Table 1.

Association of T2D^* with level of memory function

Author, Year	Sample Size (total) and Age	Study Groups	Source of Subjects	Covariates in Model Reported	Results
Spauwen et al., 2015(14)	713 participants Mean age (SD), T2D group : 63.7 (7.0); non-T2D: 58.3 (8.5)	201 with T2D; 512 without T2D	Population-based cohort, Maastricht study	Age, sex, education, smoking, alcohol, waist circumference, cholesterol ratio, triglycerides, antihypertensive medications, lipid-modifying medications, eGFR, cardiovascular disease, depression	In participants with T2D, an inverted U-shaped relationship was found between diastolic blood pressure and memory and information processing speed (immediate word recall: β =−0.0180, p < 0.05; delayed word recall: β =−0.0076, p < 0.01). No relationship of blood pressure and cognition was observed in people without T2D.
Spauwen, et al. 2015 (18)	764 participants, 215 with and 549 without T2D Mean Age (SD) with low skin autofluorescence: 54.9 (8.7) Mean Age (SD) with middle skin autofluorescence: 60.2 (7.3) Mean Age (SD) with high skin autofluorescence: 63.8 (6.9)	254 with low skin autofluorescence; 255 with mild skin autofluorescence; 255 with high skin autofluorescence	Population-based cohort, Maastricht Study	Age, sex, diabetes, educational level, smoking, alcohol, waist circumference, total cholesterol/HDL ratio, triglycerides, lipid-lowering medication use	Skin autofluorescence (SAF) was used as a measurement of advanced glycation end-products (AGEs). In the total group, higher SAF was associated with worse delayed word recall (β=‒ 0.44, p=0.04)
Gao et al. 2015 (19)	492 participants Mean age (SD) T2D with mild cognitive impairment (MCI): 73.92 (2.17) Mean age (SD) T2D with normal cognition: 74.15 (3.92)	246 with T2D and MCI; 246 with T2D and normal cognition	Community-dwelling residents ≥65yo	Sex, age, educational level	Participants with T2DM-MCI did worse on word learning delayed recall, a test of memory, compared to those with T2DM-normal cognition (p=0.015).
Greenbaum et al., 2016 (17)	848 participants Mean Age (SD): 71.98 (4.72)	All 848 had T2D, and BIN1 testing was done	Israel Diabetes and Cognitive Decline sample of patients with T2D	Age, sex, education, disease duration, ancestry	Among participants with T2D, differences in a SNP near the BIN1 gene suggested associations with episodic memory. The TT genotype was associated with lower scores than the CT or CC genotype (F(1,834)=7.664, p=0.00576).
Marseglia et al., 2016 (16)	2305 participants Mean Age (SD) with T2D: 73.9 (9) Mean Age (SD) with pre-T2D: 74 (10) Mean Age (SD) without T2D: 71 (10)	196 with T2D: 144 with uncontrolled T2D (A1C > 6.4%) and 52 with controlled T2D (A1C 5.7–6.4%); 571 with pre-T2D (A1C 5.7–6.4% in T2D-free participants); 1538 without T2D	Population-based cohort, Swedish national study on Aging and Care-Kungsholmen study	Age, sex, education	T2D was not associated with episodic memory (p = 0.418), semantic memory (p =0.379), or a test of working memory (p = 0.119).
Geijsalaers et al. 2017 (21)	806 participants Mean age (SD): 62 (8)	All 806 participants with T2D	Population-based cohort, Maastricht Study	Age, sex, education, A1c, fasting glucose, waist circumference, total/HDL cholesterol ratio, use of lipid-modifying medications, systolic and diastolic blood pressure, use of antihypertensives, depression	Among participants with T2D, demographic factors accounted for 18% of variance in performance on memory function tests. In addition to these factors, fasting insulin and C-peptide did not significantly contribute to the variance in memory function test scores.
Geijsalaers et al. 2017 (20)	2531 participants Mean age (SD) normal glucose metabolism (NGM): 58 (8) Mean age (SD) prediabetes: 62 (7) Mean age (SD) T2D: 63 (8)	1479 with NGM; 386 with prediabetes; 666 with T2D	Population-based cohort, Maastricht Study	Age, sex, education	Participants with T2D did worse on measures of memory than those with NGM (p< 0.05), but participants with prediabetes did not do worse compared to those with T2D (p = 0.035).
van Gemert, et al., 2018 (15)	353 participants Mean Age (SD) with recent diagnosis of T2D: 59 (9) Mean Age (SD) with T2D >12months: 59 (10)	201 with recently diagnosed diabetes:119 with T2D; 110 with known diabetes for five years: 65 with T2D; 42 without diabetes	Population-based cohort, German Diabetes Study	M value, hsCRP, A1C, crystallized intelligence, BMI, age, sex	In participants with a recent diagnosis of T2D (within the last 12 months), verbal memory scores were lower compared to participants without T2D (β= −0.49 (−0.93; – 0.05) p= 0.029).

^*T2D defined by clinical testing and/or biomarkers in all studies listed in table