Small Vessel Disease and Associations with Cerebrospinal Fluid Amyloid, Tau, and Neurodegeneration (ATN) Biomarkers and Cognition in Young Onset Dementia

2020 ◽  
Vol 77 (3) ◽  
pp. 1305-1314
Author(s):  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Anne Cristine Guevarra ◽  
Benjamin Wong ◽  
TingTing Yong ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Grey Matter ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Memory Clinic ◽  
Young Onset ◽  
Vessel Disease ◽  
Young Onset Dementia ◽  
Global Cognition

Background: Small vessel disease (SVD) and Alzheimer’s disease (AD) frequently coexist; however, it remains unclear how they collectively affect cognition. Objective: We investigated associations between SVD and AD biomarkers, namely amyloid, tau, and neurodegeneration (ATN) in young onset dementia (YOD) and explored how SVD and ATN interact to affect cognition. Methods: 80 YOD individuals were recruited from a memory clinic. SVD burden (SVD+) was operationalized as a score >1 on the Staals scale and ATN was measured using cerebrospinal fluid (CSF). Results: SVD+ was associated with lower CSF Aβ1–42 (B = –0.20, 95% CI: –0.32 to –0.08) and greater neurodegeneration, indexed as hippocampal atrophy (B = –0.24, 95% CI: –0.40 to –0.04). SVD+ was not associated with tau. Cognitive impairment was associated with CSF Aβ1–42 (B = –0.35, 95% CI: –0.55 to –0.18) but not SVD. Rather, SVD was indirectly associated with cognition via reduced CSF Aβ1–42, specifically with global cognition (B = –0.03, 95% CI: –0.09 to –0.01) and memory (B = 0.08, 95% CI: –.01 to .21). SVD was indirectly associated with cognition via increased neurodegeneration in grey matter (Global cognition: B = –0.06, 95% CI: –0.17 to –0.03; Memory: B = 0.05, 95% CI: 0.01 to 0.18) and the hippocampus (Global cognition: B = –0.05, 95% CI: –0.11 to –0.01; Memory: B = 0.06, 95% CI: 0.01 to 0.17). Conclusion: In YOD, SVD burden was associated with AD pathology, namely CSF Aβ1–42. SVD indirectly contributed to cognitive impairment via reducing CSF Aβ1–42 and increasing neurodegeneration.

Brain amyloid β, cerebral small vessel disease, and cognition

Neurology ◽  
2020 ◽  
Vol 95 (21) ◽  
pp. e2845-e2853 ◽  
Author(s):  
Francis N. Saridin ◽  
Saima Hilal ◽  
Steven G. Villaraza ◽  
Anthonin Reilhac ◽  
Bibek Gyanwali ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Neuropsychological Testing ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Memory Clinic ◽  
Alzheimer Dementia ◽  
Vessel Disease

ObjectiveTo evaluate the association between brain amyloid β (Aβ) and cerebral small vessel disease (CSVD) markers, as well as their joint effect on cognition, in a memory clinic study.MethodsA total of 186 individuals visiting a memory clinic, diagnosed with no cognitive impairment, cognitive impairment no dementia (CIND), Alzheimer dementia (AD), or vascular dementia were included. Brain Aβ was measured by [11C] Pittsburgh compound B–PET global standardized uptake value ratio (SUVR). CSVD markers including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs) were graded on MRI. Cognition was assessed by neuropsychological testing.ResultsAn increase in global SUVR is associated with a decrease in Mini-Mental State Examination (MMSE) in CIND and AD, as well as a decrease in global cognition Z score in AD, independent of age, education, hippocampal volume, and markers of CSVD. A significant interaction between global SUVR and WMH was found in relation to MMSE in CIND (P for interaction: 0.009), with an increase of the effect size of Aβ (β = −6.57 [−9.62 to −3.54], p < 0.001) compared to the model without the interaction term (β = −2.91 [−4.54 to −1.29], p = 0.001).ConclusionHigher global SUVR was associated with worse cognition in CIND and AD, but was augmented by an interaction between global SUVR and WMH only in CIND. This suggests that Aβ and CSVD are independent processes with a possible synergistic effect between Aβ and WMH in individuals with CIND. There was no interaction effect between Aβ and lacunes or CMBs. Therefore, in preclinical phases of AD, WMH should be targeted as a potentially modifiable factor to prevent worsening of cognitive dysfunction.

