Cerebral amyloid angiopathy (CAA) is frequently found post mortem in Alzheimer’s dementia, but often undetected during life especially since in vivo hallmarks of CAA and its vascular damage become... Show moreCerebral amyloid angiopathy (CAA) is frequently found post mortem in Alzheimer’s dementia, but often undetected during life especially since in vivo hallmarks of CAA and its vascular damage become overt relatively late in the disease process. Decreased neurovascular coupling to visual stimulation has been put forward as an early MRI marker for CAA disease severity. The current study investigates the role of neurovascular coupling in AD related dementia and its early stages. We included 25 subjective cognitive impairment, 33 mild cognitive impairment and 17 dementia patients and 44 controls. All participants underwent magnetic resonance imaging of the brain and neuropsychological assessment. Univariate general linear modeling analyses were used to assess neurovascular coupling between patient groups and controls. Moreover, linear regression analyses was used to assess the associations between neurovascular coupling and cognition. Our data show that BOLD amplitude is lower in dementia (mean 0.8 ± 0.2, p = 0.001) and MCI patients (mean 0.9 ± 0.3, p = 0.004) compared with controls (mean 1.1 ± 0.2). A low BOLD amplitude was associated with low scores in multiple cognitive domains. We conclude that cerebrovascular dysfunction, most likely due CAA, is an important comorbidity in early stages of dementia and has an independent effect on cognition. Show less
BackgroundThe diagnosis of probable cerebral amyloid angiopathy (CAA) is currently mostly based on characteristics of brain MRI. Blood biomarkers would be a cost-effective, easily accessible... Show moreBackgroundThe diagnosis of probable cerebral amyloid angiopathy (CAA) is currently mostly based on characteristics of brain MRI. Blood biomarkers would be a cost-effective, easily accessible diagnostic method that may complement diagnosis by MRI and aid in monitoring disease progression. We studied the diagnostic potential of plasma Aβ38, Aβ40, and Aβ42 in patients with hereditary Dutch-type CAA (D-CAA) and sporadic CAA (sCAA).MethodsAll Aβ peptides were quantified in the plasma by immunoassays in a discovery cohort (11 patients with presymptomatic D-CAA and 24 patients with symptomatic D-CAA, and 16 and 24 matched controls, respectively) and an independent validation cohort (54 patients with D-CAA, 26 presymptomatic and 28 symptomatic, and 39 and 46 matched controls, respectively). In addition, peptides were quantified in the plasma in a group of 61 patients with sCAA and 42 matched controls. We compared Aβ peptide levels between patients and controls using linear regression adjusting for age and sex.ResultsIn the discovery cohort, we found significantly decreased levels of all Aβ peptides in patients with presymptomatic D-CAA (Aβ38: p < 0.001; Aβ40: p = 0.009; Aβ42: p < 0.001) and patients with symptomatic D-CAA (Aβ38: p < 0.001; Aβ40: p = 0.01; Aβ42: p < 0.001) compared with controls. In contrast, in the validation cohort, plasma Aβ38, Aβ40, and Aβ42 were similar in patients with presymptomatic D-CAA and controls (Aβ38: p = 0.18; Aβ40: p = 0.28; Aβ42: p = 0.63). In patients with symptomatic D-CAA and controls, plasma Aβ38 and Aβ40 were similar (Aβ38: p = 0.14; Aβ40: p = 0.38), whereas plasma Aβ42 was significantly decreased in patients with symptomatic D-CAA (p = 0.033). Plasma Aβ38, Aβ40, and Aβ42 levels were similar in patients with sCAA and controls (Aβ38: p = 0.092; Aβ40: p = 0.64. Aβ42: p = 0.68).ConclusionsPlasma Aβ42 levels, but not plasma Aβ38 and Aβ40, may be used as a biomarker for patients with symptomatic D-CAA. In contrast, plasma Aβ38, Aβ40, and Aβ42 levels do not appear to be applicable as a biomarker in patients with sCAA. Show less
Drenth, N.; Foster-Dingley, J.C.; Bertens, A.S.; Ottenheim, N.R.; Mast, R.C. van der; Rombouts, S.A.R.B.; ... ; Grond, J. van der 2023
