The DOI matches its Crossref record; 89 of the 90 references it cites were found in a registry or an index; none of the 86 sources its claims cite is checked for support yet.
Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies
Abstract
Aims/hypothesis We systematically reviewed and summarised prospective data relating diabetes status to changes in cognitive function over time.Methods Published reports of longitudinal studies that described assessment of cognitive function in people with diabetes were sought. Studies were included if they assessed cognitive function in participants with diabetes at the beginning and at follow-up. Studies were excluded if they had (1) a follow-up period of less than 1 year, (2) a rate of loss to follow-up in excess of 30%, or (3) described selected subgroups. Change in cognitive function was recorded as either the mean change in score and/or the proportion of individuals developing various degrees of change in cognitive function. A pooled estimate was calculated for the latter.Results Of 1,165 abstracts and titles initially identified, 25 articles met the inclusion and exclusion criteria. Individuals with diabetes had a 1.2- to 1.5-fold greater change over time in measures of cognitive function than those without diabetes. When assessed by the Mini-Mental State Exam and the Digit Symbol Span tests, a diagnosis of diabetes increased the odds of cognitive decline 1.2-fold (95% CI 1.05-1.4) and 1.7-fold (95% CI 1.3-2.3), respectively . The odds of future dementia increased 1.6-fold (95% CI 1.4-1.8).Conclusions/interpretation Compared to people without diabetes, people with diabetes have a greater rate of decline in cognitive function and a greater risk of cognitive decline. Cognitive dysfunction should therefore be added to the list of chronic complications of diabetes.
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TL;DR
This systematic overview of 25 prospective observational studies found that people with diabetes have greater cognitive decline and a higher risk of dementia than people without diabetes. The authors conclude that cognitive dysfunction should be added to the list of chronic complications of diabetes.
Key findings
- Among 25 included articles covering more than 8,656 people with diabetes and follow-up periods of 2 to 18 years, diabetes was associated with a 1.2- to 1.5-fold greater change over time in measures of cognitive function.
- Pooled estimates showed increased odds of cognitive decline on the MMSE/3MS (OR 1.2, 95% CI 1.05–1.4) and DSS (OR 1.7, 95% CI 1.3–2.3), and a 1.6-fold higher risk of future all-cause dementia (95% CI 1.4–1.8).
- For dementia subtypes, risks ranged from 1.2 to 2.3 for Alzheimer’s disease and from 2.2 to 3.4 for vascular dementia.
- In continuous DSS analyses, three studies reported a decline of 1.3 to 1.4% per year in people with diabetes; overall this decline was up to 1.5 times greater than in people without diabetes.
Methods
- Systematic review of longitudinal/prospective observational studies; Medline, EMBASE, and PsycINFO were searched, along with expert contact and bibliography review. Of 1,165 abstracts/titles, 50 were fully reviewed and 25 met inclusion/exclusion criteria.
- Inclusion required baseline and follow-up cognitive assessment, diabetes or glucose tolerance status, and English-language reporting; exclusions were follow-up under 1 year, loss to follow-up over 30%, or selected subgroups.
- Data were abstracted on age, diabetes definition, participant numbers, follow-up length, cognitive tools, and outcomes; pooled inverse variance-weighted log risk ratios with 95% CIs were calculated, with heterogeneity assessed by the Q statistic using Review Manager 4.2.
Limitations
- The paper states possible publication bias, though it argues this is unlikely because many included studies were prospective cohorts examining many risk factors; it also states that MMSE/3MS may underestimate diabetes effects because it poorly detects attention and processing speed.
- The paper states that included studies differed in definitions of clinically meaningful decline, diabetes identification, age groups, cognitive tools, statistical adjustment, baseline cognitive impairment, and follow-up completeness (73–92%), and that there is no evidence to date that diabetes management affects the rate or nature of cognitive dysfunction.
- Evident from the text: only three studies explicitly reported that data were collected without examiner awareness of diabetes status, and some pooled estimates relied on few studies, such as the DSS estimate based on two studies.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Individuals with diabetes had a 1.2- to 1.5-fold greater change over time in measures of cognitive function than those without diabetes.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The odds of future dementia increased 1.6-fold (95% CI 1.4 -1.8).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The definitions of dementia used in the included studies are sufficiently comparable to be combined in the review.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When assessed by the Mini-Mental State Exam and the Digit Symbol Span tests, a diagnosis of diabetes increased the odds of cognitive decline 1.2-fold (95% CI 1.05 -1.4) and 1.7-fold (95% CI 1.3 -2.3), respectively.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The 25 remaining articles [46 -70] comprised data from more than 8,656 people with diabetes, with follow-up periods ranging from 2 to 18 years.”