scholarly journals Higher Total Cerebral Small Vessel Disease Burden Was Associated With Mild Cognitive Impairment and Overall Cognitive Dysfunction: A Propensity Score-Matched Case–Control Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Xuanting Li ◽  
Junliang Yuan ◽  
Wei Qin ◽  
Lei Yang ◽  
Shuna Yang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Case Control Study ◽  
Small Vessel Disease ◽  
Case Control ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Global Cognition ◽  
Control Study

Background and ObjectiveThe combination of neuroimaging and cognition characteristics may provide complementary information for early identification of mild cognitive impairment (MCI). This study aimed to establish the clinical relevance between cerebral small vessel disease (CSVD) burden and MCI and further explored the cognitive characteristics linked to CSVD applying a propensity score matching (PSM) approach.MethodsThe study was designed as a case–control study. All the subjects underwent the standard clinical assessments, neuropsychological testing battery (including global cognition, memory, executive function, and speed and motor control domains), and brain magnetic resonance imaging (MRI). A 1:2 nearest-neighbor matching approach without replacement was employed with a caliper of 0.15 in the PSM approach.ResultsA total of 84 MCI patients and 186 cognitively normal controls were included in this study. After PSM, 74 MCI patients and 129 controls were successfully matched, and the covariate imbalance was well eliminated. Compared with controls, the MCI group had more severe CSVD burden. In the binary logistic regression analysis, CSVD was associated with MCI after adjusting for all confounders. The results of multivariate linear regression analyses showed that higher total MRI CSVD burden was related to the deficit of cognitive performance in global cognition and three important cognitive domains after adjusting for all confounders.ConclusionCerebral small vessel disease was an independent risk factor of MCI. Moreover, higher total MRI CSVD burden was associated with the overall cognitive impairment among middle-aged and elderly Chinese adults.

scholarly journals Cerebrovascular Disease and Associations with ATN Biomarkers and Cognition in Young Onset Dementia

2019 ◽  
Author(s):  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Anne Cristine Guevarra ◽  
Benjamin Wong ◽  
TingTing Yong ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Grey Matter ◽  
Hippocampal Volume ◽  
Brain Volumes ◽  
Young Onset ◽  
Neuropsychological Assessments ◽  
Young Onset Dementia ◽  
Global Cognition ◽  
T Tau

Abstract Background: Cerebrovascular disease (CVD) and Alzheimer’s disease (AD) frequently coexist however the mechanism by which they collectively affect cognition remains unclear, particularly in young onset dementia (YOD). We investigated associations between CVD and AD biomarkers, namely amyloid, tau and neurodegeneration (ATN) in YOD, and explored how CVD and ATN interact to affect cognition.Methods: 80 YOD individuals with mild dementia, mean age 57.73 (SD = 6.01) years were recruited from a memory clinic. MRI visual ratings were used to operationalize CVD burden (CVD+) as a score >1 on the Staals CVD scale. ATN biomarkers were measured using cerebrospinal fluid (CSF) and cognition was measured using neuropsychological assessments.Results: CVD+ individuals had lower CSF Aβ1-42 compared to CVD- (t[78] = -1.97, p = .05), while demographics, cognition, cardiovascular risk factors, brain volumes and tau were consistent across the groups. CVD+ was associated with lower CSF Aβ1-42 (B = -.20, 95%CI: -.32 to -.08) and greater neurodegeneration, indexed as lower grey matter (B = -.15, 95%CI: -.28 to .02) and hippocampal volume (B = -.24, 95%CI: -.40 to -.04). CVD+ was not associated with p-tau or t-tau. Cognitive impairment was associated with CSF Aβ1-42 (B = -.35, 95%CI: -.55 to -.18) but not CVD. Rather, CVD was indirectly associated with cognition via reduced CSF Aβ1-42, specifically with global cognition (B = -.03, 95%CI: -.09 to -.01) and memory (B = .08, 95%CI: -.09 to -.01). CVD was further indirectly associated with cognition via increased neurodegeneration in total grey matter (Global cognition: B = -.06, 95%CI: -.09 to -.03; Memory: B = .05, 95%CI: .01 to .18) and the hippocampus (Global cognition: B = -.05, 95%CI: -.11 to -.01; Memory: B = .06, 95%CI: .01 to .17). CVD was not found to moderate the strength or direction of the relationship between ATN and cognition. Conclusion: In YOD, CVD burden is linked to upstream AD mechanisms, such as CSF Aβ1-42, as well as downstream neurodegeneration. CVD indirectly contributes to cognitive impairment via these AD mechanisms. Clinical implications support the aggressive management of CVD to delay AD in young adults.

