Comorbidity of Cerebrovascular and Alzheimer's Disease in Aging.

BACKGROUND Cerebrovascular disease often coexists with Alzheimer's disease (AD). While both diseases share common risk factors, their interrelationship remains unclear. Increasing the understanding of how cerebrovascular changes interact with AD is essential to develop therapeutic strategies and refine biomarkers for early diagnosis. OBJECTIVE We investigate the prevalence and risk factors for the comorbidity of amyloid-β (Aβ) and cerebrovascular disease in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing, and further examine their cross-sectional association. METHODS A total of 598 participants (422 cognitively normal, 89 with mild cognitive impairment, 87 with AD) underwent positron emission tomography and structural magnetic resonance imaging for assessment of Aβ deposition and cerebrovascular disease. Individuals were categorized based on the comorbidity status of Aβ and cerebrovascular disease (V) as Aβ-V-, Aβ-V+, Aβ+V-, or Aβ+V+. RESULTS Advancing age was associated with greater likelihood of cerebrovascular disease, high Aβ load and their comorbidity. Apolipoprotein E ɛ4 carriage was only associated with Aβ positivity. Greater total and regional WMH burden were observed in participants with AD. However, no association were observed between Aβ and WMH measures after stratification by clinical classification, suggesting that the observed association between AD and cerebrovascular disease was driven by the common risk factor of age. CONCLUSION Our observations demonstrate common comorbid condition of Aβ and cerebrovascular disease in later life. While our study did not demonstrate a convincing cross-sectional association between Aβ and WMH burden, future longitudinal studies are required to further confirm this.

[1]  C. Rowe,et al.  Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s disease , 2019, Alzheimer's Research & Therapy.

[2]  C. Rowe,et al.  Influence of Comorbidity of Cerebrovascular Disease and Amyloid-β on Alzheimer's Disease. , 2019, Journal of Alzheimer's disease : JAD.

[3]  Nick A. Weaver,et al.  Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions , 2019, Neurobiology of Aging.

[4]  Robert I. Reid,et al.  Amyloid, Vascular, and Resilience Pathways Associated with Cognitive Aging , 2019, Annals of neurology.

[5]  C. Jack,et al.  White matter hyperintensities: relationship to amyloid and tau burden. , 2019, Brain : a journal of neurology.

[6]  C. Rowe,et al.  A Polygenic Risk Score Derived From Episodic Memory Weighted Genetic Variants Is Associated With Cognitive Decline in Preclinical Alzheimer’s Disease , 2018, Front. Aging Neurosci..

[7]  Pierrick Coupé,et al.  MRI white matter lesion segmentation using an ensemble of neural networks and overcomplete patch-based voting , 2018, Comput. Medical Imaging Graph..

[8]  Olivier Salvado,et al.  Implementing the centiloid transformation for 11C-PiB and β-amyloid 18F-PET tracers using CapAIBL , 2018, NeuroImage.

[9]  P. Sachdev,et al.  Neuroimaging and neuropathology indices of cerebrovascular disease burden , 2018, Neurology.

[10]  Ludovica Griffanti,et al.  Classification and characterization of periventricular and deep white matter hyperintensities on MRI: A study in older adults , 2017, NeuroImage.

[11]  W. M. van der Flier,et al.  Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline , 2017, Alzheimer's Research & Therapy.

[12]  Sandra E. Black,et al.  Associations between amyloid β and white matter hyperintensities: A systematic review , 2017, Alzheimer's & Dementia.

[13]  David A. Bennett,et al.  White matter hyperintensities, incident mild cognitive impairment, and cognitive decline in old age , 2016, Annals of clinical and translational neurology.

[14]  P. Vemuri,et al.  The role of cerebrovascular disease when there is concomitant Alzheimer disease. , 2016, Biochimica et biophysica acta.

[15]  K. Blennow,et al.  Cerebral white matter lesions – associations with Aβ isoforms and amyloid PET , 2016, Scientific Reports.

[16]  H. Feldman,et al.  Periventricular hyperintensities are associated with elevated cerebral amyloid , 2016, Neurology.

[17]  P. Snyder,et al.  Sensitivity of composite scores to amyloid burden in preclinical Alzheimer's disease: Introducing the Z-scores of Attention, Verbal fluency, and Episodic memory for Nondemented older adults composite score , 2015, Alzheimer's & dementia.

[18]  Paul M. Thompson,et al.  Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly , 2015, Front. Aging Neurosci..

[19]  C. Rowe,et al.  Comparison of MR-less PiB SUVR quantification methods , 2015, Neurobiology of Aging.

[20]  C. Jack,et al.  Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly , 2015, Brain : a journal of neurology.

[21]  Robert A. Koeppe,et al.  The Centiloid Project: Standardizing quantitative amyloid plaque estimation by PET , 2015, Alzheimer's & Dementia.

[22]  A. Brickman,et al.  Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community. , 2012, Archives of neurology.

[23]  W. Jagust,et al.  Vascular burden and Alzheimer disease pathologic progression , 2012, Neurology.

[24]  Evan Fletcher,et al.  Coevolution of white matter hyperintensities and cognition in the elderly , 2012, Neurology.

[25]  Cindee M. Madison,et al.  Cerebrovascular disease, beta-amyloid, and cognition in aging , 2012, Neurobiology of Aging.

[26]  Owen Carmichael,et al.  Longitudinal changes in white matter disease and cognition in the first year of the Alzheimer disease neuroimaging initiative. , 2010, Archives of neurology.

[27]  E. Salmon,et al.  18F‐flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: A phase 2 trial , 2010, Annals of neurology.

[28]  C. Rowe,et al.  Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging , 2010, Neurobiology of Aging.

[29]  H. Markus,et al.  The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis , 2010, BMJ : British Medical Journal.

[30]  James Robert Brašić,et al.  In Vivo Imaging of Amyloid Deposition in Alzheimer Disease Using the Radioligand 18F-AV-45 (Flobetapir F 18) , 2010, Journal of Nuclear Medicine.

[31]  C. Rowe,et al.  The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease , 2009, International Psychogeriatrics.

[32]  O. Lopez,et al.  Cerebral Infarcts and Cognitive Performance: Importance of Location and Number of Infarcts , 2009, Stroke.

[33]  Jennifer L. Whitwell,et al.  Hippocampal volumes, proton magnetic resonance spectroscopy metabolites, and cerebrovascular disease in mild cognitive impairment subtypes. , 2008, Archives of neurology.

[34]  J. MacFall,et al.  Classification of White Matter Lesions on Magnetic Resonance Imaging in Elderly Persons , 2008, Biological Psychiatry.

[35]  Eric E. Smith,et al.  Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia. , 2008, Archives of neurology.

[36]  David A. Bennett,et al.  Mixed brain pathologies account for most dementia cases in community-dwelling older persons , 2007, Neurology.

[37]  K. Jellinger,et al.  Prevalence and impact of cerebrovascular pathology in Alzheimer's disease and parkinsonism , 2006, Acta neurologica Scandinavica.

[38]  K. Jellinger,et al.  Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer disease , 2005, Journal of the Neurological Sciences.

[39]  W. Markesbery,et al.  AD lesions and infarcts in demented and non‐demented Japanese‐American men , 2005, Annals of neurology.

[40]  J. Schneider,et al.  Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology , 2004, Neurology.

[41]  M. Breteler,et al.  Vascular risk factors for Alzheimer’s disease: An epidemiologic perspective , 2000, Neurobiology of Aging.

[42]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[43]  J. Haxby,et al.  The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults , 1995, Neurology.

[44]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.