The aim of this thesis was to investigate the radiological phenotype of the human brain in familial longevity with regard to brain structure. This study was performed as part of the Leiden... Show moreThe aim of this thesis was to investigate the radiological phenotype of the human brain in familial longevity with regard to brain structure. This study was performed as part of the Leiden Longevity Study __ a study population consisting of offspring of long-lived Dutch people who are genetically predisposed to become long-lived as well and their environmentally and age-matched spouses. Dedicated MR imaging techniques were applied to study the phenotype of the human brain on the macrostructural as well as microstructural level. Both features which are most likely caused by early development and a lower susceptibility to known age-related structural brain changes on the macro- as well as microstructural level are hallmarks of the brain phenotype in longevity. The contributing mechanisms have yet to be identified but may involve homeostatic control and body function. Keeping in mind that there is a gradual transition from healthy brain aging to what is generally accepted as __normal__ brain aging and pathological brain changes as disease correlates, our study results implicate that the brains of offspring of nonagenarian siblings are less susceptible to neurodegenerative brain changes such as (vascular) dementia, Alzheimer__s disease and cerebrovascular disease. Our findings should be considered as starting points for future studies on the functional implications of the presented results and studies on the underlying pathways of brain structure preservation in human longevity. Show less
Altmann-Schneider, I.; Craen, A.J.M. de; Berg-Huysmans, A.A. van den; Slagboom, P.; Westendorp, R.G.J.; Buchem, M.A. van; Grond, J. van der 2015
BACKGROUND AND PURPOSE On MRI, cerebral white matter lesions, lacunar infarcts, and cerebral microbleeds are common imaging correlates of cerebral small vessel damage in apparently healthy elderly... Show moreBACKGROUND AND PURPOSE On MRI, cerebral white matter lesions, lacunar infarcts, and cerebral microbleeds are common imaging correlates of cerebral small vessel damage in apparently healthy elderly individuals. We investigated whether middle-aged to elderly offspring of nonagenarian siblings, who are predisposed to become long-lived as well, have a lower prevalence of white matter lesions, lacunar infarcts, and cerebral microbleeds than control subjects. METHODS All subjects were from the Leiden Longevity Study. In this study, middle-aged to elderly offspring of nonagenarian siblings, who are predisposed to become long-lived as well, were contrasted to their spouses. Cerebral small vessel disease was assessed using 3-T MRI. RESULTS Offspring were less likely to have severe periventricular frontal caps (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-1.1; P trend=0.01) and severe periventricular bands (OR, 0.4; 95% CI, 0.2-0.8; P trend=0.02). Moreover, offspring were less likely to have frontal (OR, 0.4; 95% CI, 0.2-0.9; P trend=0.05), parietal (OR, 0.4; 95% CI, 0.1-0.9; P trend=0.001), temporal (OR, 0.3; 95% CI, 0.1-0.8]; P trend=0.004), and occipital subcortical white matter lesions (OR, 0.3; 95% CI, 0.1-0.6; P trend=0.001). Prevalence of lacunar infarcts also was lower in offspring (OR, 0.3; 95% CI, 0.1-1.1; P=0.07). Prevalence of microbleeds was not significantly different in offspring and control subjects. CONCLUSIONS Exceptional familial longevity is associated with a lower susceptibility to white matter lesions and lacunar infarcts, but not cerebral microbleeds. Show less
Altmann-Schneider, I.; Craen, A.J.M. de; Slagboom, P.E.; Westendorp, R.G.J.; Buchem, M.A. van; Maier, A.B.; Grond, J. van der 2012
Background and Purpose-To investigate the prognostic value of cerebral microbleeds (CMB) regarding overall, cardiovascular-related, and stroke-related mortality and to investigate possible... Show moreBackground and Purpose-To investigate the prognostic value of cerebral microbleeds (CMB) regarding overall, cardiovascular-related, and stroke-related mortality and to investigate possible differences based on a cerebral amyloid angiopathy-type and nonlobar distribution of microbleeds. Methods-We included 435 subjects who were participants from the nested MRI substudy of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cox proportional hazard models were applied to estimate the risk of overall, cardiovascular-related, and stroke-related death associated with microbleeds in general and microbleeds with a lobar distribution suggestive of the presence of cerebral amyloid angiopathy. The corresponding Kaplan-Meier survival curves were calculated. Results-Subjects with >1 CMB had a 6-fold risk of stroke-related death compared to subjects without CMB (hazard ratio, 5.97; 95% CI, 1.60-22.26; P=0.01). The diagnosis of nonlobar microbleeds was associated with >2-fold risk of cardiovascular death compared to subjects without microbleeds (hazard ratio, 2.67; 95% CI, 1.23-5.81; P=0.01). Subjects with probable cerebral amyloid angiopathy-type microbleeds had >7-fold risk of stroke-related death compared to subjects without CMB (hazard ratio, 7.20; 95% CI, 1.44-36.10; P=0.02). Conclusions-This is the first study investigating the association between microbleeds and risk of overall, cardiovascular-related, and stroke-related mortality in an elderly population. Our findings indicate that the diagnosis of microbleeds is potentially of clinical relevance. Larger studies are needed to expand our observations and to address potential clinical implications and cost-benefits of such a policy. (Stroke. 2011;42:638-644.) Show less
Altmann-Schneider, I.; Trompet, S.; Craen, A.J.M. de; Es, A.C.G.M. van; Jukema, J.W.; Stott, D.J.; ... ; Grond, J. van der 2011
BACKGROUND AND PURPOSE: To investigate the prognostic value of cerebral microbleeds (CMB) regarding overall, cardiovascular-related, and stroke-related mortality and to investigate possible... Show moreBACKGROUND AND PURPOSE: To investigate the prognostic value of cerebral microbleeds (CMB) regarding overall, cardiovascular-related, and stroke-related mortality and to investigate possible differences based on a cerebral amyloid angiopathy-type and nonlobar distribution of microbleeds. METHODS: We included 435 subjects who were participants from the nested MRI substudy of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cox proportional hazard models were applied to estimate the risk of overall, cardiovascular-related, and stroke-related death associated with microbleeds in general and microbleeds with a lobar distribution suggestive of the presence of cerebral amyloid angiopathy. The corresponding Kaplan-Meier survival curves were calculated. RESULTS: Subjects with >1 CMB had a 6-fold risk of stroke-related death compared to subjects without CMB (hazard ratio, 5.97; 95% CI, 1.60-22.26; P=0.01). The diagnosis of nonlobar microbleeds was associated with >2-fold risk of cardiovascular death compared to subjects without microbleeds (hazard ratio, 2.67; 95% CI, 1.23-5.81; P=0.01). Subjects with probable cerebral amyloid angiopathy-type microbleeds had >7-fold risk of stroke-related death compared to subjects without CMB (hazard ratio, 7.20; 95% CI, 1.44-36.10; P=0.02). CONCLUSIONS: This is the first study investigating the association between microbleeds and risk of overall, cardiovascular-related, and stroke-related mortality in an elderly population. Our findings indicate that the diagnosis of microbleeds is potentially of clinical relevance. Larger studies are needed to expand our observations and to address potential clinical implications and cost-benefits of such a policy. Show less