Ageing is associated with functional reorganization that is mainly characterized by declining functional connectivity due to general neurodegeneration and increasing incidence of disease.... Show moreAgeing is associated with functional reorganization that is mainly characterized by declining functional connectivity due to general neurodegeneration and increasing incidence of disease. Functional connectivity has been studied across the lifespan; however, there is a paucity of research within the older groups (>= 75 years) where neurodegeneration and disease prevalence are at its highest. In this cross-sectional study, we investigated associations between age and functional connectivity and the influence of cerebral small vessel disease (CSVD)-a common age-related morbidity-in 167 community-dwelling older adults aged 75-91 years (mean = 80.3 +/- 3.8). Resting-state functional MRI was used to determine functional connectivity within ten standard networks and calculate the whole brain graph theoretical measures global efficiency and clustering coefficient. CSVD features included white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and atrophy that were assessed in each individual and a composite score was calculated. Both main and interaction effects (age*CSVD features) on functional connectivity were studied. We found stable levels of functional connectivity across the age range. CSVD was not associated with functional connectivity measures. To conclude, our data show that the functional architecture of the brain is relatively unchanged after 75 years of age and not differentially affected by individual levels of vascular pathology. Show less
Harten, T.W. van; Rooden, S. van; Koemans, E.A.; Opstal, A.M. van; Greenberg, S.M.; Grond, J. van der; ... ; Osch, M.J.P. van 2023
Cerebral vascular reactivity quantified using blood oxygen level-dependent functional MRI in conjuncture with a visual stimulus has been proven to be a potent and early marker for cerebral amyloid... Show moreCerebral vascular reactivity quantified using blood oxygen level-dependent functional MRI in conjuncture with a visual stimulus has been proven to be a potent and early marker for cerebral amyloid angiopathy. This work investigates the influence of different postprocessing methods on the outcome of such vascular reactivity measurements. Three methods for defining the region of interest (ROI) over which the reactivity is measured are investigated: structural (transformed V1), functional (template based on the activation of a subset of subjects), and percentile (11.5 cm(3) most responding voxels). Evaluation is performed both in a test-retest experiment in healthy volunteers (N = 12), as well as in 27 Dutch-type cerebral amyloid angiopathy patients and 33 age- and sex-matched control subjects. The results show that the three methods select a different subset of voxels, although all three lead to similar outcome measures in healthy subjects. However, in (severe) pathology, the percentile method leads to higher reactivity measures than the other two, due to circular analysis or "double dipping" by defining a subject-specific ROI based on the strongest responses within each subject. Furthermore, while different voxels are included in the presence of lesions, this does not necessarily result in different outcome measures. In conclusion, to avoid bias created by the method, either a structural or a functional method is recommended. Both of these methods provide similar reactivity measures, although the functional ROI appears to be less reproducible between studies, because slightly different subsets of voxels were found to be included. On the other hand, the functional method did include fewer lesion voxels than the structural method. Show less
Dijk, S.E. van; Lak, J.; Drenth, N.; Hafkemeijer, A.; Rombouts, S.A.R.B.; Grond, J. van der; Rooden, S. van 2022
Background: Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before... Show moreBackground: Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test-retest reliability of these parameters should be assessed. Purpose: Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test-retest reliability of these parameters. Study Type: Prospective-observational. Population: Eighty-six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D-CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D-CAA mutation carriers (mean age 54 years, 70% female). Field Strength/Sequence: 3-T, three-dimensional (3D) T1-weighted MRI and gradient echo BOLD fMRI. Assessment: To assess test-retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3-week interval for each subject. Statistical Tests: Linear regression analyses and two-way mixed absolute agreement intra-class correlation approach. Results: Healthy aging was associated with decreased BOLD amplitude (beta = -0.711) and prolonged time to baseline (beta = 0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test-retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856-0.910) and presymptomatic D-CAA mutation carriers (ICC 0.959-0.981). In symptomatic D-CAA mutation carriers, test-retest reliability was poor for all parameters (ICCs < 0.5). Data Conclusion: Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D-CAA mutation carriers, but not in symptomatic D-CAA mutation carriers. Show less
