Diabetes, glycaemia, and cognition—a secondary analysis of the Finnish Diabetes Prevention Study

Lehtisalo, Jenni; Lindström, Jaana; Ngandu, Tiia; Kivipelto, Miia; Ilanne‐Parikka, Pirjo; Keinänen‐Kiukaanniemi, Sirkka; Eriksson, Johan G.; Uusitupa, Matti; Tuomilehto, Jaakko; Luchsinger, José A.

doi:10.1002/dmrr.2679

Cited by 23 publications

(12 citation statements)

References 39 publications

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“…In the Diabetes Prevention Program Outcomes Study a lifestyle intervention similar to Look AHEAD was not associated with improved cognition 12 years after randomization, although higher HbA1c at the time of cognitive assessment was related to worse cognition (26). In the Finnish Diabetes Prevention study, the lifestyle intervention was also not related to cognitive performance 13 years after randomization and 9 years after the end of interventions (27), although higher glycaemia was related to worse cognitive performance (28). The Action to Control Cardiovascular Risk in Diabetes Memory study (ACCORD MIND), which enrolled 4393 men and women (46%) with diabetes who were slightly older, less overweight or obese, and had higher HbA1c than our sample, found no difference in cognitive outcomes at 40 months in an intensive glycemic control group compared to usual care (24).…”

Section: Discussionmentioning

confidence: 99%

Effect of a Long‐Term Intensive Lifestyle Intervention on Cognitive Function: Action for Health in Diabetes Study

Rapp

Luchsinger

Baker

et al. 2017

J American Geriatrics Society

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Objective To assess whether randomization to 10 years of lifestyle intervention to induce and maintain weight loss improves cognitive function. Research Design and Methods The Action for Health in Diabetes (Look AHEAD) enrolled overweight and obese individuals with type 2 diabetes, aged 45–76 years, into a randomized controlled clinical trial of an intensive lifestyle intervention for weight loss through reduced caloric intake and increased physical activity compared with a control condition of diabetes support and education. A standard battery of cognitive function tests was administered in 3,751 participants, 10–13 years following enrollment, by certified examiners who were masked to intervention assignment. The battery included the Modified Mini-Mental State Exam, Rey Auditory Verbal Learning Test, Digit Symbol Coding, Trail Making Test, and Modified Stroop Color-Word Test. Results Assignment to lifestyle intervention, compared with assignment to diabetes support and education, was not associated with significantly different overall (p=0.10) or domain-specific (all p >0.10) cognitive function. Results were fairly consistent across pre-specified groups, but there was some evidence of trends for differential intervention effects showing modest harm in ILI relative to DSE as BMI increased and among individuals with a history of cardiovascular disease. Cognitive function was not associated with changes in weight or fitness (all p >0.05). Conclusions Long-term behavioral weight loss intervention for overweight and obese adults with diabetes was not associated with cognitive benefit.

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Section: Discussionmentioning

confidence: 99%

Effect of a Long‐Term Intensive Lifestyle Intervention on Cognitive Function: Action for Health in Diabetes Study

Rapp

Luchsinger

Baker

et al. 2017

J American Geriatrics Society

Self Cite

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“…The cognition ancillary study of the FDPS also found that glycemia was related to worse cognitive performance, despite finding no association between the lifestyle intervention and cognitive performance (34). We can only speculate about explanations for this finding.…”

Section: Discussionmentioning

confidence: 99%

Metformin, Lifestyle Intervention, and Cognition in the Diabetes Prevention Program Outcomes Study