Abstract P626: Periodontal Disease is Independently Associated With Cerebral Small Vessel Disease

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Forrest Lowe ◽  
Souvik Sen ◽  
Hamdi S Adam ◽  
Ryan Demmer ◽  
Bruce A Wasserman ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Periodontal Disease ◽  
Small Vessel Disease ◽  
Multinomial Logistic Regression ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Periodontal Health ◽  
Vessel Disease ◽  
The Relationship

Background: Prior studies have shown the association between periodontal disease, lacunar strokes and cognitive impairment. Using the Atherosclerosis Risk in Communities (ARIC) cohort study we investigated the relationship between periodontal disease (PD) and the development of MRI verified small vessel disease. Methods: Using the ARIC database data we extracted data for 1143 (mean age 77 years, 76% white, 24% African-American and 45% male) participants assessed for PD (N=800) versus periodontal health (N=343). These participants were assessed for small vessel disease on 3T MRI as measured by the log of white matter hyperintensity volume (WMHV). WMHV were derived from a semiautomated segmentation of FLAIR images. Student t-test was then used to evaluate the relationship between small vessel disease as the log of WMHV in subjects with PD or periodontal health. Based on WMHV the patients were grouped into quartiles and the association of PD with WMHV were tested using the group in periodontal health and lowest quartile of WMHV as the reference groups. Multinomial logistic regression was used to compute crude and adjusted odds ratio (OR) for the higher quartiles of WMHV compared to the reference quartile. Results: There was a significant increase in the presence of small vessel disease measured as log WMHV in the PD cohort as compared to periodontal health cohort with p= 0.023 on Independent Sample t-est. Based on WMHV the subjects were grouped into quartiles 0-6.41, >6.41-11.56, >11.56-21.36 and >21.36 cu mm3). PD was associated with only the highest quartile of WMHV on univariate (crude OR 1.77, 95% CI 1.23-2.56) and multivariable (adjusted OR 1.61, 95% CI 1.06-2.44) analyses. The later was adjusted for age, race, gender, hypertension, diabetes and smoking. Conclusion: Based on this prospective cohort there is data to suggest that PD may be associated with cerebral small vessel disease. Maintaining proper dental health may decrease future risk for the associated lacunar strokes and vascular cognitive impairment.

Different cognitive profiles between mild cognitive impairment due to cerebral small vessel disease and mild cognitive impairment of Alzheimer’s disease origin

2009 ◽  
Vol 15 (6) ◽  
pp. 898-905 ◽  
Author(s):  
AIHONG ZHOU ◽  
JIANPING JIA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Processing Speed ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cognitive Domains ◽  
Vessel Disease

AbstractControversy surrounds the differences of the cognitive profile between mild cognitive impairment resulting from cerebral small vessel disease (MCI-SVD) and mild cognitive impairment associated with prodromal Alzheimer’s disease (MCI-AD). The aim of this study was to explore and compare the cognitive features of MCI-SVD and MCI-AD. MCI-SVD patients (n = 56), MCI-AD patients (n = 30), and normal control subjects (n = 80) were comprehensively evaluated with neuropsychological tests covering five cognitive domains. The performance was compared between groups. Tests that discriminated between MCI-SVD and MCI-AD were identified. Multiple cognitive domains were impaired in MCI-SVD group, while memory and executive function were mainly impaired in MCI-AD group. Compared with MCI-SVD, MCI-AD patients performed relatively worse on memory tasks, but better on processing speed measures. The AVLT Long Delay Free Recall, Digit Symbol Test, and Stroop Test Part A (performance time) in combination categorized 91.1% of MCI-SVD patients and 86.7% of MCI-AD patients correctly. Current study suggested a nonspecific neuropsychological profile for MCI-SVD and a more specific cognitive pattern in MCI-AD. MCI-AD patients demonstrated greater memory impairment with relatively preserved mental processing speed compared with MCI-SVD patients. Tests tapping these two domains might be potentially useful for differentiating MCI-SVD and MCI-AD patients. (JINS, 2009, 15, 898–905.)

