 |
|
Different Patterns of Cerebral Injury in Dementia With or Without Diabetes
Joshua A. Sonnen, MD;
Eric B. Larson, MD, MPH;
Kiri Brickell, MBChB;
Paul K. Crane, MD, MPH;
Randall Woltjer, MD, PhD;
Thomas J. Montine, MD, PhD;
Suzanne Craft, PhD
Arch Neurol. 2009;66(3):(doi:10.1001/archneurol.2008.579).
Background Diabetes mellitus (DM) increases the risk of dementia in the elderly. However, its underlying mechanisms, its connection with Alzheimer disease and vascular cognitive impairment, and effects of therapy remain unclear.
Objective To test the hypothesis that DM promotes specific neuropathologic processes that contribute to dementia and that these processes may be suppressed by antidiabetic therapy.
Design A comprehensive neuropathologic assessment of all cases from a community-based study of incident dementia (Adult Changes in Thought Study) that underwent autopsies (n = 259) and had information on DM status (n = 196). Biochemical analysis was conducted on a subset of these cases with rapidly frozen brain tissue (n = 57).
Participants Autopsy cases were divided into 4 groups: no DM/no dementia (DM–/dementia–), DM/no dementia (DM+/dementia–), no DM/dementia (DM–/dementia+), and DM/dementia (DM+/dementia+). Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnosis of dementia was assigned through a consensus of experts following biennial cognitive and physical evaluations. Diabetes was diagnosed based on information obtained from participants' extensive medical records.
Results In cases without dementia (n = 125), neuropathologic and biochemical end points did not differ significantly by DM status. However, we observed 2 patterns of injury in patients with dementia (n = 71) by their DM status. Individuals without DM but with dementia (DM–/dementia+) had a greater amyloid-β peptide load and increased levels of F2-isoprostanes in the cerebral cortex, while DM+/dementia+ patients had more microvascular infarcts and an increased cortical IL-6 (interleukin 6) concentration. The number of microvascular infarcts was greater in deep cerebral structures in patients with dementia whose diabetes was treated, whereas amyloid plaque load tended to be greater for untreated diabetic patients with dementia.
Conclusions These novel characterizations of 2 different patterns of cerebral injury in patients with dementia depending on DM status may have etiologic and therapeutic implications.
Published online: January 12, 2009 (doi:10.1001/archneur.2008.579).
Author Affiliations: Departments of Pathology (Drs Sonnen and Montine), Medicine (Dr Larson), and Psychiatry and Behavioral Sciences (Drs Brickell and Craft), University of Washington; Center for Health Studies, Group Health Cooperative (Drs Larson and Crane); and Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System (Dr Craft), Seattle; and Department of Pathology, Oregon Health & Sciences University, Portland (Dr Woltjer).
 CiteULike  Connotea  Delicious  Digg  Facebook  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
This Month in Archives of Neurology
Arch Neurol. 2009;66(3):298-299.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Neuropathologic evidence of endothelial changes in cerebral small vessel disease
Giwa et al.
Neurology 2012;78:167-174.
ABSTRACT
| FULL TEXT
Endothelial and inflammatory markers in relation to progression of ischaemic cerebral small-vessel disease and cognitive impairment: a 6-year longitudinal study in patients with type 2 diabetes mellitus
Umemura et al.
J. Neurol. Neurosurg. Psychiatry 2011;82:1186-1194.
ABSTRACT
| FULL TEXT
Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment
Bayer-Carter et al.
Arch Neurol 2011;68:743-752.
ABSTRACT
| FULL TEXT
Vascular risk factors and longitudinal changes on brain MRI: The ARIC study
Knopman et al.
Neurology 2011;76:1879-1885.
ABSTRACT
| FULL TEXT
Diabetes, Alzheimer disease, and vascular dementia: A population-based neuropathologic study
Ahtiluoto et al.
Neurology 2010;75:1195-1202.
ABSTRACT
| FULL TEXT
Cognitive decline: the relevance of diabetes, hyperlipidaemia and hypertension
Etgen et al.
British Journal of Diabetes & Vascular Disease 2010;10:115-122.
ABSTRACT
Jassal et al. Respond to "Microalbuminuria and Brain Vascular Disease"
Jassal et al.
Am J Epidemiol 2010;171:290-291.
FULL TEXT
Advances in Vascular Cognitive Impairment
Gorelick and Bowler
Stroke 2010;41:e93-e98.
FULL TEXT
Pathophysiology of cognitive dysfunction in older people with type 2 diabetes: vascular changes or neurodegeneration?
Umegaki
Age Ageing 2010;39:8-10.
ABSTRACT
| FULL TEXT
Risk of dementia hospitalisation associated with cardiovascular risk factors in midlife and older age: the Atherosclerosis Risk in Communities (ARIC) study
Alonso et al.
J. Neurol. Neurosurg. Psychiatry 2009;80:1194-1201.
ABSTRACT
| FULL TEXT
Diabetes is associated with a slower rate of cognitive decline in Alzheimer disease
Sanz et al.
Neurology 2009;73:1359-1366.
ABSTRACT
| FULL TEXT
Effects of Diabetes and Adiposity on Cognition in Elders
JWatch Neurology 2009;2009:2-2.
FULL TEXT
The Role of Metabolic Disorders in Alzheimer Disease and Vascular Dementia: Two Roads Converged
Craft
Arch Neurol 2009;66:300-305.
ABSTRACT
| FULL TEXT
|