Dijk, S.E. van; Lak, J.; Drenth, N.; Hafkemeijer, A.; Rombouts, S.A.R.B.; Grond, J. van der; Rooden, S. van 2022
Background: Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before... Show moreBackground: Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test-retest reliability of these parameters should be assessed. Purpose: Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test-retest reliability of these parameters. Study Type: Prospective-observational. Population: Eighty-six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D-CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D-CAA mutation carriers (mean age 54 years, 70% female). Field Strength/Sequence: 3-T, three-dimensional (3D) T1-weighted MRI and gradient echo BOLD fMRI. Assessment: To assess test-retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3-week interval for each subject. Statistical Tests: Linear regression analyses and two-way mixed absolute agreement intra-class correlation approach. Results: Healthy aging was associated with decreased BOLD amplitude (beta = -0.711) and prolonged time to baseline (beta = 0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test-retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856-0.910) and presymptomatic D-CAA mutation carriers (ICC 0.959-0.981). In symptomatic D-CAA mutation carriers, test-retest reliability was poor for all parameters (ICCs < 0.5). Data Conclusion: Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D-CAA mutation carriers, but not in symptomatic D-CAA mutation carriers. Show less
Dijk, S.E. van; Lak, J.; Drenth, N.; Hafkemeijer, A.; Rombouts, S.A.R.B.; Grond, J. van der; Rooden, S. van 2022
Background Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before... Show moreBackground Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test-retest reliability of these parameters should be assessed. Purpose Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test-retest reliability of these parameters. Study Type Prospective-observational. Population Eighty-six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D-CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D-CAA mutation carriers (mean age 54 years, 70% female). Field Strength/Sequence 3-T, three-dimensional (3D) T1-weighted MRI and gradient echo BOLD fMRI. Assessment To assess test-retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3-week interval for each subject. Statistical Tests Linear regression analyses and two-way mixed absolute agreement intra-class correlation approach. Results Healthy aging was associated with decreased BOLD amplitude (beta = -0.711) and prolonged time to baseline (beta = 0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test-retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856-0.910) and presymptomatic D-CAA mutation carriers (ICC 0.959-0.981). In symptomatic D-CAA mutation carriers, test-retest reliability was poor for all parameters (ICCs < 0.5). Data Conclusion Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D-CAA mutation carriers, but not in symptomatic D-CAA mutation carriers. Show less
Dijk, S.E. van; Grond, J. van der; Lak, J.; Berg-Huysmans, A. van den; Labadie, G.; Terwindt, G.M.; ... ; Rooden, S. van 2022
Background: Hemorrhagic and ischemic magnetic resonance imaging lesions as well as the more recently described decrease in vasomotor reactivity have been suggested as possible biomarkers for... Show moreBackground: Hemorrhagic and ischemic magnetic resonance imaging lesions as well as the more recently described decrease in vasomotor reactivity have been suggested as possible biomarkers for cerebral amyloid angiopathy (CAA). Analyses of these markers have been primarily cross-sectional during the symptomatic phase of the disease, with little data on their longitudinal progression, particularly in the presymptomatic phase of the disease when it may be most responsive to treatment. We used the unique opportunity provided by studying Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) to determine longitudinal progression of CAA biomarkers during the presymptomatic as well as the symptomatic phase of the disease. Methods: In this longitudinal case-control study, magnetic resonance imaging markers and cognitive performance were assessed at baseline and after approximate to 4 years in 10 presymptomatic and 6 symptomatic D-CAA mutation carriers and 20 control