Impaired insulin secretion increases the risk of Alzheimer disease

Rönnemaa, Elina; Zethelius, Björn; Sundelöf, Johan; Sundström, Johan; Degerman-Gunnarsson, Malin; Berne, Christian; Lannfelt, Lars; Kilander, Lena

doi:10.1212/01.wnl.0000310646.32212.3a

Cited by 218 publications

(151 citation statements)

References 31 publications

(15 reference statements)

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“…In the present study, EIR was measured in an OGTT at 71 years. The findings of an association between impaired EIR and Alzheimer's disease in the present study are in line with our previous report, in which the impaired acute insulin response measured at an intravenous glucose tolerance test at age 50 was associated with Alzheimer's disease later in life [9]. Thus, this risk marker is stable at both middle and higher ages and can be detected in an OGTT, although this method is less reproducible than an intravenous glucose tolerance test.…”

Section: Discussionsupporting

confidence: 92%

“…The association between low EIR and Alzheimer's disease was stronger in men without the APOE ε4 allele than in those with this allele, confirming our previous results from this population [9]. An impaired insulin response seems to be an important risk factor for Alzheimer's disease in the absence of the high-risk allele.…”

Section: Discussionsupporting

confidence: 88%

“…A low acute insulin response in an intravenous glucose tolerance test in midlife was associated with an increased risk of Alzheimer's disease during a 32-year follow-up [9]. Furthermore, decreased peripheral insulin levels were associated with Alzheimer's disease-related brain atrophy in a cross-sectional study [10], and such patients have also been found to have reduced insulin concentrations in the brain and the cerebrospinal fluid [11].…”

Section: Introductionmentioning

confidence: 99%

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Glucose metabolism and the risk of Alzheimer’s disease and dementia: a population-based 12 year follow-up study in 71-year-old men

et al. 2009

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Aims/hypothesis Accumulating evidence suggests that diabetes increases the risk of dementia, but few studies have addressed possible mechanisms underlying this relationship. The aim of our study was to investigate the longitudinal association of glucose metabolism, insulin secretion and insulin action with the development of Alzheimer's disease and vascular dementia. Methods The Uppsala Longitudinal Study of Adult Men is an ongoing observational study in Sweden in which 1,125 men aged 71 years and free from dementia underwent an OGTT and a euglycaemic insulin clamp between 1990 and 1995. During a median follow-up of 12 years, 257 persons developed dementia or cognitive impairment, of whom 81 had Alzheimer's disease and 26 vascular dementia. Associations were analysed with the Cox proportional hazards method. Results Low early insulin response to oral glucose challenge, but not low insulin sensitivity, was associated with a higher risk of Alzheimer's disease (HR for 1 SD decrease 1.32; 95% CI 1.02, 1.69) after adjustment for diabetes, blood pressure, body mass index, cholesterol, smoking and educational level. Low insulin sensitivity was associated with a higher risk of vascular dementia (HR for 1 SD decrease 1.55; 95% CI 1.02, 2.35), but not after multiple adjustments. Diabetes increased the risk of any dementia and cognitive impairment by 63%. Conclusions/interpretation In this community-based study, low early insulin response was associated with increased risk of subsequent Alzheimer's disease, whereas low insulin sensitivity was not. Vascular dementia was not related to early insulin response. We suggest that glucometabolic disturbances are linked differentially to the pathogenesis of these two main dementia subtypes.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Glucose metabolism and the risk of Alzheimer’s disease and dementia: a population-based 12 year follow-up study in 71-year-old men

et al. 2009

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“…A longitudinal study on 2,322 participants, followed up for 32 years reported that impaired insulin response in midlife was associated with an increased risk of AD [61]. Van Oijen and colleagues reported CD in older women with high levels of fasting insulin secretion in midlife, in comparison to those with lower levels of insulin secretion [62].…”

