Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Apr;70(4):488-95.
doi: 10.1001/2013.jamaneurol.405.

The aging brain and cognition: contribution of vascular injury and aβ to mild cognitive dysfunction

Natalie L Marchant  1 , Bruce R Reed, Nerses Sanossian, Cindee M Madison, Stephen Kriger, Roxana Dhada, Wendy J Mack, Charles DeCarli, Michael W Weiner, Dan M Mungas, Helena C Chui, William J Jagust
Affiliations

The aging brain and cognition: contribution of vascular injury and aβ to mild cognitive dysfunction

Natalie L Marchant et al. JAMA Neurol. 2013 Apr.

Abstract

Importance: β-Amyloid (Aβ) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI's influence on cognition and clinical impairment, separate from and in conjunction with pathologic changes associated with Alzheimer disease (AD).

Objective: To examine the relationship between neuroimaging measures of VBI and brain Aβ deposition and their associations with cognition.

Design and setting: A cross-sectional study in a community- and clinic-based sample recruited for elevated vascular disease risk factors.

Participants: Clinically normal (mean age, 77.1 years [N = 30]), cognitively impaired (mean age, 78.0 years [N = 24]), and mildly demented (mean age, 79.8 years [N = 7]) participants.

Interventions: Magnetic resonance imaging, Aβ (Pittsburgh Compound B-positron emission tomographic [PiB-PET]) imaging, and cognitive testing.

Main outcome measures: Magnetic resonance images were rated for the presence and location of infarct (34 infarct-positive participants, 27 infarct-negative participants) and were used to quantify white matter lesion volume. The PiB-PET uptake ratios were used to create a PiB index by averaging uptake across regions vulnerable to early Aβ deposition; PiB positivity (29 PiB-positive participants, 32 PiB-negative participants) was determined from a data-derived threshold. Standardized composite cognitive measures included executive function and verbal and nonverbal memory.

Results: Vascular brain injury and Aβ were independent in both cognitively normal and impaired participants. Infarction, particularly in cortical and subcortical gray matter, was associated with lower cognitive performance in all domains (P < .05 for all comparisons). Pittsburgh Compound B positivity was neither a significant predictor of cognition nor interacted with VBI.

Conclusions and relevance: In this elderly sample with normal cognition to mild dementia, enriched for vascular disease, VBI was more influential than Aβ in contemporaneous cognitive function and remained predictive after including the possible influence of Aβ. There was no evidence that VBI increases the likelihood of Aβ deposition. This finding highlights the importance of VBI in mild cognitive impairment and suggests that the impact of cerebrovascular disease should be considered with respect to defining the etiology of mild cognitive impairment.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Weiner reports (for 2010–2012) having served on scientific advisory boards for Eli Lilly & Company, Araclon and Institut Catala de Neurociencies Aplicades, the Research Advisory Committee on Gulf War Veterans’ Illnesses, Biogen Idec, and Pfizer Inc; having served as a consultant for AstraZeneca, Araclon, Medivation/Pfizer Inc, Ipsen, TauRx Therapeutics Ltd, Bayer Healthcare, Biogen Idec, Exonhit Therapeutics SA, Servier, Synarc, Janssen, Harvard University, and KLJ Associates; having received travel funds from NeuroVigil, Inc, CHRU-Hopital Roger Salengro, Siemens, AstraZeneca, Geneva University Hospitals, Eli Lilly & Company, University of California, San Diego–Alzheimer’s Disease Neuroimaging Initiative (ADNI), Paris University, Institut Catala de Neurociencies Aplicades, University of New Mexico School of Medicine, Ipsen, Clinical Trials on Alzheimer’s Disease, Pfizer Inc, the AD/PD meeting (Conference on Alzheimer’s and Parkinson’s Diseases), Paul Sabatier University, Novartis, Tohoku University, Fundacio ACE, and Travel eDreams, Inc; having served on the editorial advisory boards of Alzheimer’s & Dementia and Magnetic Resonance Imaging; having received honoraria from NeuroVigil, Inc, Institute Catala de Neurociencies Aplicades, PMDA (Pharmaceuticals and Medical Devices Agency)/Japanese Ministry of Health, Labour, and Welfare, Tohoku University, and Alzheimer’s Drug Discovery Foundation; having received commercial entities research support from Merck and Avid; having received government entities research support from the Department of Defense and the Department of Veterans Affairs; and owning stock options in Synarc and Elan. Dr Weiner also reports that the following organizations contributed to the Foundation for the National Institutes of Health and thus to the National Institute on Aging–funded ADNI: Abbott, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Anonymous Foundation, AstraZeneca, Bayer Healthcare, BioClinica, Inc (ADNI 2), Bristol-Myers Squibb, Cure Alzheimer’s Fund, Eisai, Elan, Gene Network Sciences, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly & Company, Medpace, Merck, Novartis, Pfizer Inc, Roche, Schering Plough, Synarc, and Wyeth.

Figures

Figure
Figure
Scatterplot of Global Pittsburgh Compound B (PiB) Index volume stratified by infarct presence and location. Black bars represent mean Global PiB Index for infarct groups. The dichotomous categorization of Global PiB Index (PiB+/−) is shown by the dashed line. Circles represent clinical status of individuals: white, normal (Clinical Dementia Rating [CDR] = 0); gray, impaired (CDR ≥ 0.5).
See this image and copyright information in PMC

References

    1. Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69(24):2197–2204. - PubMed
    1. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270–279. - PMC - PubMed
    1. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–269. - PMC - PubMed
    1. Mintun MA, Larossa GN, Sheline YI, et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006;67 (3):446–452. - PubMed
    1. Rowe CC, Ng S, Ackermann U, et al. Imaging 3-amyloid burden in aging and dementia. Neurology. 2007;68(20):1718–1725. - PubMed

Publication types

MeSH terms