What the sources say
- Not checked yetcites [46 -70]
Strength:plain· not yet calibratedn = 8,656Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When assessed by the Mini-Mental State Exam and the Digit Symbol Span tests, a diagnosis of diabetes increased the odds of cognitive decline 1.2-fold (95% CI 1.05 -1.4) and 1.7-fold (95% CI 1.3 -2.3), respectively.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“However, in contrast to the acute negative effect of hypoglycaemia on cognition, there is little evidence to support chronic cognitive impairment secondary to hypoglycaemia.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared to people without diabetes, people with diabetes were 1.2 times more likely to experience cognitive decline as measured by the MMSE/3MS (95% CI 1.0 -1.4) and 1.7 times more likely to experience cognitive decline as measured by the DSS (95% CI 1.3 -2.3).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The cognitive assessment instruments used across the included studies measure cognitive decline in a comparable way.
None of the sources cited for this claim have been checked yet.
In the paper
“Table 2 lists the six studies that reported time-related changes as a continuous variable using either the MMSE or 3MS score in individuals with and without a history of diabetes [49, 51, 52, 54, 65, 69].”
What the sources say
- Not checked yetcites [49] Wu JH, Haan MN, Liang J, Ghosh D, Gonzalez HM, Herman WH (2003) Impact of antidiabetic medications on physical and cognitive functioning of older Mexican Americans with diabetes mellitus: a population-based cohort study. Ann Epidemiol 13:369–376 source
- Not checked yetcites [51] Fontbonne A, Berr C, Ducimetiere P, Alperovitch A (2001) Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care 24:366–370 source
- Not checked yetcites [52] Haan MN, Shemanski L, Jagust WJ, Manolio TA, Kuller L (1999) The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA 282:40–46 source
- Not checked yetcites [54] Gregg EW, Yaffe K, Cauley JA et al (2000) Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group. Arch Intern Med 160:174–180 source
- Not checked yetcites [65] Hassing LB, Hofer SM, Nilsson SE et al (2004) Comorbid type 2 diabetes mellitus and hypertension exacerbates cognitive decline: evidence from a longitudinal study. Age Ageing 33:355–361 source
- Not checked yetcites [69] Kanaya AM, Barrett-Connor E, Gildengorin G, Yaffe K (2004) Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med 164:1327–1333 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In these studies, diabetes status predicted an odds ratio for cognitive decline that ranged from 0.7 to 4.4.”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The cognitive assessment instruments used across the included studies measure cognitive decline in a comparable way.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three studies reported a decline ranging from 1.3 to 1.4% per year in people with diabetes.”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Probably not a substantial claim. 12
- It may state two separate claims as one. 17
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of 1,165 abstracts and titles initially identified, 25 articles met the inclusion and exclusion criteria.”
- Also stated in: § Search · p. 3 · plain
“The 25 remaining articles [46 -70] comprised data from more than 8,656 people with diabetes, with follow-up periods ranging from 2 to 18 years.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Also stated in: § Search · p. 3 · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of these citations, 50 met the inclusion criteria and were fully reviewed and analysed.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 25 remaining articles [46 -70] comprised data from more than 8,656 people with diabetes, with follow-up periods ranging from 2 to 18 years.”
Strength:plain· not yet calibratedn = 8,656Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Table 3, and Figs. 1 and 2 list and display results from the six studies that used the MMSE or 3MS [47 -51, 54, 62, 69] and the two studies that used the DSS [51, 54] to classify participants into those who did and did not experience cognitive decline.”
What the sources say
- Not checked yetcites [47] Nguyen HT, Black SA, Ray LA, Espino DV, Markides KS (2002) Predictors of decline in MMSE scores among older Mexican Americans. J Gerontol A Biol Sci Med Sci 57:M181–M185 source
- Not checked yetcites [48] Wu JH, Haan MN, Liang J, Ghosh D, Gonzalez HM, Herman WH (2003) Impact of diabetes on cognitive function among older Latinos: a population-based cohort study. J Clin Epidemiol 56:686–693 source
- Not checked yetcites [49] Wu JH, Haan MN, Liang J, Ghosh D, Gonzalez HM, Herman WH (2003) Impact of antidiabetic medications on physical and cognitive functioning of older Mexican Americans with diabetes mellitus: a population-based cohort study. Ann Epidemiol 13:369–376 source
- Not checked yetcites [50] Haan MN, Mungas DM, Gonzalez HM, Ortiz TA, Acharya A, Jagust WJ (2003) Prevalence of dementia in older Ltinos: the influence of type 2 diabetes mellitus, stroke and genetic factors. J Am Geriat Soc 51:169–177 source
- Not checked yetcites [51] Fontbonne A, Berr C, Ducimetiere P, Alperovitch A (2001) Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care 24:366–370 source
- Not checked yetcites [54] Gregg EW, Yaffe K, Cauley JA et al (2000) Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group. Arch Intern Med 160:174–180 source
- Not checked yetcites [62] Stewart R, Prince M, Mann A (2003) Age, vascular risk, and cognitive decline in an older, British, African-Caribbean population. J Am Geriat Soc 51:1547–1553 source
- Not checked yetcites [69] Kanaya AM, Barrett-Connor E, Gildengorin G, Yaffe K (2004) Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med 164:1327–1333 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“However, one study reported an improvement in score of 1.2% in people with diabetes; nevertheless this improvement was approximately half of the improvement experienced by the non-diabetic participants [51].”