scholarly journals A Proposed Hypothesis on Dementia: Inflammation, Small Vessel Disease, and Hypoperfusion Is the Sequence That Links All Harmful Lifestyles to Cognitive Impairment

2021 ◽  
Vol 13 ◽  
Author(s):  
Antoine M. Hakim
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cognitive Impairment ◽  
Cerebral Perfusion ◽  
Small Vessel Disease ◽  
Negative Impact ◽  
Small Vessel ◽  
Vessel Disease ◽  
Sequence Of Events ◽  
Do So

There is growing consensus that certain lifestyles can contribute to cognitive impairment and dementia, but the physiological steps that link a harmful lifestyle to its negative impact are not always evident. It is also unclear whether all lifestyles that contribute to dementia do so through the same intermediary steps. This article will focus on three lifestyles known to be risk factors for dementia, namely obesity, sedentary behavior, and insufficient sleep, and offer a unifying hypothesis proposing that lifestyles that negatively impact cognition do so through the same sequence of events: inflammation, small vessel disease, decline in cerebral perfusion, and brain atrophy. The hypothesis will then be tested in a recently identified risk factor for dementia, namely hearing deficit. If further studies confirm this sequence of events leading to dementia, a significant change in our approach to this debilitating and costly condition may be necessary, possible, and beneficial.

scholarly journals Associations between blood and cerebrospinal fluid flow impairments assessed with phase-contrast MRI and brain damage in patients with age-related cerebral small vessel disease

2019 ◽  
pp. 16-23
Author(s):  
E.I. Kremneva ◽  
B.M. Akhmetzyanov ◽  
L.A. Dobrynina ◽  
M.V. Krotenkova
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Damage ◽  
Phase Contrast ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Csf Flow ◽  
Phase Contrast Mri ◽  
Vessel Disease ◽  
Age Related

Hemodynamic parameters of blood and cerebrospinal fluid (CSF) flow can be measured in vivo using phase-contrast MRI (PC-MRI). This opens new horizons for studying the mechanisms implicated in the development and progression of age-related cerebral small vessel disease (SVD). In this paper, we analyze associations between cerebral arterial, venous and CSF flow impairments and SVD features visible on MRI. The study was carried out in 96 patients with SVD (aged 60.91 ± 6.57 years) and 23 healthy volunteers (59.13 ± 6.56 years). The protocol of the MRI examination included routine MRI sequences (T2, FLAIR, T1, SWI, and DWI) applied to assess the severity of brain damage according to STRIVE advisory standards and PC-MRI used to quantify blood flow in the major arteries and veins of the neck, the straight and upper sagittal sinuses, and CSF flow at the aqueduct level. We analyzed the associations between linear and volumetric parameters of blood/CSF flow and the degree of brain matter damage using the Fazekas scale. We observed a reduction in tABF, stVBF, sssVBF, aqLF, Saq, and ICC values and a rise in Pi associated with WMH progression, as well as a gradual decline in tABF and an increase in Pi, Saq and ICC associated with a growing number of lacunes (р < 0.05). Patients with early (< 5) MB had lower sssVBF and stVBF rates in comparison with patients without MB; aqLF, Saq, and ICC values were elevated in patients with 5 to 10 MB, as compared to patients without MB or early (< 5) MB. The established associations between MRI findings in patients with SVD and blood/CSF flow impairments suggest the important role of mechanisms implicated in the disruption of Monro–Kellie intracranial homeostasis in promoting SVD.

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