Table 1. Summary of the included studies.
| Reference | Year | Design | Sample size | Objective | Conclusions | Risk of bias as per QUADAS-2 |
|---|---|---|---|---|---|---|
| Su et al. 12 | 2016 | Case-control | 222 | “Longitudinal study for an average of 35 months to assess cognitive decline over time” | “The results suggested that the restoration of insulin activity represents a promising therapeutic target for improve cognitive decline in AD”. | Good-quality |
| Niyasti et al. 13 | 2022 | Case-control | 300 | “Polymerase chain reaction was performed to amplify a DNA segment of 263 base-pair length containing the single nucleotide polymorphism” | “Association of Insulin Receptor Substrate-1 Gene Polymorphism (rs1801278) present at the BIR is significantly associated with the risk of developing AD” | Good-quality |
| van der Velpen et al. 14 | 2019 | Case-control | 74 | “Paired plasma and cerebrospinal fluid samples” | “The study showed the translational potential of the pathway quantitative to assess central nervous system metabolic defects which are part of the AD pathophysiology”. | Low-moderate |
| Andalib et al. 15 | 2019 | Case-control | 243 | “To test the hypothesis of association of late onset Alzheimer’s disease (AD) with DM2 in an Iranian population” | “The evidence from the present study suggested that DM2 was associated with AD in an Iranian population” | Good-quality |
| Mullins et al. 16 | 2018 | Case-control | 54 | “Use Magnetic Resonance Spectroscopy to assess AD-related differences in the posterior cingulate/precuneal ratio of glucose, lactate, and other metabolites” | The study showed substantial elevations in glucose, lactate, and ascorbate levels within the posterior cingulate/precuneus of AD participants | Good-quality |
| Xu et al. 17 | 2016 | Case-control | 18 | “To elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage” | “Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD” | Good-quality |
| Tortelli et al. 18 | 2017 | Cohort | 797 | “To evaluate midlife metabolic profile and the risk of late-life cognitive decline” | “The control blood glucose levels, regardless of a diagnosis of diabetes mellitus, as early as midlife prevents late-life dementia” | Good-quality |
| Abner et al. 19 | 2016 | Cohort | 2,365 | “SMART database that comprises a standardized set of data elements contributed by 11 longitudinal studies of aging and cognition” | “The study concluded that diabetes increases the risk of cerebrovascular but not AD” | Low-moderate |
| Chung et al. 20 | 2015 | Case-control | 900 | “Investigate whether genome-wide significant loci of type 2 diabetes mellitus are associated with the risk of AD” | “The results suggest that genome-wide significant loci of type diabetes (insulin resistance) play no major role in the risk and cognitive impairment of AD” | Low-moderate |
| Schrijvers et al. 21 | 2010 | Cohort | 3,139 | “Investigate whether fasting glucose and insulin levels and IR are associated with the risk of AD and whether this risk is constant over time” | “The study suggests that insulin metabolism influences the clinical manifestation of AD only within 3 years” | Good-quality |
| Willette et al. 22 | 2015 | Cross-sectional | 186 | “Assess whether the IR is associated with amyloid binding in three AD-sensitive brain areas” | “The study demonstrated that IR may contribute to amyloid deposition in brain regions affected by AD” | Good-quality |
| Morris et al. 23 | 2014 | Cross-sectional | 42 | “To compare IR in aging and aging-related neurodegenerative diseases, and to determine the relationship between IR and gray matter volume in each cohort using an unbiased, voxel-based approach” | “The study supports a potential relationship between IR and brain structure in both normal aging and diagnosed neurodegenerative disease” | Good-quality |
| Kapogiannis et al. 24 | 2015 | Cross-sectional | 26 | “To assess brain IR in AD by level of serine-type 1 insulin receptor substrate (IRS-1) and its state of phosphorylation in neural-derived plasma exosomes” | “Insulin resistance reflected in R values from IRS-1 is higher for patients with AD, and accurately predicts development of AD up to 10 year prior to clinical onset” | Good-quality |
| Willette et al. 25 | 2015 | Cross-sectional | 150 | “To determine if IR predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD, and to examine if IR predicts variation in regional glucose metabolism is associated with worse cognitive performance” | “The results show that IR is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance” | Good-quality |
| Johansson et al. 26 | 2013 | Cross-sectional | 80 | “Assess whether the serum but not cerebrospinal fluid levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 are increased in AD” | “Patients with AD as well as other dementias had high levels of IGF-I in serum but not in CSF. In AD patients, the IGF-I system was associated with biomarkers of AD disease status” | Good-quality |
| Faqih et al. 27 | 2021 | Cohort | 356 | “Study the association between AD and IR and the relation between AD and diabetic patients treated with insulin” | “The results suggest that AD is associated with IR” | Good-quality |
| Hong et al. 28 | 2021 | Cohort | 5,586,048 | “Study the potential relationships between the triglyceride glucose index and dementia” | “Triglyceride glucose index was associated with an increased risk of dementia, including AD” | Good-quality |
Abbreviations: QUADAS, Quality Assessment of Diagnostic Accuracy Studies; AD, Alzheimer’s disease; IR, insulin resistance; DM2, type 2 diabetes mellitus; IGF, insulin-like growth factor; IRS, insulin receptor substrate.