Periventricular white matter hyperintensities and the risk of dementia: a CREDOS study

Kim, Sang-Ha; Choi, Seong Hye; Lee, Young Min; Kim, Min Ji; Kim, Young Don; Kim, Jin Young; Park, Jin‐Hong; Myung, Woojae; Na, Hae Ri; Han, Hyun Jeong; Shim, Yong S.; Kim, Jong Hun; Yoon, Soo Jin; Kim, SangYun; Kim, Doh Kwan

doi:10.1017/s1041610215001076

Cited by 63 publications

(66 citation statements)

References 35 publications

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“…Change in ADAS13 scores (indicating worsening cognitive performance) was significantly associated with baseline WMH load, GM volume, Aβ levels, and presence of one or two APOE alleles (Figure 4). These findings are also in line with previous studies reporting an impact of WMH burden [3][4][5][6]8,7] and GM atrophy on cognitive performance/decline [31,32]. However, those studies had not assessed the impact of WMHs and GM atrophy simultaneously.…”

Section: Resultssupporting

confidence: 91%

“…Pathologically, WMHs have been associated with gliosis, demyelination, axonal loss, arteriosclerosis due to hypoxia, hypoperfusion, blood-brain barrier leakage, inflammation, degeneration, and amyloid angiopathy [2]. Clinically, WMHs have been associated with increased risks of cognitive decline in otherwise normal aging (NA), individuals with mild cognitive impairment (MCI), and patients with probable Alzheimer's disease (AD) [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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The Temporal Relationships between White Matter Hyperintensities, Neurodegeneration, Amyloid β, and Cognition

Dadar

Camicioli

Duchesne

et al. 2020

Preprint

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INTRODUCTION:Cognitive decline in Alzheimer's disease is associated with amyloid-β accumulation, neurodegeneration and cerebral small vessel disease, but the temporal relationships between these factors is not well established. METHODS:Data included white matter hyperintensity (WMH) load, grey matter (GM) atrophy and Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS13) scores for 720 participants and cerebrospinal fluid amyloid (Aβ1-42) for 461 participants from the Alzheimer's Disease Neuroimaging Initiative. Linear regressions were used to assess the relationships between baseline WMH, GM, and Aβ1-42 to changes in WMH, GM, Aβ1-42, and cognition at one-year follow-up. RESULTS: Baseline WMHs and Aβ1-42 predicted WMH increase and GM atrophy. Baseline WMHs, GM, and Aβ1-42 predicted worsening cognition. Only baseline Aβ1-42 predicted change in Aβ1-42. DISCUSSION: Baseline WMHs lead to greater future GM atrophy and cognitive decline, suggesting that WM damage precedes neurodegeneration and cognitive decline. Baseline Aβ1-42 predicted WMH increase, suggesting a potential role of amyloid in WM damage. Keywords: White matter hyperintensities, small-vessel disease, neurodegenerative disease, Alzheimer's disease, mild cognitive impairment Research in Context 1. Systematic Review: Both amyloid β and neurodegeneration are primary pathologies in Alzheimer's disease. White matter hyperintensities (indicative of presence of cerebrovascular disease) might also be part of the pathological changes in Alzheimer's. However, the temporal relationship between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline is still unclear. Interpretation:Our results establish a potential temporal order between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline, showing that white matter hyperintensities precede neurodegeneration and cognitive decline. The results provide some evidence that amyloid β deposition, in turn, precedes accumulation of white matter hyperintensities. Future Directions:The current findings reinforce the need for future longitudinal investigations of the mechanisms through which white matter hyperintensities impact the aging population in general and Alzheimer's disease patients, in particular.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

The Temporal Relationships between White Matter Hyperintensities, Neurodegeneration, Amyloid β, and Cognition

Dadar

Camicioli

Duchesne

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Overall, the available evidence highlights some variability in conversion rates from MCI to dementia, ranging from about 15 to 50% [ 23 , 24 , 25 , 26 , 27 , 28 ]. Several factors, such as the follow-up duration (ranging from 2 to 5 years) and the diagnostic criteria [ 23 , 24 , 25 , 26 , 27 , 28 ], likely explain this variability. The conversion rate in our short-term follow-up study was similar to that found in other studies with similar follow-up durations [ 24 , 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Application of the DSM-5 Criteria for Major Neurocognitive Disorder to Vascular MCI Patients