What the sources say
- Not checked yetcites [51] Fontbonne A, Berr C, Ducimetiere P, Alperovitch A (2001) Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care 24:366–370 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Four studies used the DSS as a continuous variable (Table 2) to assess cognitive function and three reported an adverse effect of diabetes on cognitive function over time.”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Five of these studies reported that participants with diabetes had a higher risk of developing cognitive decline than those without diabetes; in three of these the lower limit of the 95% confidence interval exceeded 1 (i.e. it was statistically significant).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The definitions of dementia used in the included studies are sufficiently comparable to be combined in the review.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Seventeen studies divided the participants into two groups based on whether or not participants did or did not experience cognitive decline during follow-up.”
Strength:plain· not yet calibratedn = 17Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Eight studies reported a variety of other cognitive tests, most of them reporting greater or equal cognitive change for the diabetic participants (Table 1) [46, 49, 51, 58, 63, 66, 69, 70]. Some, but not all of the tests detected a significant difference between the groups with and without diabetes.”
What the sources say
- Not checked yetcites [46] Logroscino G, Kang JH, Grodstein F (2004) Prospective study of type 2 diabetes and cognitive decline in women aged 70–81 years. BMJ 328:548 source
- Not checked yetcites [49] Wu JH, Haan MN, Liang J, Ghosh D, Gonzalez HM, Herman WH (2003) Impact of antidiabetic medications on physical and cognitive functioning of older Mexican Americans with diabetes mellitus: a population-based cohort study. Ann Epidemiol 13:369–376 source
- Not checked yetcites [51] Fontbonne A, Berr C, Ducimetiere P, Alperovitch A (2001) Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care 24:366–370 source
- Not checked yetcites [58] Leibson CL, Rocca WA, Hanson VA et al (1997) Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol 145:301–308 source
- Not checked yetcites [63] Robertson-Tchabo EA, Arenberg D, Tobin JD, Plotz JB (1986) A longitudinal study of cognitive performance in noninsulin dependent (type II) diabetic men. Exp Gerontol 21:459–467 source
- Not checked yetcites [66] Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA (2004) Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 61:661–666 source
- Not checked yetcites [69] Kanaya AM, Barrett-Connor E, Gildengorin G, Yaffe K (2004) Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med 164:1327–1333 source
- Not checked yetcites [70] Yaffe K, Blackwell T, Kanaya AM, Davidowitz BA, Barrett-Connor E, Krueger K (2004) Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology 63:658–663 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In these studies, individuals with diabetes had a greater absolute annual decline in score than those without diabetes; however, the differences only achieved statistical significance in one study [70].”
What the sources say
- Not checked yetcites [70] Yaffe K, Blackwell T, Kanaya AM, Davidowitz BA, Barrett-Connor E, Krueger K (2004) Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology 63:658–663 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The selected studies were analysed according to previously published methodological criteria [12] to determine if they reported: (1) a predetermined method for selection of the participants; (2) the definition of diabetes mellitus; (3) the definition of the outcome; (4) use of the same cognitive assessment instrument in the two groups; (5) that data were collected unaware of the diabetes status (b”
What the sources say
- Not checked yetcites [12] Horwitz RI, Feinstein AR (1979) Methodologic standards and contradictory results in case-control research. Am J Med 66:556–564 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Only three studies explicitly reported that data were collected without the examiner being aware of the diabetes status of the participant [46, 51, 62].”
What the sources say
- Not checked yetcites [46] Logroscino G, Kang JH, Grodstein F (2004) Prospective study of type 2 diabetes and cognitive decline in women aged 70–81 years. BMJ 328:548 source
- Not checked yetcites [51] Fontbonne A, Berr C, Ducimetiere P, Alperovitch A (2001) Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care 24:366–370 source
- Not checked yetcites [62] Stewart R, Prince M, Mann A (2003) Age, vascular risk, and cognitive decline in an older, British, African-Caribbean population. J Am Geriat Soc 51:1547–1553 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Heterogeneity was assessed using the Q statistic [20].”
