Different patterns of cerebral injury in dementia with or without diabetes

Joshua A. Sonnen, Eric B. Larson, Kiri Brickell, Paul K. Crane, Randall (Randy) Woltjer, Thomas J. Montine, Suzanne Craft

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)315-322
Number of pages8
JournalArchives of Neurology
Volume66
Issue number3
DOIs
StatePublished - Mar 2009

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Dementia
Diabetes Mellitus
Wounds and Injuries
Diabetes
Autopsy
F2-Isoprostanes
Amyloid Plaques
Hypoglycemic Agents
Amyloid
Diagnostic and Statistical Manual of Mental Disorders
Cerebral Cortex
Medical Records
Blood Vessels
Interleukin-6

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Sonnen, J. A., Larson, E. B., Brickell, K., Crane, P. K., Woltjer, R. R., Montine, T. J., & Craft, S. (2009). Different patterns of cerebral injury in dementia with or without diabetes. Archives of Neurology, 66(3), 315-322. https://doi.org/10.1001/archneurol.2008.579

Different patterns of cerebral injury in dementia with or without diabetes. / Sonnen, Joshua A.; Larson, Eric B.; Brickell, Kiri; Crane, Paul K.; Woltjer, Randall (Randy); Montine, Thomas J.; Craft, Suzanne.

In: Archives of Neurology, Vol. 66, No. 3, 03.2009, p. 315-322.

Research output: Contribution to journalArticle

Sonnen, JA, Larson, EB, Brickell, K, Crane, PK, Woltjer, RR, Montine, TJ & Craft, S 2009, 'Different patterns of cerebral injury in dementia with or without diabetes', Archives of Neurology, vol. 66, no. 3, pp. 315-322. https://doi.org/10.1001/archneurol.2008.579
Sonnen, Joshua A. ; Larson, Eric B. ; Brickell, Kiri ; Crane, Paul K. ; Woltjer, Randall (Randy) ; Montine, Thomas J. ; Craft, Suzanne. / Different patterns of cerebral injury in dementia with or without diabetes. In: Archives of Neurology. 2009 ; Vol. 66, No. 3. pp. 315-322.
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