Risk of Dementia in Type 2 Diabetes-Related Retinal Disease

Persons with diabetes and severe diabetic retinal disease are at increased risk for dementia, a new study has found. In a longitudinal cohort study of 29,961 patients with type 2 diabetes who were aged ≥60 years, researchers found that those patients with diabetic retinal disease (n=2008; 6.8%) at baseline had a 42% increased risk of incident dementia (sociodemographics-adjusted hazard ratio [HR] = 1.42; 95% confidence interval [CI], 1.27-1.58). Upon further adjustment for diabetes-specific (eg, diabetes duration, pharmacotherapy, HbA1c, hypoglycemia, and hyperglycemia) and vascular-related (eg, vascular disease, smoking history, and body mass index) disease conditions, results saw only a small change (HR, 1.29; 95% CI 1.14-1.45 and HR, 1.35; 95% CI 1.21-1.52, respectively). Researchers used electronic medical records for the collection of data including diagnoses and treatment of severe diabetic retinal disease (specifically, diabetic proliferative retinopathy and macular edema) between the years 1996-1998, and of dementia diagnoses for the subsequent 10 years (1998-2008).¹

In recent years, a growing body of evidence suggests that vascular risk factors, such as hypertension, high cholesterol, and diabetes, can contribute to the onset or course of Alzheimer’s disease.² One longitudinal study of 16,667 older patients (>65 years) with type 2 diabetes found a greater risk of dementia among those with a history of severe hypoglycemia.³ Low blood pressure has also been linked to cognitive decline and dementia in older adults.² Similarly, the association between type 2 diabetes and increased risk of dementia has been reported, but the etiology of this increased risk has remained unclear. It has been hypothesized that cerebral microvascular disease may be the causal link in this association. Cerebral microvascular disease, or small-vessel disease, refers to a group of pathological processes with different etiologies, affecting the small arteries, arterioles, venules, and capillaries in the brain. The most common forms are age-related and hypertension-related arteriolosclerosis and cerebral amyloid angiopathy.² Some research has suggested that diminished flow of blood and nutrients to the brain due to thickening of the microvessel walls can lead to the destabilization of neurons, synapses, neurotransmission, and cognitive function – thus creating the neurodegenerative state that encompasses formation of plaques, neurofibrillary tangles, and in some cases, Lewy bodies.^4,5 Based on similarities in the anatomical and physiologic features of cerebral and retinal microvessels, the investigators of this study examined the link between diabetic retinal disease and dementia in type 2 diabetes.

The authors concluded that diabetic patients with severe retinal disease are at increased risk for dementia, which may reflect a causal link between microvascular disease and dementia.¹

References

1. Exalto LG, Biessels GJ, Karter AJ, Huang ES, Quesenberry Jr CP, Whitmer RA. Severe diabetic retinal disease and dementia risk in type 2 diabetes. J Alzheimers Dis.  Published online ahead of print March 13, 2014.
2. Sierra C. Cerebral small vessel disease, cognitive impairment and vascular dementia. Panminerva Med. 2012 Sep;54(3):179-88.
3. Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009;301(15):1565-1572.
4. de la Torre JC. Cerebromicrovascular pathology in Alzheimer's disease compared to normal aging. Gerontology. 1997;43(1-2):26-43.
5. de la Torre JC, Stefano GB. Evidence that Alzheimer's disease is a microvascular disorder: the role of constitutive nitric oxide. Brain Res Brain Res Rev. 2000;34(3):119-136.