What the sources say
- Not checked yetcites [20] Laird NM, Mosteller F (1990) Some statistical methods for combining experimental results. Int J Technol Assess Health Care 6:5–30 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The validity of the MMSE as a screening tool for detecting dementia has been extensively studied [17]; its ability to detect changes in cognitive function for non-demented individuals has been documented mainly in the elderly [18].”
What the sources say
- Not checked yetcites [17] Tombaugh TN, McIntyre NJ (1992) The mini-mental state examination: a comprehensive review. J Am Geriatr Soc 40:922–935 source
- Not checked yetcites [18] Brayne C, Spiegelhalter DJ, Dufouil C et al (1999) Estimating the true extent of cognitive decline in the old. J Am Geriatr Soc 47:1283–1288 source
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ple with diabetes have a greater rate of decline in cognitive function and a greater risk of cognitive decline.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The definitions of dementia used in the included studies are sufficiently comparable to be combined in the review.
- Rests on an assumption: The cognitive assessment instruments used across the included studies measure cognitive decline in a comparable way.
- Rests on an assumption: The included studies' participants with diabetes are representative of people with diabetes generally.
In the paper
“Compared to non-diabetic individuals, diabetes increased the risk of vascular dementia and Alzheimer ' s dementia 1.3 and 4.4-fold, respectively.”
What the sources say
- Not checked yetcites [72] Yamada M, Kasagi F, Sasaki H, Masunari N, Mimori Y, Suzuki G (2003) Association between dementia and midlife risk factors: the Radiation Effects Research Foundation Adult Health Study. J Am Geriat Soc 51:410–414 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Experimental studies in animal models and in humans without diabetes have shown that poor glucose regulation after a glucose challenge test was associated with poorer performance on a variety of cognitive tests, the effect being more pronounced in the older age group [81].”
What the sources say
- Not checked yetcites [81] Messier C (2004) Glucose improvement of memory: a review. Eur J Pharmacol 490:33–57 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Another factor suggesting that the reports underestimated the effect of diabetes on cognitive decline is the fact that most of the studies did not include information on people who died or who were lost to follow-up, when follow-up success itself could well be linked to good cognitive function.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These findings are supported by previous reviews of the available longitudinal studies [3, 4, 6].”
What the sources say
- Not checked yetcites [3] Allen KV, Frier BM, Strachan MW (2004) The relationship between type 2 diabetes and cognitive dysfunction: longitudinal studies and their methodological limitations. Eur J Pharmacol 490:169–175 source
- Not checked yetcites [4] Areosa Sastre A, Grimley Evans J (2005) Effect of the treatment of Type II diabetes mellitus on the development of cognitive impairment and dementia. The Cochrane Library, Issue 2, http://www.cochrane.org/cochrane/revabstr/AB003804.htm
- Not checked yetcites [6] Stewart R, Liolitsa D (1999) Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med 16:93–112 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Indeed, a recent review of the effect of therapy concluded that no studies were appropriate for inclusion in meta analysis [4].”
What the sources say
- Not checked yetcites [4] Areosa Sastre A, Grimley Evans J (2005) Effect of the treatment of Type II diabetes mellitus on the development of cognitive impairment and dementia. The Cochrane Library, Issue 2, http://www.cochrane.org/cochrane/revabstr/AB003804.htm
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“As these domains may be selectively impaired in people with diabetes the MMSE/3MS will underestimate the impact of diabetes on cognitive function [10].”
What the sources say
- Not checked yetcites [10] Strachan MW, Deary IJ, Ewing FM, Frier BM (1997) Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies. Diabetes Care 20:438–445 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study is also limited by the differences in the studies included with respect to: (1) the definition of a clinically meaningful decline in cognitive function; (2) identification of people with and without diabetes; (3) age groups that were studied; (4) cognitive assessment tools employed; (5) degree of statistical adjustment for confounders; (6) degree of cognitive impairment permitted in stud”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In one study, this finding was only noted in young participants, while findings in older participants were consistent with the results from the other studies [62].”
What the sources say
- Not checked yetcites [62] Stewart R, Prince M, Mann A (2003) Age, vascular risk, and cognitive decline in an older, British, African-Caribbean population. J Am Geriat Soc 51:1547–1553 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, many of the studies analysed by us were prospective cohort studies, which examined many risk factors for cognitive decline, and not just diabetes. This makes it unlikely that a lack of an association with diabetes would lead to non-publication.”