Luchsinger

Christophi

et al. 2017

Diabetes Care

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OBJECTIVEWe examined the association of the Diabetes Prevention Program (DPP) intervention arms (lifestyle intervention, metformin, and placebo) with cognition in the Diabetes Prevention Program Outcomes Study (DPPOS). We also examined metformin use, incident type 2 diabetes, and glycemia as exposures.RESEARCH DESIGN AND METHODSThe DPP lasted 2.8 years, followed by a 13-month bridge to DPPOS. Cognition was assessed in DPPOS years 8 and 10 (12 and 14 years after randomization) with the Spanish English Verbal Learning Test (SEVLT), letter fluency and animal fluency tests, Digit Symbol Substitution Test (DSST), and a composite cognitive score.RESULTSA total of 2,280 participants (749 lifestyle, 776 metformin, and 755 placebo) aged 63.1 ± 10.7 years underwent cognitive assessments; 67.7% women, 54.6% non-Hispanic white, 20.7% non-Hispanic black, 14.6% Hispanic, 5.5% American Indian, and 4.6% Asian; 26.6% were homozygous or heterozygous for APOE-ε4. At the time of cognitive assessment, type 2 diabetes was higher in the placebo group (57.9%; P < 0.001) compared with lifestyle (47.0%) and metformin (50.4%). Metformin exposure was higher in the metformin group (8.72 years; P < 0.001) compared with placebo (1.43 years) and lifestyle (0.96 years). There were no differences in cognition across intervention arms. Type 2 diabetes was not related to cognition, but higher glycated hemoglobin at year 8 was related to worse cognition after confounder adjustment. Cumulative metformin exposure was not related to cognition.CONCLUSIONSExposure to intensive lifestyle intervention or metformin was not related to cognition among DPPOS participants. Higher glycemia was related to worse cognitive performance. Metformin seemed cognitively safe among DPPOS participants.

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“…This suggests that, in addition to protecting against cardiovascular disease, diabetes, obesity, and hypertension, healthful diets and regular physical exercise are neuroprotective and guard against mild cognitive impairment and AD [97, 145], and also positively impact neuronal plasticity [146]. Epidemiological data further suggest that the “Mediterranean diet” which is rich in fruits, vegetables and extra virgin olive oil, provides neuroprotection with aging [147], and that tight regulation of glycemia in diabetics helps preserve cognitive function [148]. In contrast, diets rich in simple sugars, particularly fructose, increase rates of Type 2 Diabetes Mellitus, which in turn, enhances risk for AD [149].…”

Section: Therapeutic Strategies For Abrogating Brain Insulin Deficimentioning

confidence: 99%

Insulin Resistance and Neurodegeneration: Progress Towards the Development of New Therapeutics for Alzheimer’s Disease

Monte

2016

Drugs

220

153

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Alzheimer’s disease (AD) should be regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, and overlapping with the molecular, biochemical, pathophysiological, and metabolic dysfunctions occurring in diabetes mellitus, non-alcoholic fatty liver disease, and metabolic syndrome. Although most of the diagnostic and therapeutic approaches over the past several decades have focused on amyloid-beta (Aβ42) and aberrantly phosphorylated tau, which could be caused by consequences of brain insulin resistance, the broader array of pathologies including white matter atrophy with loss of myelinated fibrils and leukoaraiosis, non-Aβ42 microvascular disease, dysregulated lipid metabolism, mitochondrial dysfunction, astrocytic gliosis, neuro-inflammation, and loss of synapses vis-à-vis growth of dystrophic neurites, is not readily accounted for by Aβ42 accumulations, but could be explained by dysregulated insulin/IGF-1 signaling with attendant impairments in signal transduction and gene expression. This review covers the diverse range of brain abnormalities in AD and discusses how insulins, incretins, and insulin sensitizers could be utilized to treat at different stages of neurodegeneration.

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Diabetes, glycaemia, and cognition—a secondary analysis of the Finnish Diabetes Prevention Study

Cited by 23 publications

References 39 publications

Effect of a Long‐Term Intensive Lifestyle Intervention on Cognitive Function: Action for Health in Diabetes Study

Effect of a Long‐Term Intensive Lifestyle Intervention on Cognitive Function: Action for Health in Diabetes Study

Metformin, Lifestyle Intervention, and Cognition in the Diabetes Prevention Program Outcomes Study

Insulin Resistance and Neurodegeneration: Progress Towards the Development of New Therapeutics for Alzheimer’s Disease

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