Table 2.

Longitudinal studies of the relation of T2D with change in memory function

Author, Year	Sample Size (total), Age, and Follow-up	Study Groups	Source of Subjects	Covariates in Model Reported	Results
T2D defined by clinical testing and/or biomarkers
Beavers et al., 2017 (23)	879 participants Mean age (SD): 58.9 (6.79) Length of follow-up in years: 8	All 879 with T2D: 500 with A1C < 7%; 237 with A1C 7–8%; 142 with A1C >8%	Participants randomly selected among the Look AHEAD trial and Look AHEAD ancillary study, from across the US, all with T2D	Age, sex, race, education, smoking, alcohol, knee pain, metabolic equivalents, BMI, diabetes medications and statins, ancillary year visit, study arm and site	Among a group of participants with T2D, those with higher A1C levels had decreased physical function (p=0.03), but no decline in cognitive function (p=0.41 on global score) including on two measures of memory. Results did not differ when stratified by the mean baseline age.
Marden et al., 2018 (24)	8888 participants Mean age (SD): 67.4 (8.8) Mean follow-up in years: 5.2	1837 with T2D; 7051 without T2D	Population-based cohort of adults age 50+ from the Health and Retirement Study	Age, and several health and social confounders, including hypertension and stroke	People with T2D had faster rates of memory decline, compared to people without T2D (β=−0.04 per decade; 95% CI: −0.06,−0.01). Even among those without T2D, higher A1C level was related to faster memory decline (β=−0.05 per decade; 95% CI: −0.08,−0.03).
Cholerton et al. 2018 (22)	790 participants Mean Age (SD) with T2D: 53.0 (5.9); Mean Age (SD) with impaired fasting glucose:51.7 (5.5); Mean Age (SD) with normal glucose 51.3 (5.5) Mean follow-up in years: 21.1	185 with T2D; 344 with impaired fasting glucose; 261 with normal glucose	American Indian participants in the Strong Heart Study	Baseline age, sex, education, site, fluency of native language, baseline BMI, smoking, alcohol, APOE E4 allele presence	Participants with T2D were found to have a negative association when assessing verbal fluency (β = −3.583, p<0.001) and working memory/processing speed (β = −4.413, p=0.001) when compared to participants with normal fasting glucose.
Callisaya et al. 2019 (25)	705 participants Mean age (SD): 68.2 (7.0) Mean follow-up in years (SD): 4.6 (0.53)	348 with T2D; 357 without T2D	Participants >55yo from the National Diabetes Service Scheme registered in the Cognition and Diabetes in Older Tasmanians (CDOT) longitudinal study	Baseline stroke, hypertension, high cholesterol and obesity, and their interactions with time	Participants with T2D showed a significant decline over time in visual memory (β=0.11; 95% CI: 0.08, 0.14) and verbal memory (β=−0.06; 95% CI: −0.09, −0.02) compared to participants without T2D, but did not show a significant decline in working memory (β=−0.02; 95% CI: −0.05, 0.01).
T2D defined by self-report and/or medication
Bangen et al., 2015 (26)	1493 participants Mean age (SD) with T2D: 75.4 (5.8) Mean Age (SD) without T2D: 76.3 (6.7) Mean follow-up in years (SD): 6.05 (3.02)	378 with T2D; 1115 without T2D	Washington Heights-Inwood Columbia Aging Project (WHICAP) cohort	Age, sex, education, ethnicity, ApoE genotype	Compared to those without T2D, participants with T2D had lower baseline levels of cognitive function. However, participants with and without T2D showed similar rates of decline in memory (β = − 0.020, p = 0.603), language, speed/executive functioning, and visuospatial abilities.
Demakakos et al., 2017 (27)	10524 participants Mean Age (SD) without T2D with elevated depressive symptoms: 64.4 (9.9) Mean Age (SD) with T2D without elevated depressive symptoms: 68.4 (9.1) Mean Age (SD)without T2D with elevated depressive symptoms: 65.9 (10.8) Mean Age (SD) with T2D with elevated depressive symptoms: 67.4 (9.3) Length of follow-up in years: 10	8275 without T2D, with elevated depressive symptoms; 554 with T2D, without elevated depressive symptoms; 1526 without T2D, with elevated depressive symptoms; 169 with T2D, with elevated depressive symptoms	Community-dwellers aged ≥50 years in 2002–2003 from the English Longitudinal Study of Ageing	Age, sex, marital status, self-reported chronic conditions (heart disease, stroke, hypertension, chronic lung disease), education, occupational class, physical activity, smoking, alcohol consumption, BMI, adjustment for exposure*time interaction term	Participants with T2D have faster decline in memory, compared to participants without T2D, as determined by a word recall test. Memory declined faster among participants with both T2D and depressive symptoms, in mid-adult life, but not late-adult life (over age 65) (β= − 0.27, 95% CI, − 0.45 to − 0.08, per study wave).