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In the other study, this finding was only noted for women, and only in certain cognitive tests. The large confidence interval and wide variability of scores between tests reported in this study suggest that a larger sample size could possibly have altered the results [69].”
What the sources say
- Not checked yetcites [69] Kanaya AM, Barrett-Connor E, Gildengorin G, Yaffe K (2004) Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med 164:1327–1333 source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
The definitions of dementia used in the included studies are sufficiently comparable to be combined in the review.
“The definition of dementia used in each study was accepted for this review.”
The paper relies on this without support.
The cognitive assessment instruments used across the included studies measure cognitive decline in a comparable way.
“Cognitive function was measured using a variety of simple cognitive tests [9, 13, 14].”
The paper relies on this without support.
The included studies' participants with diabetes are representative of people with diabetes generally.
“The 25 remaining articles [46 -70] comprised data from more than 8,656 people with diabetes, with follow-up periods ranging from 2 to 18 years.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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In the citing paper
“Older adults with diabetes are at higher risk of cognitive decline and institutionalization (12,13).”
From 13. Older Adults: Standards of Care in Diabetes—2024 (2024) · cites this paper as [12]
Experimental — accuracy not yet measuredIn the citing paper
“Type 2 diabetes (T2D) has been demonstrated to be related to accelerated cognitive decline (3) and increased risk of dementia (4)”
From Type 2 Diabetes and Antidiabetic Medications in Relation to Dementia Diagnosis (2014) · cites this paper as [3]
In the citing paper
“Cross-sectional studies have shown an association between hyperglycemia and cognitive dysfunction62.”
From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [62]
In the citing paper
“Evidence for impairments in peripheral insulin signalling in patients with AD was presented more than 25 years ago, 138 and the incidence of AD is known to be increased in patients with metabolic impairments such as diabetes 139,140 ; fittingly, some cognitive domains have been consistently found to be affected in type 2 diabetes (eg, memory, psychomotor speed, executive function).113”
From Intranasal insulin (2021) · cites this paper as [139]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Fig. 3 non-diabetes-group total does not sum to its available counts
MinorThe four numerical non-diabetes-group counts displayed in Fig. 3 sum to 11,497, not the reported total of 10,044; the remaining study's count is marked NA.
Reported 10044 · recomputed 11497
“| Total (95% CI) | 2723 | 10044 | 1.6 (1.4, 1.8) |”
Gregg comparison-group count differs between Table 3 and Fig. 1
MinorFig. 1 lists 584 participants without diabetes for Gregg et al., whereas Table 3 lists 5,844 for the same study. The Fig. 1 total is consistent with 5,844, not 584.
“| Gregg et al [54] | 402 | 584 | 1.0 (0.8, 1.4) |”
“| MMSE/3MS | [54] | 65 - 99 (F) | History | 6 | 402 | 5844 | ≥ 11.5% a | 1.0 (0.8 - 1.4) e |”
Fig. 3 diabetes-group total does not sum to its study counts
MinorThe five diabetes-group counts displayed in Fig. 3 sum to 3,585, not the reported total of 2,723.
Reported 2723 · recomputed 3585
“| Total (95% CI) | 2723 | 10044 | 1.6 (1.4, 1.8) |”
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“It was not only shown that diabetes increases the risk of dementia [6,7] but also accelerates cognitive decline in older persons without dementia [8].”
BackgroundMa, L., Shao, Z., Wang, R., Zhao, Z., Dong, W., Zhang, J., Zhang, X., Sheng, S., Ji, Z., & Zhang, J. (2015) · The American Journal of the Medical Sciences · doi:10.1097/maj.0000000000000499 · Cited by 25
“5- to 2-fold increased risk of developing cognitive impairment.(1,2) Some scholars believe that the disorder in brain function is caused by insulin signal transduction impairment or “diabetic encephalopathy,”(3) which has been recognized as one of the complications of diabetes.”
BackgroundRostampour, N. (2017) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2017/26623.10541 · Cited by 25
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Javanshiri, K., Haglund, M., & Englund, E. M. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190485 · Cited by 25
“Diabetes is accepted as a risk factor for cognitive impairment and cognitive decline [44].”
BackgroundLifestyle intervention to prevent Alzheimer’s disease
Ko, Y., & Chye, S. M. (2020) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0072 · Cited by 29
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“Such findings reiterate that cognitive impairment is not a complication of T2D that is limited only to older adult patients and that both T2D [4] and metabolic syndrome [27] are known to accelerate cognitive decline.”
Backgroundvan Schalkwyk, G. I., Botha, H., & Seedat, S. (2012) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988712447895 · Cited by 25
“The utility of the MMSE in detecting cognitive change in general medical populations has also been questioned.(10) Despite this, its use in clinical practice remains widespread.”