subjects. These magnetic resonance imaging markers included hemorrhagic and ischemic manifestations, measurements of cerebral blood flow, and vasomotor reactivity to visual stimulation. Results: In presymptomatic D-CAA mutations carriers, vasomotor reactivity showed a decline over time for blood-oxygen-level-dependent amplitude (P=0.011) and prolongation of time to peak (P<0.001). In contrast, no significant changes in hemorrhagic markers, ischemic markers, cerebral blood flow, and cognition were found. In symptomatic D-CAA mutation carriers, the number of intracerebral hemorrhages increased over the 4-year period (P=0.007). Conclusions: Our findings indicate that in the presymptomatic phase of D-CAA, cerebrovascular reactivity measured by the blood-oxygen-level-dependent amplitude and time to peak to visual stimulation progressively worsens and can thus be regarded as a disease progression marker. In the symptomatic phase, the most salient marker of progression appears to be recurrent intracerebral hemorrhage. Show less
Background: Deep medullary vein (DMV) changes occur in cerebral small vessel diseases (SVD) and in Alzheimer's disease. Cerebral amyloid angiopathy (CAA) is a common SVD that has a high co... Show moreBackground: Deep medullary vein (DMV) changes occur in cerebral small vessel diseases (SVD) and in Alzheimer's disease. Cerebral amyloid angiopathy (CAA) is a common SVD that has a high co-morbidity with Alzheimer's disease. So far, DMVs have not been evaluated in CAA. Objective: To evaluate DMVs in Dutch-type hereditary CAA (D-CAA) mutation carriers and controls, in relation to MRI markers associated with D-CAA. Methods: Quantitative DMV parameters length, tortuosity, inhomogeneity, and density were quantified on 7 Tesla 3D susceptibility weighted MRI in pre-symptomatic D-CAA mutation carriers (n = 8), symptomatic D-CAA mutation carriers (n = 8), and controls (n = 25). HemorrhagicMRImarkers (cerebral microbleeds, intracerebral hemorrhages, cortical superficial siderosis, convexity subarachnoid hemorrhage), non-hemorrhagic MRI markers (white matter hyperintensities, enlarged perivascular spaces, lacunar infarcts, cortical microinfarcts), cortical grey matter perfusion, and diffusion tensor imaging parameters were assessed in D-CAA mutation carriers. Univariate general linear analysis was used to determine associations between DMV parameters and MRI markers. Results: QuantitativeDMVparameters length, tortuosity, inhomogeneity, and density did not differ between pre-symptomatic D-CAA mutation carriers, symptomatic D-CAA mutation carriers, and controls. No associations were found between DMV parameters and MRI markers associated with D-CAA.Conclusion: This study indicates that vascular amyloid-beta deposition does not affectDMVparameters. In patients with CAA, DMVs do not seem to play a role in the pathogenesis of MRI markers associated with CAA. Show less
Background and Purpose:Cortical calcifications have been reported in patients with cerebral amyloid angiopathy (CAA), although their prevalence and pathophysiology are unknown. We investigated the... Show moreBackground and Purpose:Cortical calcifications have been reported in patients with cerebral amyloid angiopathy (CAA), although their prevalence and pathophysiology are unknown. We investigated the frequency of calcifications on computed tomography, their association with intracerebral hemorrhage (ICH) and their coexistence with a striped pattern of the occipital cortex reflecting microcalcifications on ultra-high-field 7T-magnetic resonance imaging in Dutch-type hereditary CAA (D-CAA) and sporadic CAA.Methods:We included D-CAA mutation carriers with a proven APP (amyloid precursor protein) mutation or >= 1 lobar ICH and >= 1 first-degree relative with D-CAA and sporadic CAA patients with probable CAA according to the modified Boston criteria. D-CAA carriers were regarded symptomatic when they had a history of symptomatic ICH. We assessed the presence, location, and progression of calcifications and their association with ICH and the striped occipital cortex.Results:We found cortical calcifications in 15/81 (19% [95% CI, 11-29]) D-CAA mutation carriers (15/69 symptomatic and 0/12 presymptomatic) and in 1/59 (2% [95% CI, 0-9]) sporadic CAA patients. Calcifications were all bilateral located in the occipital lobes. In 3/15 (20%) of the symptomatic D-CAA patients the calcifications progressed over a period up to 10 years. There was evidence of an association between cortical calcifications and new ICH development (hazard ratio, 7.1 [95% CI, 0.9-54.9], log-rank P=0.03). In 7/25 D-CAA symptomatic carriers in whom a 7T-magnetic resonance imaging was performed, a striped pattern of the occipital cortex was present; in 3/3 (100%) of those with calcifications on computed tomography and 4/22 (18%) of those without calcifications.Conclusions:Occipital cortical calcifications are frequent in D-CAA but seem to be rare in sporadic CAA. Their absence in presymptomatic carriers and their association with ICH might suggest that they are a marker for advanced CAA. Cortical calcifications on computed tomography seem to be associated with the striped occipital cortex on 7T-magnetic resonance imaging which may possibly represent an early stage of calcification. Show less
Koemans, E.A.; Voigt, S.; Rasing, I.; Jolink, W.M.T.; Harten, T.W. van; Grond, J. van der; ... ; Wermer, M.J.H. 2021
Background and aimTo investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary... Show moreBackground and aimTo investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH).MethodsWe performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T-2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features.ResultsWe included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging.ConclusionWhereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA. Show less
Drenth, N.; Grond, J. van der; Rombouts, S.A.R.B.; Buchem, M.A. van; Terwindt, G.M.; Wermer, M.J.H.; ... ; Rooden, S. van 2021
Cerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage and neurological decline in the elderly. CAA results in focal brain lesions, but the influence on global brain... Show moreCerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage and neurological decline in the elderly. CAA results in focal brain lesions, but the influence on global brain functioning needs further investigation. Here we study functional brain connectivity in patients with Dutch type hereditary CAA using resting state functional MRI. Twenty-four DNA-proven Dutch CAA mutation carriers (11 presymptomatic, 13 symptomatic) and 29 age-matched control subjects were included. Using a set of standardized networks covering the entire cortex, we assessed both within- and between-network functional connectivity. We investigated group differences using general linear models corrected for age, sex and gray matter volume. First, all mutation carriers were contrasted against control subjects and subsequently presymptomatic- and symptomatic mutation carriers against control subjects separately, to assess in which stage of the disease differences could be found. All mutation carriers grouped together showed decreased connectivity in the medial and lateral visual networks, default mode network, executive control and bilateral frontoparietal networks. Symptomatic carriers showed diminished connectivity in all but one network, and between the left and right frontoparietal networks. Presymptomatic carriers also showed diminished connectivity, but only in the frontoparietal left network. In conclusion, global brain functioning is diminished in patients with CAA, predominantly in symptomatic CAA and can therefore be considered to be a late consequence of the disease. Show less
Jung, Y.J.; Viviano, R.P.; Rooden, S. van; Grond, J. van der; Rombouts, S.A.R.B.; Damoiseaux, J.S. 2021
Background: White matter hyperintensities (WMH) show a robust relationship with arterial pressure as well as objective and subjective cognitive functioning. In addition, APOE epsilon 4 carriership... Show moreBackground: White matter hyperintensities (WMH) show a robust relationship with arterial pressure as well as objective and subjective cognitive functioning. In addition, APOE epsilon 4 carriership may influence how arterial pressure affects cognitive functioning.Objective: To determine the role of region-specific WMH burden and APOE epsilon 4 carriership on the relationship between mean arterial pressure (MAP) and cognitive function as well as subjective cognitive decline (SCD).Methods: The sample consisted of 87 cognitively unimpaired middle-aged to older adults aged 50-85. We measured WMH volume for the whole brain, anterior thalamic radiation (ATR), forceps minor, and superior longitudinal fasciculus (SLF). We examined whether WMH burden mediated the relationship between MAP and cognition (i.e., TMT-A score for processing speed; Stroop performance for executive function) as well as SCD (i.e., Frequency of Forgetting (FoF)), and whether APOE epsilon 4 carriership moderated that mediation.Results: WMH burden within SLF mediated the effect of MAP on Stroop performance. Both whole brain and ATR WMH burden mediated the effect of MAP on FoF score. In the MAP-WMH-Stroop relationship, the mediation effect of SLFWMH and the effect of MAP on SLF WMH were significant only in APOE epsilon 4 carriers. In the MAP-WMH-FoF relationship, the effect of MAP on whole brain WMH burden was significant only in epsilon 4 carriers.Conclusion: WMH burden and APOE genotype explain the link between blood pressure and cognitive function and may enable a more accurate assessment of the effect of high blood pressure on cognitive decline and risk for dementia. Show less
