Article

Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study.

Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Neurology (Impact Factor: 8.3). 09/2010; 75(13):1195-202. DOI: 10.1212/WNL.0b013e3181f4d7f8
Source: PubMed

ABSTRACT To investigate the relation of diabetes to dementia, Alzheimer disease (AD), and vascular dementia (VaD), through analyses of incidence, mortality, and neuropathologic outcomes in a prospective population-based study of the oldest old.
The Vantaa 85+ study included 553 residents living in the city of Vantaa, Finland, and aged ≥85 years on April 1, 1991. Survivors were reexamined in 1994, 1996, 1999, and 2001. Autopsies were performed in 291 persons who died during the follow-up (48% of total population). Diabetes was assessed according to self-report, medical record of physician-diagnosed diabetes, or use of antidiabetic medication. Macroscopic infarcts were identified from 1-cm coronal slices of cerebral hemispheres, 5-mm transverse brainstem slices, and sagittal cerebellum slices. Methenamine silver staining was used for β-amyloid, methenamine silver-Bodian staining for neurofibrillary tangles, and modified Bielschowsky method for neuritic plaques. Cox proportional hazards and multiple logistic regression models were used to analyze the association of diabetes with dementia and neuropathology, respectively.
Diabetes at baseline doubled the incidence of dementia, AD, and VaD, and increased mortality. Individuals with diabetes were less likely to have β-amyloid (hazard ratio [HR] [95% confidence interval (CI)] was 0.48 [0.23-0.98]) and tangles (HR [95% CI] 0.72 [0.39-1.33]) but more likely to have cerebral infarcts (HR [95% CI] 1.88 [1.06-3.34]) after all adjustments.
Elderly patients with diabetes develop more extensive vascular pathology, which alone or together with AD-type pathology (particularly in APOE ε4 carriers) results in increased dementia risk.

0 Bookmarks
 · 
130 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer’s disease (AD) is the most common neurodegenerative cause of dementia in the elderly. AD is accompanied by the accumulation of amyloid peptides in the brain parenchyma and in the cerebral vessels. The sporadic form of AD accounts for about 95% of all cases. It is characterized by a late onset, typically after the age of 65, with a complex and still poorly understood aetiology. Several observations point towards a central role of cerebrovascular dysfunction in the onset of sporadic AD (SAD). According to the “vascular hypothesis”, AD may be initiated by vascular dysfunctions that precede and promote the neurodegenerative process. In accordance to this, AD patients show increased hemorrhagic or ischemic stroke risks. It is now clear that multiple bidirectional connections exist between AD and cerebrovascular disease, and in this new scenario, the effect of amyloid peptides on vascular cells and blood platelets appear to be central to AD. In this review, we analyze the effect of amyloid peptides on vascular function and platelet activation and its contribution to the cerebrovascular pathology associated with AD and the progression of this disease.
    Frontiers in Cellular Neuroscience 03/2015; DOI:10.3389/fncel.2015.00065 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Major depressive disorder (MDD) and diabetes mellitus (DM) have reciprocal relationships and share common pathophysiological mechanisms in the central nervous system. Depression and diabetes negatively affect cognitive function and are independent risk factors for mild cognitive impairment and Alzheimer's disease (AD). It has been hypothesized that alterations in the production and processing of amyloid beta (Aβ) may be the principal pathological process in AD. Furthermore, it has been increasingly demonstrated that a long preclinical course precedes AD. A derivative of this observation is the hypothesis that a convergent pathophysiological substrate subserving MDD and DM may promote beta amyloid (Aβ) deposition. The present paper will review evidence linking MDD and DM to Aβ accumulation, with a particular emphasis on original reports that report on levels of Aβ40, Aβ42 and the Aβ40/42 ratio in plasma, serum, or cerebrospinal fluid of individuals with MDD and DM. The overarching goal herein is to press the point that MDD and DM are amyloidogenic and consequently represent modifiable risk factors for AD in later life. The prognostic intervention and prevention opportunity suggested by this notion is that: 1) increased rates of mood disorders and DM in an aging population will increase the population attributable risk for AD ascribed to these conditions, 2) improved outcomes in mood disorders and DM by effective ``treating to target`` may exert a salutary influence on underlying dementia promoting processes, 3) novel and repurposed medications that are capable of normalizing pathophysiological processes in MDD and DM could decrease the vulnerability towards AD.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 11/2014; 13(10). · 2.70 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes mellitus is associated with an increase in the risk of dementia and the proportion of patients who convert from mild cognitive impairment (MCI) to dementia. In addition to MCI and dementia, the stages of diabetes-associated cognitive dysfunction include subtle cognitive changes that are unlikely to affect activities of daily life or diabetes self-management. These diabetes-associated cognitive decrements have structural brain correlates detectable with brain MRI, but usually show little progression over time. Although cognitive decrements do not generally represent a pre-dementia stage in patients below the age of 60-65 years, in older individuals these subtle cognitive changes might represent the earliest stages of a dementia process. Acknowledgment of diabetes-associated cognitive decrements can help to improve understanding of patients' symptoms and guide management. Future challenges are to establish the importance of screening for cognitive impairment in people with diabetes, to identify those at increased risk of accelerated cognitive decline at an early stage, and to develop effective treatments. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Neurology 03/2015; 14(3):329-40. DOI:10.1016/S1474-4422(14)70249-2 · 21.82 Impact Factor

Full-text (2 Sources)

Download
10 Downloads
Available from
Sep 17, 2014