White matter hyperintensities and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 36 prospective studies

Hu, He‐Ying; Ou, Ya‐Nan; Shen, Xue‐Ning; Qu, Yi; Ma, Ya‐Hui; Wang, Zuo-Teng; Dong, Qiang; Tan, Lan; Yu, Jin‐Tai

doi:10.1016/j.neubiorev.2020.11.007

Cited by 170 publications

(135 citation statements)

References 85 publications

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“…This study highlights WMH as an independent predictor for decline in cognition [33]. This is also in keeping with the most recent meta-analysis, which revealed that there is an association between development of dementia and the severity or increased grade of WMH [34]. We therefore recommend that Fazekas rating be used consistently in cranial MRI reports.…”

Section: Discussionsupporting

confidence: 88%

Demographic and Clinical Profile of Patients with Mild Cognitive Impairment Seen at St. Luke’s Medical Center-Global City Memory Service

Mojica

Ampil

et al. 2021

Dement Geriatr Cogn Disord

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Introduction: Mild cognitive impairment (MCI) is a dynamic state, which has evolved into a highly defined condition due to its association with dementia syndromes. There are no published data on the demographic and clinical characteristics of MCI in the Philippines. These data will help in defining the population at risk for the condition and in modifying the factors for its prevention. Methods: From 2010 to 2019, 434 subjects were diagnosed with MCI based on the criteria published by the International Working Group on MCI last 2004. The demographic profile, vascular risk factors, and levels of Vitamin B12, Vitamin D, and homocysteine were reviewed. Results of neuropsychological tests, such as Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Mini-Mental State Exam (MMSE), and Montreal Cognitive Assessment (MoCA), were collected. The Fazekas score of the cranial magnetic resonance imaging of patients was also considered. Results: The median age was 72 years [34–97] with 58.3% females. The median years of education were 14 [4–28]. Median ADAS-Cog, MMSE, and MoCA scores were 11.3 [0–27.67], 27 [13–30], and 21 [7–30], respectively. Hypertension and dyslipidemia were present in 66.8% and 64.1%, respectively. Normal homocysteine, Vitamin B12, and Vitamin D levels were found in 64.2%, 59.8%, and 48.8%, respectively. The median Fazekas score was 1 (59.4%). Conclusion: This is the first study to document the demographic and clinical profile of Filipinos with MCI in a clinical setting. This review serves as a foundation for increased understanding of MCI with the ultimate goal of controlling the factors which may impact its prevention.

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Section: Discussionsupporting

confidence: 88%

Demographic and Clinical Profile of Patients with Mild Cognitive Impairment Seen at St. Luke’s Medical Center-Global City Memory Service

Mojica

Ampil

et al. 2021

Dement Geriatr Cogn Disord

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“…The progression of WMH is associated with further decreases in global cognitive scores ( 24 , 25 ). Besides, above certain severity, WMH increased the risk of all-cause dementia ( 26 ). Our regression analysis were consistent with the findings from previous studies.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of White Matter Hyperintensities in Cognitively Impaired Patients With Cerebral Small Vessel Disease

Wang

Jin

et al. 2021

Front. Immunol.

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ObjectiveSimilar white matter hyperintensities (WMH) might have different impact on the cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study is to assess the possible factors related to the heterogeneity of WMH in cognitively impaired patients with CVSD.MethodsWe analyzed data from a cohort of patients with CVSD who were recruited consecutively from the Beijing Tiantan Hospital from 2015 to 2020. WMH, lacunes, enlarged perivascular space (ePVS), microbleeds and lacunar infarcts were rated on brain MRI. A score of <26 on the Montreal Cognitive Assessment (MoCA) indicated cognitive impairment. A mismatch was defined as the severity of WMH not matching the severity of cognitive dysfunction. Type-1 mismatch was defined as a mild WMH (Fazekas score = 0-1) associated with cognitive impairment, and type-2 mismatch was defined as a severe WMH (Fazekas score = 5-6) associated with normal cognitive function. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced SWI on 3-Tesla MRI was used to image the penetrating arteries in basal ganglia to explore the underlying mechanism of this mismatch. Multivariable logistic regression was used to analyze the association between the imaging features and cognitive impairment.ResultsIn 156 patients, 118 (75.6%) had cognitive impairment and 37 (23.7%) showed mismatch. Twenty five (16.0%) had type-1 mismatch and 12 (7.7%) had type-2 mismatch. Regression analysis found that WMH, lacunes, microbleeds and total CSVD scores were associated with cognitive impairment and were independent of vascular risk factors. However, lacunes, microbleeds and total CSVD scores were related to the mismatch between WMH and cognitive impairment (p=0.006, 0.005 and 0.0001, respectively). Specially, age and ePVS in basal ganglia were related to type-1 mismatch (p=0.04 and 0.02, respectively); microbleeds and total CSVD scores were related to type-2 mismatch (p=0.01 and 0.03, respectively). Although the severity of WMH was similar, the injury scores of penetrating arteries were significantly different between those with and without cognitive impairment (p=0.04).ConclusionsHeterogeneity of WMH was present in cognitively impaired patients with CSVD. Conventional imaging features and injury of penetrating arteries may account for such heterogeneity, which can be a hallmark for early identification and prevention of cognitive impairment.

