Postmortem studies show pathological changes in the striatum in Alzheimer's disease (AD). Here, we examine the surface of the striatum in AD and assess whether changes of the surface are associated... Show morePostmortem studies show pathological changes in the striatum in Alzheimer's disease (AD). Here, we examine the surface of the striatum in AD and assess whether changes of the surface are associated with impaired cognitive functioning. The shape of the striatum (n. accumbens, caudate nucleus, and putamen) was compared between 35 AD patients and 35 individuals without cognitive impairment. The striatum was automatically segmented from 3D T1 magnetic resonance images and automatic shape modeling tools (Growing Adaptive Meshes) were applied for morphometrical analysis. Repeated permutation tests were used to identify locations of consistent shape deformities of the striatal surface in AD. Linear regression models, corrected for age, gender, educational level, head size, and total brain parenchymal volume were used to assess the relation between cognitive performance and local surface deformities. In AD patients, differences of shape were observed on the medial head of the caudate nucleus and on the ventral lateral putamen, but not on the accumbens. The head of the caudate nucleus and ventral lateral putamen are characterized by extensive connections with the orbitofrontal and medial temporal cortices. Severity of cognitive impairment was associated with the degree of deformity of the surfaces of the accumbens, rostral medial caudate nucleus, and ventral lateral putamen. These findings provide evidence for the hypothesis that in AD primarily associative and limbic cerebral networks are affected. Show less
Es, A.C.G.M. van; Grond, J. van der; Craen, A.J.M. de; Westendorp, R.G.J.; Bollen, E.L.E.M.; Blauw, G.J.; ... ; PROSPER Study Grp 2011
OBJECTIVES Cerebral microbleeds (MBs) are an important indicator of cerebral small-vessel disease, and their prevalence increases with increasing age. Little is known about the functional... Show moreOBJECTIVES Cerebral microbleeds (MBs) are an important indicator of cerebral small-vessel disease, and their prevalence increases with increasing age. Little is known about the functional consequences of MBs in the aging population. In this study we investigated whether the presence and location of MBs are associated with cognition in the PROSPER study. METHODS For 439 subjects the number and location (cortico-subcortical, deep white matter, basal ganglia, and infratentorial) of the MBs was recorded. Difference in cognitive performance between subjects with and without MBs was calculated by entering the variables sex, age, white matter hyperintensity volume, infarction, and MBs in a linear mixed model. Differences in cognition between subjects with and without one or more MBs at different anatomic locations were assessed using the same model. RESULTS We found that after correction for sex, age, white matter hyperintensity volume, and infarction, subjects with infratentorial MBs had a significantly lower score on the Immediate Picture-Word Learning test, Delayed Picture-Word Learning, and Instrumental Activities of Daily Living. CONCLUSIONS Our data demonstrate that in elderly individuals at increased vascular risk, infratentorial MBs are associated with loss in cognitive functioning. Show less
Luyendijk, J.; Steens, S.C.A.; Ouwendijk, W.J.N.; Steup-Beekman, G.M.; Bollen, E.L.E.M.; Grond, J. van der; ... ; Buchem, M.A. van 2011
Objective. The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE [NPSLE]) are highly diverse, and their etiology is incompletely understood... Show moreObjective. The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE [NPSLE]) are highly diverse, and their etiology is incompletely understood. The aim of this study was to provide an inventory of abnormalities on conventional brain magnetic resonance imaging (MRI) in NPSLE and to interpret the findings in relation to possible underlying pathogenetic mechanisms. Methods. MR images of the first episode of active NPSLE in 74 patients were retrospectively reviewed. All patients fulfilled the American College of Rheumatology (ACR) 1982 revised criteria for the classification of SLE and were classified according to the 1999 ACR case definitions for NPSLE syndromes. We excluded patients with a history of brain disease and patients in whom other mechanisms unrelated to SLE caused the neuropsychiatric symptoms. Results. The