Section: Discussionmentioning

confidence: 99%

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

Tortelli

Lozupone

Guerra

et al. 2017

JAD

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Abstract. Among metabolic syndrome components, the effects of higher plasma glucose levels on cognitive decline (CD) have been considered in few studies. We evaluated the associations among midlife glycemia, total cholesterol, high-density lipoprotein cholesterol, triglycerides, midlife insulin resistance [homeostasis model assessment for insulin resistance (HOMAindex)], and CD in the older subjects of the population-based MICOL Study (Castellana Grotte, Italy) at baseline (M1) and at follow-ups seven (M2) and twenty years later (M3). At M1, a dementia risk score and a composite cardiovascular risk score for dementia were calculated. For 797 subjects out of 833, we obtained a Mini-Mental State Examination (MMSE) score at M3, subdividing these subjects in three cognitive functioning subgroups: normal cognition, mild CD, and moderate-severe CD. Mean fasting glycemia at baseline was significantly higher in moderate-severe CD subgroup (114.6 ± 71.4 mg/dl) than in the normal cognition subgroup (101.2 ± 20.6). Adjusting for gender, age, and other metabolic components, higher fasting glycemia values both at M1 [odds ratio (OR) = 1.31; 95% confidence interval (CI): 1.08-1.59] and M2 (OR = 1.26; 95% CI: 1.01-1.57) were associated with an increased risk of moderate-severe CD. Mean HOMA index value was significantly higher in the moderate-severe CD subgroup (5.7 ± 9.4) compared to the normal cognition subgroup (2.9 ± 1.4) at M1. The dementia risk probability (MMSE < 24) increased moving through higher categories of the dementia risk score and decreased as long as the cardiovascular score increased. The present findings highlighted the indication to control blood glucose levels, regardless of a diagnosis of diabetes mellitus, as early as midlife for prevention of late-life dementia.

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“…Moreover, borderline conditions, prediabetes or impaired glucose tolerance are also related to an increased risk of AD and other dementias in very old people 75 . This relationship may be partly explained by diabetic comorbidities such as hypertension and dyslipidaemia [76][77][78] . A relationship was also found between a higher prevalence of AD in an elderly population in Finland 79 , although an analytical study of a multiethnic cohort of the elderly in the USA found no association between the metabolic syndrome and either the prevalence or incidence of AD, despite the fact that two components of the syndrome, i.e.…”

Section: Diabetes Mellitusmentioning

confidence: 99%

Epidemiological of and risk factors for Alzheimer's disease: A review

Povová

Ambrož²,

Bar³

et al. 2012

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

110

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Background. Alzheimer's disease (AD) is the most common form of dementia. It is a degenerative, incurable and terminal disease. The increasing prevalence of AD is, among other reasons, due to population aging, which is, to a certain extent, seen worldwide. Continuous advances in health care keep increasing life expectancy. Official statistics are likely to significantly underestimate the actual prevalence of AD. Alzheimer's disease represents an important public health problem. Its aetiology is still unknown and for this reason, it is necessary to study all potential risk factors which may contribute to the development of this disease. Methods. We searched original and review articles addressing Alzheimer´s disease using key words Alzheimer's disease, epidemiology, risk factors and prevention. We found and used one hundred and four references. Conclusions. Based on epidemiological studies, genetic studies, neuroimaging methods and neuropathology research, three basic etiological hypotheses of the development of AD have been formulated: genetic, vascular and psychosocial. At present, the level of evidence is insufficient for the etiological role of other factors, such as nutrition, occupational exposure to various substances and inflammation. From the point of view of early diagnosis and application of primary or secondary prevention principles, genetic factors are the most important.

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Impaired insulin secretion increases the risk of Alzheimer disease

Abstract: In this longitudinal study, impaired acute insulin response at midlife was associated with an increased risk of Alzheimer disease (AD) up to 35 years later suggesting a causal link between insulin metabolism and the pathogenesis of AD.

Cited by 218 publications

References 31 publications

Glucose metabolism and the risk of Alzheimer’s disease and dementia: a population-based 12 year follow-up study in 71-year-old men

Glucose metabolism and the risk of Alzheimer’s disease and dementia: a population-based 12 year follow-up study in 71-year-old men

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

Epidemiological of and risk factors for Alzheimer's disease: A review

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