Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies

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.”

In the paper

“The odds of future dementia increased 1.6-fold (95% CI 1.4 -1.8).”

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.”

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.”

What the sources say

• Not checked yetcites [46 -70]

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.”

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.”

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).”

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

In the paper

“In these studies, diabetes status predicted an odds ratio for cognitive decline that ranged from 0.7 to 4.4.”

In the paper

“Three studies reported a decline ranging from 1.3 to 1.4% per year in people with diabetes.”

In the paper

“Moreover, two of the studies included in this review reported that participants with impaired fasting glucose or impaired glucose tolerance experience more cognitive decline than participants without, further supporting a link between cognitive decline and hyperglycaemia [51, 69, 70].”

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
• 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

In the paper

“This systematic overview of prospective studies supports the conclusion that, compared to people without diabetes, people with diabetes have: (1) a greater rate of decline in cognitive function; (2) a 1.5-fold greater risk of cognitive decline; and (3) a 1.6-fold greater risk of future dementia.”

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).”

In the paper

“The ratio of the relative change in score from baseline in people with diabetes compared to those without diabetes ranged from 1.2 to 1.6.”

In the paper

“This systematic overview of prospective studies supports the conclusion that, compared to people without diabetes, people with diabetes have: (1) a greater rate of decline in cognitive function; (2) a 1.5-fold greater risk of cognitive decline; and (3) a 1.6-fold greater risk of future dementia.”

• Also stated in: § Measures of cognitive function · p. 6 · plain

  “Overall, people with diabetes were 1.6 times more likely to develop all-cause dementia than people without diabetes (95% CI 1.4 -1.8).”

In the paper

“Individuals with diabetes experienced a consistently greater decline or lesser improvement than those without diabetes.”

In the paper

“Interestingly, the included studies reported a similar degree of cognitive decline, despite differences in analytic approaches and cognitive assessment tools.”

In the paper

“This systematic overview of prospective studies supports the conclusion that, compared to people without diabetes, people with diabetes have: (1) a greater rate of decline in cognitive function; (2) a 1.5-fold greater risk of cognitive decline; and (3) a 1.6-fold greater risk of future dementia.”

In the paper

“Test for heterogeneity: chi square=4.02, df =4 ( p =0.40), I 2 =0.6%”

In the paper

“This possibility is supported by the fact that the overall estimated effect of the MMSE/3MS was smaller than the overall estimate obtained from studies that used the DSS.”

In the paper

“Despite this relationship, there is no evidence to date that diabetes management affects the rate or nature of cognitive dysfunction.”

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

In the paper

“| Total (95% CI) | 394 | 5866 | 1.7 (1.3, 2.3) |”

In the paper

“Studies reporting the development of future dementia of these reported that people with diabetes had a higher risk of all-cause dementia than people without diabetes [56, 58, 64, 65, 67].”

What the sources say

• Not checked yetcites [56] Ott A, Stolk RP, van HF, Pols HA, Hofman A, Breteler MM (1999) Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 53:1937–1942 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 [64] MacKnight C, Rockwood K, Awalt E, McDowell I (2002) Diabetes mellitus and the risk of dementia, Alzheimer's disease and vascular cognitive impairment in the Canadian Study of Health and Aging. Dement Geriatr Cogn Disord 14:77–83 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 [67] Peila R, Rodriguez BL, Launer LJ, Honolulu–Asia AS (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu–Asia Aging Study. Diabetes 51:1256–1262 source

In the paper

“Despite these differences, only two studies reported that diabetes non-significantly reduced the risk for cognitive decline.”

In the paper

“Studies were similar with respect to four of the quality measures used.”

In the paper

“Recent evidence from several epidemiological studies suggests that it is also a risk factor for cognitive dysfunction [3 -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 [5] Lobo A, Launer LJ, Fratiglioni L et al (2000) Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic diseases in the elderly research group. Neurology 54(Suppl 5):S4–S9
• Not checked yetcites [6] Stewart R, Liolitsa D (1999) Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med 16:93–112 source

In the paper

“However, many of these studies were cross-sectional and were thus unable to provide estimates of diabetes as a risk factor for future cognitive dysfunction.”

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 [5] Lobo A, Launer LJ, Fratiglioni L et al (2000) Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic diseases in the elderly research group. Neurology 54(Suppl 5):S4–S9
• Not checked yetcites [6] Stewart R, Liolitsa D (1999) Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med 16:93–112 source

In the paper

“Indeed, only one [7] of the review articles that summarised the available data pertaining to this relationship [4, 6 -11] provided a quantitative estimate.”

What the sources say

• Not checked yetcites [7] Awad N, Gagnon M, Messier C (2004) The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function. J Clin Exp Neuropsychol 26:1044–1080 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
• Not checked yetcites [8] Biessels GJ, van der Heide LP, Kamal A, Bleys RL, Gispen WH (2002) Ageing and diabetes: implications for brain function. Eur J Pharmacol 441:1–14 source
• Not checked yetcites [9] Strachan MW, Frier BM, Deary IJ (2003) Type 2 diabetes and cognitive impairment. Diabet Med 20:1–2 source
• 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
• Not checked yetcites [11] Strachan MW, Frier BM, Deary IJ (1997) Cognitive assessment in diabetes: the need for consensus. Diabet Med 14:421–422 source

In the paper

“Loss to follow-up ranged from 8 to 27%.”