principal findings were: 1) focal hyperintensities in white matter (WM) (49% of all patients) or both WM and gray matter (GM) (5% of all patients), suggestive of vasculopathy or vasculitis; 2) more widespread, confluent hyperintensities in the WM, suggestive of chronic hypoperfusion due to the same mechanisms; 3) diffuse cortical GM lesions (12% of all patients), compatible with an immune response to neuronal components or postseizure changes; and 4) absence of MRI abnormalities, despite signs and symptoms of active disease (42% of all patients). Conclusion. Several distinct brain MRI patterns were observed in patients with active NPSLE, suggestive of different pathogenetic mechanisms. To advance our understanding of the various processes leading to NPSLE, the radiographic manifestations may be a good starting point and useful for categorization of patients in further research. Show less
Luyendijk, J.; Steens, S.C.A.; Ouwendijk, W.J.N.; Steup-Beekman, G.M.; Bollen, E.L.E.M.; Grond, J. van der; ... ; Buchem, M.A. van 2011
OBJECTIVE The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE [NPSLE]) are highly diverse, and their etiology is incompletely understood.... Show moreOBJECTIVE The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE [NPSLE]) are highly diverse, and their etiology is incompletely understood. The aim of this study was to provide an inventory of abnormalities on conventional brain magnetic resonance imaging (MRI) in NPSLE and to interpret the findings in relation to possible underlying pathogenetic mechanisms. METHODS MR images of the first episode of active NPSLE in 74 patients were retrospectively reviewed. All patients fulfilled the American College of Rheumatology (ACR) 1982 revised criteria for the classification of SLE and were classified according to the 1999 ACR case definitions for NPSLE syndromes. We excluded patients with a history of brain disease and patients in whom other mechanisms unrelated to SLE caused the neuropsychiatric symptoms. RESULTS The principal findings were: 1) focal hyperintensities in white matter (WM) (49% of all patients) or both WM and gray matter (GM) (5% of all patients), suggestive of vasculopathy or vasculitis; 2) more widespread, confluent hyperintensities in the WM, suggestive of chronic hypoperfusion due to the same mechanisms; 3) diffuse cortical GM lesions (12% of all patients), compatible with an immune response to neuronal components or postseizure changes; and 4) absence of MRI abnormalities, despite signs and symptoms of active disease (42% of all patients). CONCLUSION Several distinct brain MRI patterns were observed in patients with active NPSLE, suggestive of different pathogenetic mechanisms. To advance our understanding of the various processes leading to NPSLE, the radiographic manifestations may be a good starting point and useful for categorization of patients in further research. Show less
Luyendijk, J.; Steens, S.C.A.; Ouwendijk, W.J.N.; Steup-Beekman, G.M.; Bollen, E.L.E.M.; Grond, J. van der; ... ; Buchem, M.A. van 2010
OBJECTIVE:: The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE or NPSLE) are highly diverse and their etiology is incompletely... Show moreOBJECTIVE:: The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE or NPSLE) are highly diverse and their etiology is incompletely understood. The aim of this study was to provide an inventory of abnormalities on conventional brain MRI in NPSLE and to interpret the findings in relation to possible underlying pathogenetic mechanisms. METHODS:: MRI exams of the first episode of active NPSLE of 74 patients were retrospectively reviewed. All patients fulfilled the revised 1982 ACR criteria for SLE and were classified according to the 1999 ACR case definitions for NPSLE syndromes. Patients with a history of brain disease, and patients in whom other mechanisms unrelated to SLE caused the neuropsychiatric symptoms, were excluded. RESULTS:: The principal findings were: 1) focal hyperintensities in WM (49% of all patients) or both WM and GM (5%) suggestive of vasculopathy or vasculitis, 2) more widespread, confluent hyperintensities in the WM, suggestive of chronic hypoperfusion due to the same mechanisms, 3) diffuse cortical GM lesions (12%), compatible with an immune response to neuronal components or post-seizure changes, and 4) absence of MRI abnormalities, despite active signs and symptoms (42%). CONCLUSION:: Several distinct brain MRI patterns were observed in patients with active NPSLE, suggestive of different pathogenetic mechanisms. To advance our understanding of the various processes leading to NPSLE, the radiological manifestations may be a good starting point and useful for categorization of patients in further research. Show less