Drenth, N.; Grond, J. van der; Rombouts, S.A.R.B.; Buchem, M.A. van; Terwindt, G.M.; Wermer, M.J.H.; ... ; Rooden, S. van 2021
Cerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage and neurological decline in the elderly. CAA results in focal brain lesions, but the influence on global brain... Show moreCerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage and neurological decline in the elderly. CAA results in focal brain lesions, but the influence on global brain functioning needs further investigation. Here we study functional brain connectivity in patients with Dutch type hereditary CAA using resting state functional MRI. Twenty-four DNA-proven Dutch CAA mutation carriers (11 presymptomatic, 13 symptomatic) and 29 age-matched control subjects were included. Using a set of standardized networks covering the entire cortex, we assessed both within- and between-network functional connectivity. We investigated group differences using general linear models corrected for age, sex and gray matter volume. First, all mutation carriers were contrasted against control subjects and subsequently presymptomatic- and symptomatic mutation carriers against control subjects separately, to assess in which stage of the disease differences could be found. All mutation carriers grouped together showed decreased connectivity in the medial and lateral visual networks, default mode network, executive control and bilateral frontoparietal networks. Symptomatic carriers showed diminished connectivity in all but one network, and between the left and right frontoparietal networks. Presymptomatic carriers also showed diminished connectivity, but only in the frontoparietal left network. In conclusion, global brain functioning is diminished in patients with CAA, predominantly in symptomatic CAA and can therefore be considered to be a late consequence of the disease. Show less
Schultz, A.P.; Kloet, R.W.; Sohrabi, H.R.; Weerd, L. van der; Rooden, S. van; Wermer, M.J.H.; ... ; Dominantly Inherited Alzheimer N 2019
Background:Research in older adults with subjective cognitive decline (SCD) has mainly focused on Alzheimer’s disease (AD)-related MRI markers, such as hippocampal volume. However, small vessel... Show moreBackground:Research in older adults with subjective cognitive decline (SCD) has mainly focused on Alzheimer’s disease (AD)-related MRI markers, such as hippocampal volume. However, small vessel disease (SVD) is currently established as serious comorbidity in dementia and its preliminary stages. It is therefore important to examine SVD markers in addition to AD markers in older adults presenting with SCD.Objective:The aim of our study was to elucidate the role of SVD markers in late middle-aged to older adults with and without SCD in addition to the commonly found role of AD markers (hippocampal volume).Methods:67 healthy late middle-aged to older adults participated in this study (mean age 68 years); 25 participants with SCD and 42 participants without SCD. We evaluated quantitative as well as qualitative AD markers (i.e., hippocampal volume and medial temporal lobe atrophy (MTA) scale) and SVD markers (i.e., white matter hyperintensities (WMH) volume, Fazekas scale, microbleeds, and lacunar infarcts), and neuropsychological function and amount of memory complaints.Results:We found a significant effect of SCD on hippocampal atrophy, as assessed using the MTA scale, but not on hippocampal volume. In addition, we found a significant effect of SCD, and amount of memory complaints, on WMH volume and Fazekas score, suggesting larger WMH volumes in participants with SCD.Conclusion:SVD MRI markers are related to amount of memory complaints, in addition to the commonly observed AD MRI markers, as demonstrated by the greater WMHs in healthy late middle-aged to older adults with SCD. Show less
Rooden, S. van; Berg-Huysmans, A.A. van den; Croll, P.H.; Labadie, G.; Hayes, J.M.; Viviano, R.; ... ; Damoiseaux, J.S. 2018
