EARLY RADIOLOGICAL BIOMARKERS OF COGNITIVE DECLINE IN INTERNAL MEDICINE PATIENTS WITH CARDIO METABOLIC DISORDERS
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Keywords
Cognitive Decline, Hippocampal Atrophy, White Matter Hyperintensities, Cardiometabolic Disorders, Brain Age Gap
Abstract
In the elderly populations, cognitive decline has been suggested to be a multifactorial condition, especially in patients with co-morbid cardiometabolic risk factors, such as diabetes, hypertension and dyslipidaemia. This study sought out early radiological biomarkers for cognitive impairment in internal medicine patients with these disorders. Previous works have linked hippocampal atrophy, white matter hyperintensities (WMHs), cerebral small vessel disease (CSVD), and abnormal Default Mode Network (DMN) connectivity with declining cognitive status, particularly in metabolic and vascular risk population profiles. The study was carried out as a cross-sectional analytical study at Jinnah Postgraduate Medical Centre, Karachi on 246 patients with diagnosis of cardiometabolic disorders in the internal medicine. All subjects were assessed using standard neuropsychological tests to determine presence or absence of cognitive impairment. All participants received high-resolution brain MRI acquisition (T1-weighted volumetric imaging and resting-state functional MRI). Quantitative measurements included hippocampus volume, burden of WMHs and CSVD markers and DMN connectivity, but implemented locally at JPMC. As an additional neuroimaging metric, the models for prediction of the brain age were used to calculate the Brain Age Gap (BAG). Findings were that those with cognitive impairment had both significantly smaller hippocampal volumes (mean total volume: 4,961 mm³ vs. 5,578 mm³, p < 0.001), elevated WMH burden (>15 cm³ in 75.5% of cases), and higher prevalence of CSVD markers including lacunar infarcts (29.7% vs. 15.3%, p = 0.008) and microbleeds (26.5% vs. 11.0%, p = 0.002). Resting-state fMRI revealed significantly diminished functional connectivity between main DMN node pairs, especially between the PCC and mPFC (0.38 vs. 0.52, p < 0.001). Multivariate regression showed that hippocampal atrophy (OR = 3.42), WMH load (OR = 2.89) and diminished DMN connectivity (OR = 2.61) were powerful independent predictors of cognitive deterioration. In addition, BAG (+) was significantly associated with a higher risk of MCI, especially in those with type 2 diabetes (hazard ratio 1.13 per +1 year of age, p = 0.004). These results provide supportive evidence for use of multi-modal neuroimaging markers in the screening of early cognitive impairment among cardiometabolic patients. These biomarkers are potential targets for enhancing diagnosis and directing targeted preventive strategies.
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Umer Shabbir
Bahria University of Health Sciences/Midciti Hospital, Karachi
Imtiaz Manzoor
Chiniot General Hospital, Karachi
Iqra Anees Rajput
Dow University of Health Sciences, Karachi
Noman Ahmed Khan
Dow University of Health Sciences, Karachi
Ayesha Shahid
The Indus Hospital, Karachi
Sidra Anees
Bahria University of Health Sciences, Karachi
Tahir Ilyas
Tabba Kidney Institute, Karachi
Muhammad Muthar Anees
Liaquat College of Medicine and Dentistry, Karachi