Diabetic Cognitive Impairment: Need for Consensus Guidelines for Diagnosis

Dear Editor, Diabetes has been known for its crucial bidirectional association with dementia. Dementia, including mild cognitive impairment (MCI), significantly impairs self-management skills in patients with diabetes and influences physicians' decision-making regarding therapy choice and glycemic goals.1 The recent international guidelines have underscored the importance of assessing the cognitive status of patients with diabetes. The American Diabetes Association recommends screening for cognitive impairment, especially in elderly, very young, or other vulnerable individuals, using standard neuropsychological tools.2 Diagnosing dementia in diabetes poses challenges due to multifaceted constraints. Implementing cognitive assessments in busy diabetic clinics is time-consuming, and diagnosing specific types of dementia requires adherence to specific criteria. In the field of diabetes and cognition, terms, such as "diabetic cognitive impairment" (DCI), "diabetic dementia," and "cognitive dysfunction caused by diabetes," have been introduced.3-5 However, to date, there is no consensus on diagnostic criteria for DCI, that is, cognitive dysfunction exclusively attributed to diabetes. Research studies utilizing inconsistent diagnostic criteria have led to ambiguous findings, as diabetes is a risk factor for both Alzheimer's disease (AD) and vascular dementia (VaD).6 Other independent risk factors for dementia include gender, marital status, literacy level, addiction, vascular, and neuroticism. In dementia patients, ruling out numerous confounders becomes nearly impossible without applying strict patient selection criteria. There are also concerns regarding the assessment tools to evaluate cognition, which require linguistic adaptations and adjustments to the scoring system based on literacy status. The pattern of cognitive dysfunctions observed in various studies is nonspecific, likely due to diverse populations with different risk factors. Imaging characteristics further complicate the scenario. Although small vessel changes are common in diabetes, their presence alone does not necessarily lead to cognitive impairment. Extensive small vessel changes do not provide a definitive marker to distinguish whether they are solely due to diabetes or VaD. Moreover, in the elderly, nonspecific changes on T2-weighted magnetic resonance imaging (MRI), sometimes resembling small vessel changes, are frequent,7 and these may not be attributable to diabetes or small vessel-related cognitive impairments. In addition, in demented diabetic patients without apparent changes in imaging, it is not possible to directly attribute the cognitive deficits to diabetes due to the presence of multiple confounders simultaneously. Advanced imaging that might specifically identify DCI, such as amyloid positron emission tomography (PET) for AD, is still not available. Furthermore, diabetes can obscure the interpretation of brain PET scans unlike AD or Parkinson's Disease-MCI (PD-MCI), there are currently no surrogate biomarkers in brain serum to diagnose DCI. Therefore, there is an urgent need for consensus guidelines to define and diagnose DCI accurately. Future research should identify specific patterns of cognitive dysfunction associated with DCI. Before attributing cognitive, behavioral, and psychiatric morbidities to diabetes, careful selection of subjects with control for confounders other than diabetes is essential. It must be definitively established that cognitive impairment occurs post-diabetes diagnosis, although excluding pre-existing conditions remains challenging. Studies are needed to explore imaging characteristics linked to DCI, if any. We advocate for consensus on whether a normal MRI should be a primary inclusion criterion in future studies to eliminate multiple confounders. Advanced imaging, such as functional MRI, could aid in identifying potential anatomical substrates related to DCI. Finally, there is a critical need for biomarkers to diagnose DCI effectively. In conclusion, there is a significant journey ahead before we can assert with sufficient certainty whether an individual is suffering from DCI rather than dementia compounded by diabetes. We propose a set of preliminary diagnostic criteria for DCI (Box 1). Future studies must be approached with clarity of thought, depth, precise diagnostic criteria, and rigorous patient selection to prevent the perpetuation of ambiguities surrounding DCI. Otherwise, research may lead to misleading results complicating clinical interpretation and management further.Box 1: Proposed diagnostic criteria for DCIAuthor contributions SD generated the idea. SD and SC conjointly wrote the first draft, which was further edited by RG and RB. All authors agreed upon the final version of the manuscript. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.