Elderen, S.G.C. van; Roos, A. de; Craen, A.J.M. de; Westendorp, R.G.J.; Blauw, G.J.; Jukema, J.W.; ... ; Grond, J. van der 2010
OBJECTIVE To investigate progression of MRI-assessed manifestations of cerebral degeneration related to cognitive changes in a population of elderly patients with diabetes mellitus (DM) compared to... Show moreOBJECTIVE To investigate progression of MRI-assessed manifestations of cerebral degeneration related to cognitive changes in a population of elderly patients with diabetes mellitus (DM) compared to age-matched control subjects. METHODS From a randomized controlled trial (PROSPER study), a study sample of 89 patients with DM and 438 control subjects without DM aged 70-82 years were included for brain MRI scanning and cognitive function testing at baseline and reexamination after 3 years. Changes in brain atrophy, white matter hyperintensities (WMHs), number of infarctions, and cognitive function test results were determined in patients with DM and subjects without DM. Linear regression analysis was performed with correction for age, gender, hypertension, pravastatin treatment, educational level, and baseline test results. In patients with DM, baseline MRI parameters were correlated with change in cognitive function test result using linear regression analysis with covariates age and gender. RESULTS Patients with DM showed increased progression of brain atrophy (p < 0.01) after follow-up compared to control subjects. No difference in progression of WMH volume or infarctions was found. Patients with DM showed increased decline in cognitive performance on Stroop Test (p = 0.04) and Picture Learning Test (p = 0.03). Furthermore, in patients with DM, change in Picture Learning Test was associated with baseline brain atrophy (p < 0.02). CONCLUSION Our data show that elderly patients with DM without dementia have accelerated progression of brain atrophy with significant consequences in cognition compared to subjects without DM. Our findings add further evidence to the hypothesis that diabetes exerts deleterious effects on neuronal integrity. Show less
Elderen, S.G.C. van; Roos, A. de; Craen, A.J.M. de; Westendorp, R.G.J.; Blauw, G.J.; Jukema, J.W.; ... ; Grond, J. van der 2010
Objective: To investigate progression of MRI-assessed manifestations of cerebral degeneration related to cognitive changes in a population of elderly patients with diabetes mellitus (DM) compared... Show moreObjective: To investigate progression of MRI-assessed manifestations of cerebral degeneration related to cognitive changes in a population of elderly patients with diabetes mellitus (DM) compared to age-matched control subjects. Methods: From a randomized controlled trial (PROSPER study), a study sample of 89 patients with DM and 438 control subjects without DM aged 70-82 years were included for brain MRI scanning and cognitive function testing at baseline and reexamination after 3 years. Changes in brain atrophy, white matter hyperintensities (WMHs), number of infarctions, and cognitive function test results were determined in patients with DM and subjects without DM. Linear regression analysis was performed with correction for age, gender, hypertension, pravastatin treatment, educational level, and baseline test results. In patients with DM, baseline MRI parameters were correlated with change in cognitive function test result using linear regression analysis with covariates age and gender. Results: Patients with DM showed increased progression of brain atrophy (p < 0.01) after follow-up compared to control subjects. No difference in progression of WMH volume or infarctions was found. Patients with DM showed increased decline in cognitive performance on Stroop Test (p = 0.04) and Picture Learning Test (p = 0.03). Furthermore, in patients with DM, change in Picture Learning Test was associated with baseline brain atrophy (p < 0.02). Conclusion: Our data show that elderly patients with DM without dementia have accelerated progression of brain atrophy with significant consequences in cognition compared to subjects without DM. Our findings add further evidence to the hypothesis that diabetes exerts deleterious effects on neuronal integrity. Neurology (R) 2010;75:997-1002 Show less