MethodAtif, M., Saleem, Q., & Scahill, S. (2017) · International Journal of Diabetes in Developing Countries · doi:10.1007/s13410-017-0600-3 · Cited by 25
Galea, E., Feinstein, D. L., & Lacombe, P. M. (2006) · Diabetologia · doi:10.1007/s00125-006-0326-0 · Cited by 25
“This issue is of current interest since (1) several million diabetic patients take pioglitazone, (2) these patients suffer from a greater rate of cognitive decline [27, 28], and (3) pioglitazone is being tested for the treatment of neurological diseases (for information about clinical trials in progress see [6]).”
Wennberg, A. M. V., Gottesman, R. F., Kaufmann, C. N., Albert, M., Chen-Edinboro, L. P., Rebok, G. W., Kasper, J. D., & Spira, A. P. (2014) · International Psychogeriatrics · doi:10.1017/s1041610214001380 · Cited by 24
“, 2010) and even between DM and dementia (Cukierman et al., 2005; Schrijvers et al., 2010), others have not, or have found DM to be associated with dementias due to etiologies other than AD, such as vascular dementia (Curb et al.”
InfluentialSano, M. C., Zhu, C. W., Grossman, H. T., & Schimming, C. (2017) · Journal of the American Geriatrics Society · doi:10.1111/jgs.15014 · Cited by 24
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Glycemia and Cognitive Function in Metabolic Syndrome and Coronary Heart Disease
Avadhani, R., Fowler, K. M., Barbato, C., Thomas, S., Wong, W., Paul, C., Aksakal, M., Hauser, T. H., Weinger, K., & Goldfine, A. B. (2014) · The American Journal of Medicine · doi:10.1016/j.amjmed.2014.08.025 · Cited by 25
Cardiorenal Metabolic Syndrome and Diabetic Cognopathy
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Diabetes, Insulin and Alzheimer's Disease
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“Evidence from previous studies has highlighted the association between obesity, type 2 diabetes and cognitive dysfunction (8-10).”
L-3-n-butylphthalide attenuates cognitive deficits in db/db diabetic mice
Zhang, S., Ji, S., Bai, X., Yuan, F., Zhang, L., & Li, J. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0356-6 · Cited by 24
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“Although there are several reports on the association between type 1 diabetes and cognitive dysfunction,([9,17]) this association is yet to be robustly assessed by the larger population studies.”
BackgroundPsychische Erkrankungen und Diabetes mellitus (Update 2019)
Abrahamian, H., Kautzky‐Willer, A., Rießland-Seifert, A., Fasching, P., Ebenbichler, C. F., Kautzky, A., Hofmann, P., & Toplak, H. (2019) · Wiener klinische Wochenschrift · doi:10.1007/s00508-019-1458-9 · Cited by 23
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Blumenthal, J. A., Smith, P. J., Welsh-Bohmer, K. A., Babyak, M. A., Browndyke, J. N., Lin, P., Doraiswamy, P. M., Burke, J. R., Kraus, W. E., Hinderliter, A. L., et al. (2012) · Contemporary Clinical Trials · doi:10.1016/j.cct.2012.09.004 · Cited by 23
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“A growing body of evidence supports a critical role for insulin in cognitive function, and numerous studies have demonstrated an increased risk of cognitive impairment associated with both diabetes and insulin resistance (Cukierman et al., 2005; Luchsinger et al., 2004).”
BackgroundCerebral microbleeds, cognitive impairment, and MRI in patients with diabetes mellitus
Zhou, H., Yang, J., Xie, P., Dong, Y., You, Y., & Liu, J. (2017) · Clinica Chimica Acta · doi:10.1016/j.cca.2017.04.019 · Cited by 23
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Real-Time Breath Analysis in Type 2 Diabetes Patients During Cognitive Effort
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Zheng, Y., Ma, Q., Qi, X., Zhu, Z., & Wu, B. (2023) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2023.110976 · Cited by 23
Wennberg, A. M. V., Hagen, C. E., Gottesman, R. F., Zipunnikov, V. M., Kaufmann, C. N., Albert, M., Rebok, G. W., Kasper, J. D., & Spira, A. P. (2017) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2017.05.005 · Cited by 24
Links Between Adiponectin and Dementia: From Risk Factors to Pathophysiology
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“The latest cross-sectional and longitudinal researches have strongly demonstrated their association (Cukierman et al., 2005; Biessels et al., 2006).”
