👤 Laura Boero

Early diagnosis of Alzheimer's disease (AD) and related dementias remains challenging because no single biomarker sufficiently captures the complex and multifactorial nature of the underlying pathology. In recent years, multimodal artificial intelligence (AI) models capable of integrating heterogeneous data sources-such as neuroimaging, fluid biomarkers, genetics, and cognitive assessments-have emerged as a promising strategy to improve early detection and risk stratification. We performed a PRISMA-guided systematic review (PROSPERO: CRD420251049848) of studies published from 2010 to 2025. We included 27 peer-reviewed studies applying AI/ML to ≥2 biomarker modalities for diagnostic classification or prognostic prediction (e.g., MCI-to-AD conversion), with an explicit emphasis on multimodal designs that incorporated at least one minimally invasive and/or widely deployable modality (e.g., cognitive tests, blood-based biomarkers, APOE/genetics, retinal imaging, or routine clinical features). Risk of bias was assessed using QUADAS-2. Across the 27 included studies, multimodal AI models generally outperformed the best unimodal baselines, particularly when combining complementary biological information (e.g., imaging with molecular or clinical features). Diagnostic tasks more often achieved high discrimination (frequently AUCs in the ~0.85-0.95 range under internal validation), whereas prognostic prediction-especially MCI-to-AD conversion-remained more challenging (typically ~0.75-0.85 AUC in the best-performing models). However, evidence for generalizability was limited, as external validation was uncommon and QUADAS-2 frequently highlighted concerns in the Index Test domain related to overfitting risk and incomplete validation. Overall, multimodal AI provides a more comprehensive representation of AD/MCI-related pathology than unimodal approaches and can improve early diagnostic classification and, to a lesser extent, prognostic prediction. However, translation to clinical practice is still constrained by limited external validation and heterogeneous reporting, which hamper generalizability and clinical trust. Future work should prioritize prospective multi-center studies, robust external validation, and transparent reporting (including interpretability analyses) to support real-world deployment. Show less

Abdominal obesity is an important cardiovascular disease risk factor. Plasma fatty acids display a complex network of both pro and antiatherogenic effects. High density lipoproteins (HDL) carry out the antiatherogenic pathway called reverse cholesterol transport (RCT), which involves cellular cholesterol efflux (CCE), and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. Our aim was to characterize RCT and its relation to fatty acids present in plasma in pediatric abdominal obesity. Seventeen children and adolescents with abdominal obesity and 17 healthy controls were studied. Anthropometric parameters were registered. Glucose, insulin, lipid levels, CCE employing THP-1 cells, LCAT and CETP activities, plus fatty acids in apo B-depleted plasma were measured. The obese group showed a more atherogenic lipid profile, plus lower CCE (Mean±Standard Deviation) (6 ± 2 vs. 7 ± 2%; P < 0.05) and LCAT activity (11 ± 3 vs. 15 ±5 umol/dL.h; P < 0.05). With respect to fatty acids, the obese group showed higher myristic (1.1 ± 0.3 vs. 0.7 ± 0.3; P < 0.01) and palmitic acids (21.5 ± 2.8 vs. 19.6 ± 1.9; P < 0.05) in addition to lower linoleic acid (26.4 ± 3.3 vs. 29.9 ± 2.6; P < 0.01). Arachidonic acid correlated with CCE (r = 0.37; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05), palmitioleic acid with CCE (r = -0.35; P < 0.05), linoleic acid with CCE (r = 0.37; P < 0.05), lauric acid with LCAT (r = 0.49; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05) ecoisatrienoic acid with CCE (r = 0.40; P < 0.05) and lignoseric acid with LCAT (r = -0.5; P < 0.01). Children and adolescents with abdominal obesity presented impaired RCT, which was associated with modifications in proinflammatory fatty acids, such as palmitoleic and myristic, thus contributing to increased cardiovascular disease risk. Show less

Overweight/obesity (OW/OB) is associated with modifications in lipoprotein (Lp)-associated enzymes and proteins, such as cholesteryl ester transfer protein (CETP), Lp-associated phospholipase A To analyze the presence of alterations in Lp-associated enzymes and proteins in children and adolescents with UW and OW/OB and their relation to novel cardiometabolic indexes. Thirty male children and adolescents with UW, 66 with normal weight (NW) and 30 with OW/OB were included. Anthropometric parameters, glucose, Lp profile and the activities of CETP, LpPLA Both UW and OW/OB showed impaired antioxidant PON1 activity. Moreover, TyG, VAI and HLAP were all capable of predicting alterations in crucial modulators of Lp metabolism and vascular inflammation in children and adolescents with varying degrees of alterations in body weight. Show less

To explore the association between Triglyceride/High-density lipoprotein cholesterol (TG/HDL-C) index and these enzymes and proteins in a pediatric population. Children and adolescents (7-14 y old) were recruited (n = 150) and anthropometric data were registered. Glucose, TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C plus cholesteryl ester transfer protein (CETP), lipoprotein-associated phospholipase A Twenty-five individuals presented TG/HDL-C ratio ≥ 3.0. These individuals exhibited higher TG [164 (126-186) vs. 65 (48-72) mg/dL; p < 0.01] CETP [250 (232-263) vs. 223 (193-237)% mL/min; p < 0.01] and Lp-PLA Children and adolescents with TG/HDL-C ≥ 3.0 presented a more atherogenic lipid profile and higher CETP and Lp-PLA Show less

Morbid obesity represents the most severe form of obesity and surgical intervention would be its only successful treatment. Bariatric surgery could generate modifications in carbohydrate metabolism and in lipid profile plus lipoprotein-associated proteins and enzymes, such as lipoprotein-associated phoslipase A Thirty-seven patients with morbid obesity were recruited. Evaluations were performed before (T0) and 1 (T1) and 6 (T2) months after surgery. Glucose, insulin, high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apolipoproteins (apo) A-I, and B plus Interleukin 1β and 6 levels in addition to CETP, Lp-PLA2, and PON 1 activities were determined. Body mass index decreased at T1 and T2 (p < 0.01). An improvement in all markers of insulin resistance (p < 0.05) was observed at T1. hsCRP levels diminished at T2 (p < 0.05). Triglyceride levels decreased at T1 and T2 (p < 0.05). HDL-C and apo A-I showed a decrease at T1 which was completely reversed at T2 (p < 0.05). Lp-PLA These results would be indicative of a favorable effect of bariatric surgery on markers of carbohydrate metabolism and cardiovascular disease lipid risk factors. Show less