white matter abnormalities in patients with amnestic mild cognitive impairment

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