BackgroundGentreau, M., Rukh, G., Miguet, M., Clemensson, L. E., Alsehli, A. M., Titova, O. E., & Schiöth, H. B. (2023) · The Journals of Gerontology Series A · doi:10.1093/gerona/glad163 · Cited by 23
“Independently of statin use, poor glycemic control, and diabetes are well-established risk factors for cognitive decline and AD (19).”
BackgroundExendin-4 Prevents Memory Loss and Neuronal Death in Rats with Sporadic Alzheimer-Like Disease
Zago, A. M., Carvalho, F. B., Rahmeier, F. L., Santin, M., Guimarães, G. R., Gutierres, J. M., & Fernandes, M. D. C. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03698-w · Cited by 23
Type 2 diabetes mellitus, cognition and brain in aging: A brief review.
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“For instance, cardiovascular risk factors are associated with poorer cognitive functioning [Cukierman et al., 2005; Elias et al., 2006; Harrington et al., 2000; Kivipelto et al., 2001; Swan et al., 1998; Tilvis et al., 2004] and increased risk of dementia [Chao et al.”
BackgroundKera, T., Kawai, H., Hirano, H., Kojima, M., Watanabe, Y., Fujiwara, Y., Ihara, K., & Obuchi, S. P. (2018) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.13301 · Cited by 22
Diabetic Cognitive Dysfunction: From Bench to Clinic
Zhou, J., Zhang, Z., Zhou, H., & Qian, G. (2020) · Current Medicinal Chemistry · doi:10.2174/1871530319666190206225635 · Cited by 22
A 60-Year-Old Woman With Mild Memory Impairment
Ellison, J. M. (2008) · JAMA · doi:10.1001/jama.300.9.jrr80008 · Cited by 22
Zhang, Z., Lovato, J., Battapady, H., Davatzikos, C., Gerstein, H. C., Ismail-Beigi, F., Launer, L. J., Murray, A., Punthakee, Z., Tirado, A. A., et al. (2014) · Diabetes Care · doi:10.2337/dc14-0973 · Cited by 20
Self-citationGenome‐wide association studies: utility and limitations for research in physiology
Ciochetti, N. P., Lugli‐Moraes, B., da Silva, B. S., & Rovaris, D. L. (2023) · The Journal of Physiology · doi:10.1113/jp284241 · Cited by 25
“Diabetes mellitus, particularly type 2 diabetes, is an illness characterised by β-cell dysfunction and insulin insensitivity, which leads to a wide range of consequences including, but not exclusive to, cardiometabolic, vascular, neurological and nephrological disturbances (Cukierman et al., 2005).”
Faria, A. C. R. D. A., Dall'Agnol, J. F., Gouveia, A. M., de Paiva, C. I., Segalla, V. C., & Baena, C. P. (2022) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-022-00872-3 · Cited by 25
Shi, Y., Sun, X.-C., Sun, Y., Hou, L., Yao, M., Lian, K., Li, J., Lu, X., & Jiang, L. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.11.067 · Cited by 21
“Early prospective observational studies have shown that the risk of developing AD was almost doubled among those with DM (Ott et al., 1999; Cukierman et al., 2005).”
BackgroundCai, H., Li, G., Jiang, S., Yin, H., Liu, P., & Chen, L. (2019) · Journal of Gerontological Nursing · doi:10.3928/00989134-20190111-05 · Cited by 22
Sasaki‐Hamada, S., Hojo, Y., Koyama, H., Otsuka, H., & Oka, J. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.12891 · Cited by 23
“, 2002), and longitudinal research revealed that type 2 DM could result in accelerated cognitive decline (Allen et al., 2004; Cukierman et al., 2005).”
BackgroundCukierman‐Yaffe, T., Meron, M. K., Fruchter, E., Gerstein, H. C., Afek, A. B., Derazne, E., Tzur, D., Karasik, A., & Twig, G. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2012 · Cited by 21
Self-citationMatsumoto, C., Ogawa, H., Saito, Y., Okada, S., Soejima, H., Sakuma, M., Masuda, I., Nakayama, M., Doi, N., Jinnouchi, H., et al. (2019) · Diabetes Care · doi:10.2337/dc19-1188 · Cited by 20
“important risk factors for the development of both vascular and nonvascular dementia (4,5).”
BackgroundAltered Cerebellar-Cerebral Circuits in Patients With Type 2 Diabetes Mellitus
Zhang, D., Qi, F., Gao, J., Yan, X., Wang, Y., Tang, M., Zhe, X., Cheng, M., Wang, M., Xie, Q., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.571210 · Cited by 21
“Keywords: type 2 diabetes mellitus, resting-state fMRI, functional connectivity, cerebellum, subregion, neuroimaging INTRODUCTION Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer’s disease (AD) and vascular dementia (Curb et al., 1999; Luchsinger et al., 2001; Cukierman et al., 2005).”