Salvadori

Poggesi

Pracucci

et al. 2018

Dement Geriatr Cogn Disord Extra

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Aims: The DSM-5 introduced the term “major neurocognitive disorders” (NCDs) to replace the previous term “dementia.” However, psychometric and functional definitions of NCDs are missing. We aimed to apply the DSM-5 criteria for diagnosing the transition to NCD to patients with mild cognitive impairment (MCI) and small vessel disease (SVD), and to define clinically significant thresholds for this transition. Methods: The functional and cognitive features of the NCD criteria were evaluated as change from baseline and operationalized according to hierarchically ordered psychometric rules. Results: According to the applied criteria, out of 138 patients, 44 were diagnosed with major NCD (21 with significant cognitive worsening in ≥1 additional cognitive domain), 84 remained stable, and 10 reverted to normal. Single-domain MCI patients were the most likely to revert to normal, and none progressed to major NCD. The amnestic multiple-domain MCI patients had the highest rate of progression to NCD. Conclusion: We provide rules for the DSM-5 criteria for major NCD based on cognitive and functional changes over time, and define psychometric thresholds for clinically significant worsening to be used in longitudinal studies. According to these operationalized criteria, one-third of the MCI patients with SVD progressed to major NCD after 2 years, but only within the multiple-domain subtypes.

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“…Greater WMH is related to rapid cognitive decline in MCI subjects (Tosto et al, 2014 ). Furthermore, severe WMH also predicts the progression from MCI to dementia (Prasad et al, 2011 ; Kim et al, 2015 ). The divergences may be due to two reasons.…”

Section: Discussionmentioning

confidence: 99%

Divergent Roles of Vascular Burden and Neurodegeneration in the Cognitive Decline of Geriatric Depression Patients and Mild Cognitive Impairment Patients

Gong

et al. 2017

Front. Aging Neurosci.

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Both geriatric depression and mild cognitive impairment (MCI) confer an increased risk for the development of dementia. The mechanisms underlying the development of cognitive impairment in geriatric depression patients remain controversial. The present study aimed to explore the association of cognitive decline with vascular risk, white matter hyperintensity (WMH) burden and hippocampal volume in both remitted geriatric depression (RGD) subjects and amnestic mild cognitive impairment (aMCI) subjects. Forty-one RGD subjects, 51 aMCI subjects, and 64 healthy elderly subjects underwent multimodal MRI scans and neuropsychological tests at both baseline and a 35-month follow-up. According to the changing patterns (declining or stable) of global cognitive function during the follow-up period, each group was further divided into a declining subgroup and a stable subgroup. The Framingham 10-year cardiovascular risk, WMH volume and hippocampal volume were measured to assess vascular pathology and neurodegeneration, respectively. The RGD declining group displayed a higher vascular risk and greater WMH volume than the RGD stable group, whereas no such difference was found in the aMCI subjects. In contrast, the aMCI declining group displayed a smaller left hippocampal volume than the aMCI stable group, whereas no such difference was found in the RGD subjects. Furthermore, greater increases in the WHM volume correlated with greater decreases in global cognitive function in the RGD declining group, and greater decreases in the left hippocampal volume correlated with greater decreases in global cognitive function in the aMCI declining group. In conclusion, the cognitive decline in RGD patients is associated with vascular burden, whereas the cognitive decline in aMCI patients is associated with neurodegeneration. These findings could contribute to a better understanding of the specific mechanisms of the development of dementia in each condition.

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Periventricular white matter hyperintensities and the risk of dementia: a CREDOS study

Abstract: WMH differentially predict dementia by region and severity. Our findings suggest that PWMH may play an independent role in the pathogenesis of dementia, especially in AD.

Cited by 63 publications

References 35 publications

The Temporal Relationships between White Matter Hyperintensities, Neurodegeneration, Amyloid β, and Cognition

The Temporal Relationships between White Matter Hyperintensities, Neurodegeneration, Amyloid β, and Cognition

Application of the DSM-5 Criteria for Major Neurocognitive Disorder to Vascular MCI Patients

Divergent Roles of Vascular Burden and Neurodegeneration in the Cognitive Decline of Geriatric Depression Patients and Mild Cognitive Impairment Patients

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