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“…OH may be directly linked to falls due to reduced cerebral perfusion and a subsequent reduction in oxygenation in the brain within seconds of standing up from a lying or seated position [ 23 ]. OH has also been associated with cerebral white matter hyperintensities [ 24 ], which have been associated with deficits in gait [ 25 ], cognitive function [ 26 ] and mood [ 27 ], all of which may indirectly link OH and falls. The prevalence of hypertension increases with age and is also associated with white matter lesions [ 28 ], therefore it is not surprising that there is a strong association between OH and hypertension [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Is orthostatic hypotension and co-existing supine and seated hypertension associated with future falls in community-dwelling older adults? Results from The Irish Longitudinal Study on Ageing (TILDA)

2021

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Orthostatic hypotension (OH) often co-exists with hypertension. As increasing age affects baroreflex sensitivity, it loses its ability to reduce blood pressure when lying down. Therefore, supine hypertension may be an important indicator of baroreflex function. This study examines (i) the association between OH and future falls in community-dwelling older adults and (ii) if these associations persist in those with co-existing OH and baseline hypertension, measured supine and seated. Data from 1500 community-dwelling adults aged ≥65 years from The Irish Longitudinal Study on Ageing (TILDA) were used. Continuous beat-to-beat blood pressure was measured using digital photoplethysmography during an active stand procedure with OH defined as a drop in systolic blood pressure (SBP) ≥20 mmHg and/or ≥10 mm Hg in diastolic blood pressure (DBP) within 3 minutes of standing. OH at 40 seconds (OH40) was used as a marker of impaired early stabilisation and OH sustained over the second minute (sustained OH) was used to indicate a more persistent deficit, similar to traditional OH definitions. Seated and supine hypertension were defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Modified Poisson models were used to estimate relative risk of falls (recurrent, injurious, unexplained) and syncope occurring over four year follow-up. OH40 was independently associated with recurrent (RR = 1.30, 95% CI = 1.02,1.65), injurious (RR = 1.43, 95% CI = 1.13,1.79) and unexplained falls (RR = 1.55, 95% CI = 1.13,2.13). Sustained OH was associated with injurious (RR = 1.55, 95% CI = 1.18,2.05) and unexplained falls (RR = 1.63, 95% CI = 1.06,2.50). OH and co-existing hypertension was associated with all falls outcomes but effect sizes were consistently larger with seated versus supine hypertension. OH, particularly when co-existing with hypertension, was independently associated with increased risk of future falls. Stronger effect sizes were observed with seated versus supine hypertension. This supports previous findings and highlights the importance of assessing orthostatic blood pressure behaviour in older adults at risk of falls and with hypertension. Observed associations may reflect underlying comorbidities, reduced cerebral perfusion or presence of white matter hyperintensities.

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White matter hyperintensities and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 36 prospective studies

Cited by 170 publications

References 85 publications

Demographic and Clinical Profile of Patients with Mild Cognitive Impairment Seen at St. Luke’s Medical Center-Global City Memory Service

Demographic and Clinical Profile of Patients with Mild Cognitive Impairment Seen at St. Luke’s Medical Center-Global City Memory Service

Heterogeneity of White Matter Hyperintensities in Cognitively Impaired Patients With Cerebral Small Vessel Disease

Is orthostatic hypotension and co-existing supine and seated hypertension associated with future falls in community-dwelling older adults? Results from The Irish Longitudinal Study on Ageing (TILDA)

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