BackgroundChanges in the structure, perfusion, and function of the hippocampus in type 2 diabetes mellitus
Li, M., Li, Y., Zhao, K., Tan, X. L., Chen, Y., Qin, C., Qiu, S., & Liang, Y. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1070911 · Cited by 20
“5–2-times cognitive decline with the onset of T2DM (Cukierman et al., 2005; Biessels et al., 2006).”
BackgroundNovel targets and therapies of metformin in dementia: old drug, new insights
Cui, W., Lv, C., Geng, P., Fu, M., Zhou, W., Xiong, M., & Li, T. X. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1415740 · Cited by 21
Nazaribadie, M., Amini, M., Ahmadpanah, M., Asgari, K., Jamlipaghale, S., & Nazaribadie, S. (2014) · Journal of Diabetes & Metabolic Disorders · doi:10.1186/2251-6581-13-27 · Cited by 20
“Introduction Several reports have indicated that diabetes may cause cognitive dysfunction [1-3] or an alternation in brain signals related to cognitive function [4-6] and accelerated cognitive decline [7,8].”
BackgroundDopamine 2 Receptor Genes Are Associated with Raised Blood Glucose in Schizophrenia
Lawford, B. R., Barnes, M., Morris, C. P., Noble, E. P., Nyst, P., Heslop, K., Young, R. M., Voisey, J., & Connor, J. P. (2016) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716644765 · Cited by 20
“Other evidence linking DRD2 SNPs to T2D has emerged recently, with rs6275 being associated with altered first phase glucose-stimulated insulin secretion in women.32 The CC genotype of rs6277 is also associated with increased consumption of sugars in men and women,33 and increased consumption of sugar-sweetened soft dr…”
BackgroundInfluentialChen, G., Zhang, X., Xing, Y., Dong, W., Cui, G., & Han, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.21282 · Cited by 20
van Gemert, T., Wölwer, W., Weber, K. S., Hoyer, A., Straßburger, K., Bohnau, N. T., Brüggen, M. A., Ovelgönne, K., Gössmann, E.-M., Burkart, V., et al. (2018) · Journal of Diabetes Research · doi:10.1155/2018/1470476 · Cited by 20
“Previous cross-sectional [1, 2] as well as longitudinal [3] studies showed that long-standing type 1 as well as type 2 diabetes mellitus is associated with a higher risk of impaired neurocognitive function and dementia.”
Huiying, Z., Guangying, C., & Zhou, S. (2019) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2019.1608197 · Cited by 20
Fenugreek seed extract ameliorates cognitive deficits in streptozotocin-induced diabetic rats
Kodumuri, P. K., Thomas, C., Jetti, R., & Pandey, A. K. (2019) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2018-0140 · Cited by 20
Sexual activity and cognitive decline in older age: a prospective cohort study
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“Individuals with diabetes are 1.5 times more likely to experience cognitive decline than individuals without diabetes (Cukierman et al. 2005).”
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“There is substantial evidence that Type 2 diabetes increases the risk for Alzheimer’s disease and related dementias (Craft 2005; Cukierman, Gerstein, and Williamson 2005; Luchsinger et al. 2001; Profenno, Porsteinsson, and Faraone 2010; Watson and Craft 2003).”
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Metadata
- Authors
- Cukierman, T., Gerstein, H. C., & Williamson, J. D.
- Affiliations
- Population Health Research Institute (CA)
- Wake Forest University Health Sciences (US)
- Corresponding author
- Cukierman, T.
- Venue
- Diabetologia
- Published
- 2005-11-08
- Volume
- 48
- Issue
- 12
- Pages
- 2460-2469
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2046949772
- Cited by
- 1,049
- References
- 90
- Citations by year
- 2026: 23 · 2025: 47 · 2024: 37 · 2023: 56 · 2022: 72 · 2021: 58 · 2020: 62 · 2019: 70 · 2018: 54 · 2017: 61 · 2016: 65 · 2015: 67 · 2014: 77 · 2013: 64 · 2012: 43
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- diabetes mellitus, cognitive decline, dementia, cognitive function, Mini-Mental State Examination, Digit Symbol Substitution Test, chronic complications of diabetes, longitudinal cohort
- MeSH terms
- Cognition, Cognition Disorders, Dementia, Diabetes Mellitus, Follow-Up Studies, Humans, Intelligence Tests, Longitudinal Studies, Neuropsychological Tests, Prospective Studies, Risk Factors, Odds Ratio, Diabetes Complications
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
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