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Letters to the Editor |

Diabetes Mellitus and Alzheimer Disease

Kathleen S. N. Franco, MD; David Bronson, MD
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Copyright 2005 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

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Arch Neurol. 2005;62(2):330-330. doi:10.1001/archneur.62.2.330-a
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We read with interest the article by Dr Arvanitakis and colleagues whose prospective study reports an association between diabetes mellitus and an increased risk for Alzheimer Disease (AD),1 as well as more rapid decline in perceptual speed. Excellent cognitive testing also identified that persons with diabetes mellitus in their sample started with lower baseline scores in multiple areas of cognition and memory.

We were curious if patients with depression were excluded in the current study, particularly since prevalence rates of depression in patients with diabetes mellitus (15%-20%) run much higher than for aged matched controls. We noted Dr Wilson has written about depression, cognitive decline, and the risk of developing AD.2 Others support that finding and now there are data indicating that persons with depression are at an increased risk to develop diabetes mellitus.3 4

Since depression reduces the speed of cognitive processing, as well as the ability to remember, it would be important to know if there were patients included who were depressed prior to their onset of diabetes. This would partially explain why they started at lower cognitive levels or if there were some who became depressed after diabetes mellitus was diagnosed, potentially reducing perceptual speed.

In the discussion, the authors “raise the possibility that cerebral infarctions mediate the association between diabetes mellitus with AD.” We agree that “many people with cerebral infarcts do not experience clinical strokes,” and also that cerebral infarctions are preferentially associated with reduced perceptual speed.5 Individuals who do not develop depression until late in life are also quite likely to have increased evidence of vascular pathology on brain imagery with no reports of experiencing a clinical stroke.6 Patients without diabetes mellitus who have depression are more likely to have hyperglycemia, higher hemoglobin AIC levels, and hyperinsulinemia.7

Some have proposed “stress-related cortisol secretion,” clearly identified with depression, as a connecting link to endocrine, metabolic, and hemodynamic abnormalities, as well as obesity.8 9

Your discussion also brought out the possibility that hippocampal synaptic plasticity might be associated with greater risk of patients having diabetes mellitus to develop AD. Reduced hippocampal volume is described with both untreated depression10 and incident dementia in patients with geriatric depression.11

We have no doubt that having diabetes mellitus puts one at greater risk for AD, but that mood might play an even stronger role in both.

AUTHOR INFORMATION

Correspondence: Dr Franco, Cleveland Clinic Foundation, 9500 Euclid Ave, P57, Cleveland, OH 44195 (francok@ccf.org).

REFERENCES

Arvanitakis  Z, Wilson  RS, Bienias  JL.  et al.  Diabetes mellitus and risk of alzheimer disease and decline in cognitive function. Arch Neurol 2004;61661- 666
PubMed
Wilson  RS, Barnes  LL, Mendes de Leon  CF.  et al.  Depressive symptoms, cognitive decline and risk of AD in older persons. Neurology 2002;59364- 370
PubMed
Schneider  JA, Wilson  RS, Cochran  EJ.  et al.  Relation of cerebral infarctions to dementia and cognitive function in older persons. Neurology 2003;601082- 1088
PubMed
Berger  AK, Fratiglioni  L, Forsell  Y.  et al.  The occurrence of depressive symptoms in the preclinical phase of AD: a population-based study. Neurology 1999;531998- 2002
PubMed
Morris  JC, Heyman  A, Mohs  RC.  et al.  The consortium to establish a registry for Alzheimer Disease (CERAD), part I. Neurology 1989;391159- 1165
PubMed
Saydah  SH, Brancati  FL, Golden  SH.  et al.  Depressive symptoms and the risk of type 2 diabetes mellitus in a US sample. Diabetes Metab Res Rev 2003;19202- 208
PubMed
Tiemeier  H. Biological risk factors for late life depression. Eur J Epidemiol 2003;18745- 750
PubMed
Rubio  A, Vestner  AL, Stewart  JM.  et al.  Suicide and Alzheimer pathology in the elderly: a case-control study. Biol Psychiatry 2001;49137- 145
PubMed
Stunkard  AJ, Faith  MS, Allison  KC. Depression and obesity. Biol Psychiatry 2003;54330- 337
PubMed
Sheline  YI, Gado  MH, Kraemer  HC. Untreated depression and hippocampal volume loss. Am J Psychiatry 2003;1601516- 1518
PubMed
Steffens  DC, Payne  ME, Greenberg  DL. Hippocampal volume and incident in geriatric depression. Am J Geriatr Psychiatry 2002;1062- 71
PubMed

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Arvanitakis  Z, Wilson  RS, Bienias  JL.  et al.  Diabetes mellitus and risk of alzheimer disease and decline in cognitive function. Arch Neurol 2004;61661- 666
PubMed
Wilson  RS, Barnes  LL, Mendes de Leon  CF.  et al.  Depressive symptoms, cognitive decline and risk of AD in older persons. Neurology 2002;59364- 370
PubMed
Schneider  JA, Wilson  RS, Cochran  EJ.  et al.  Relation of cerebral infarctions to dementia and cognitive function in older persons. Neurology 2003;601082- 1088
PubMed
Berger  AK, Fratiglioni  L, Forsell  Y.  et al.  The occurrence of depressive symptoms in the preclinical phase of AD: a population-based study. Neurology 1999;531998- 2002
PubMed
Morris  JC, Heyman  A, Mohs  RC.  et al.  The consortium to establish a registry for Alzheimer Disease (CERAD), part I. Neurology 1989;391159- 1165
PubMed
Saydah  SH, Brancati  FL, Golden  SH.  et al.  Depressive symptoms and the risk of type 2 diabetes mellitus in a US sample. Diabetes Metab Res Rev 2003;19202- 208
PubMed
Tiemeier  H. Biological risk factors for late life depression. Eur J Epidemiol 2003;18745- 750
PubMed
Rubio  A, Vestner  AL, Stewart  JM.  et al.  Suicide and Alzheimer pathology in the elderly: a case-control study. Biol Psychiatry 2001;49137- 145
PubMed
Stunkard  AJ, Faith  MS, Allison  KC. Depression and obesity. Biol Psychiatry 2003;54330- 337
PubMed
Sheline  YI, Gado  MH, Kraemer  HC. Untreated depression and hippocampal volume loss. Am J Psychiatry 2003;1601516- 1518
PubMed
Steffens  DC, Payne  ME, Greenberg  DL. Hippocampal volume and incident in geriatric depression. Am J Geriatr Psychiatry 2002;1062- 71
PubMed

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