In the paper

“Second, depression occurs more frequently in people with diabetes [73] and is difficult to differentiate clinically from dementia and early cognitive decline [74 -77].”

What the sources say

• Not checked yetcites [73] Anderson RJ, Freedland KE, Clouse RE, Lustman PJ (2001) The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 24:1069–1078 source

In the paper

“Indeed, in one study, which did report diabetes status of individuals lost to follow-up, diabetic participants had a higher mortality and/ or lower follow-up rates than those without diabetes [55].”

What the sources say

• Not checked yetcites [55] Tilvis RS, Kahonen-Vare MH, Jolkkonen J, Valvanne J, Pitkala KH, Strandberg TE (2004) Predictors of cognitive decline and mortality of aged people over a 10-year period. J Gerontol A Biol Sci Med Sci 59:268–274 source

In the paper

“Indeed, intensive treatment regimens that were associated with increased hypoglycaemic episodes in individuals with type 1 diabetes did not adversely affect cognition [78].”

What the sources say

• Not checked yetcites [78] Reichard P, Pihl M (1994) Mortality and treatment side-effects during long-term intensified conventional insulin treatment in the Stockholm diabetes intervention study. Diabetes 43:313–317 source

In the paper

“In the Framingham Study, 2,123 subjects aged 55 to 88 completed a neuropsychological test battery during either the 14th or 15th biennial examination. People with diabetes status were more likely to achieve scores below the 25th percentile on most tests than were non-diabetic individuals.”

What the sources say

• Not checked yetcites [71] Elias PK, Elias MF, D'Agostino RB et al (1997) NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham Study. Diabetes Care 20:1388–1395 source

In the paper

“Furthermore, these studies probably underestimated the impact of diabetes on cognitive function because they generally excluded cognitively impaired individuals at baseline, and may therefore have ' selected for ' healthier individuals with lower risk of cognitive decline.”

In the paper

“Post mortem studies of senile plaques from the brains of people with Alzheimer dementia found metabolic oxidation products associated with hyperglycaemia [79, 80].”

What the sources say

• Not checked yetcites [79] Horie K, Miyata T, Yasuda T et al (1997) Immunohistochemical localization of advanced glycation end products, pentosidine, and carboxymethyllysine in lipofuscin pigments of Alzheimer's disease and aged neurons. Biochem Biophys Res Commun 236:327–332 source
• Not checked yetcites [80] Vlassara H, Bucala R, Striker L (1994) Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest 70:138–151

In the paper

“Second, depression occurs more frequently in people with diabetes [73] and is difficult to differentiate clinically from dementia and early cognitive decline [74 -77].”

What the sources say

• Not checked yetcites [74] Swainson R, Hodges JR, Galton CJ et al (2001) Early detection and differential diagnosis of Alzheimer's disease and depression with neuropsychological tasks. Dement Geriatr Cogn Disord 12:265–280 source
• Not checked yetcites [75] Comijs HC, van TT, Geerlings SW et al (2004) Do severity and duration of depressive symptoms predict cognitive decline in older persons? Results of the Longitudinal Aging Study Amsterdam. Aging Clin Exp Res 16:226–232 source
• Not checked yetcites [76] Paterniti S, Verdier-Taillefer MH, Dufouil C, Alperovitch A (2002) Depressive symptoms and cognitive decline in elderly people. Longitudinal study. Br J Psychiatr 181:406–410 source
• Not checked yetcites [77] Jorm AF (2000) Is depression a risk factor for dementia or cognitive decline? A review. Gerontology 46:219–227 source

In the paper

“They are also supported by the large Framingham study [71] and the Adult Health Study [72].”

What the sources say

• Not checked yetcites [71] Elias PK, Elias MF, D'Agostino RB et al (1997) NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham Study. Diabetes Care 20:1388–1395 source
• 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

In the paper

“Thus, a relationship between cognitive change and diabetes may be mediated through cerebrovascular disease.”

In the paper

“However, at least one of the studies [54] reported an association between diabetes and cognitive decline even after adjustment for depression.”

What the sources say

• 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

In the paper

“Nevertheless, the results of the prospective studies summarised here suggest that cognitive dysfunction should be considered as yet another chronic consequence and disabling manifestation of diabetes.”

In the paper

“This instrument (which was designed as a tool for assessing global cognitive function) has a limited ability to detect changes in specific cognitive domains such as attention and processing speed [17, 82].”

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 [82] Nasreddine ZS, Phillips NA, Bedirian V et al (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriat Soc 53:695–699 source

In the paper

“The consistency of our results, despite the differences in the studies, highlights the robustness of the conclusion that diabetes is indeed a risk factor for cognitive decline.”

In the paper

“Finally, prospective epidemiological studies also show a relationship between cognitive decline and clinical markers associated with hyperglycaemia, e.g. use of glucose-lowering medication, diabetes duration and diabetes complications [46, 48, 49, 54, 56, 64].”

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 [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 [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 [56] Ott A, Stolk RP, van HF, Pols HA, Hofman A, Breteler MM (1999) Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 53:1937–1942 source
• Not checked yetcites [64] MacKnight C, Rockwood K, Awalt E, McDowell I (2002) Diabetes mellitus and the risk of dementia, Alzheimer's disease and vascular cognitive impairment in the Canadian Study of Health and Aging. Dement Geriatr Cogn Disord 14:77–83 source