scholarly journals Metformin-use is associated with slowed cognitive decline and reduced incident dementia in older adults with type 2 diabetes mellitus: the Sydney Memory and Ageing Study

2020 ◽  
Author(s):  
Katherine Samaras ◽  
Steve Makkar ◽  
John D. Crawford ◽  
Nicole A. Kochan ◽  
Wei Wen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Executive Function ◽  
Cognitive Decline ◽  
Dementia Risk ◽  
Incident Dementia ◽  
Ageing Study ◽  
Global Cognition

<b>Objective:</b> Type 2 diabetes mellitus (diabetes) is characterized by accelerated cognitive decline and higher dementia risk. Controversy exists regarding the impact of metformin which is associated with both increased and decreased dementia rates. The objective of this study was to determine the association of metformin-use with incident dementia and cognitive decline over 6 years in diabetes, compared to those not receiving metformin and those without diabetes. <p><b>Research</b> <b>Design and Methods</b>: Prospective observational study of N=1037 non-demented community-dwelling older participants aged 70-90 at baseline (the Sydney Memory and Ageing Study). Exclusion criteria were dementia, major neurological or psychiatric disease or progressive malignancy. Neuropsychological testing measured cognitive function every two years; a battery of tests measured executive function, memory, attention/speed, language and visuospatial function individually and to a construct of global cognition. Incident dementia was ascertained by a multidisciplinary panel. Total brain, hippocampal and parahippocampal volumes were measured by magnetic resonance at baseline and 2 years (n=526). Data were analyzed by linear mixed modeling, including the covariates of age, sex, education, body mass index, heart disease, hypertension, stroke, smoking and apolipoprotein Ee4 carriage. </p> <p><b>Results</b>: Of n=1037, 123 had diabetes; 67 received metformin (DM+MF) and were demographically similar to those not (DM-noMF) and participants without diabetes (no-DM). DM+MF had significantly slower global cognition and executive function decline compared to DM-noM. Incident dementia was significantly higher in DM-noMF compared to DM+MF (OR 5.29, 95%CI 1.17-23.88, p=0.05).</p> <p><b>Conclusions</b>: Older people with diabetes receiving metformin have slower cognitive decline and lower dementia risk. Large randomized studies in people with and without diabetes will determine whether these associations can be attributed to metformin. </p>

scholarly journals Metformin-use is associated with slowed cognitive decline and reduced incident dementia in older adults with type 2 diabetes mellitus: the Sydney Memory and Ageing Study

2020 ◽  
Author(s):  
Katherine Samaras ◽  
Steve Makkar ◽  
John D. Crawford ◽  
Nicole A. Kochan ◽  
Wei Wen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Executive Function ◽  
Cognitive Decline ◽  
Dementia Risk ◽  
Incident Dementia ◽  
Ageing Study ◽  
Global Cognition

<b>Objective:</b> Type 2 diabetes mellitus (diabetes) is characterized by accelerated cognitive decline and higher dementia risk. Controversy exists regarding the impact of metformin which is associated with both increased and decreased dementia rates. The objective of this study was to determine the association of metformin-use with incident dementia and cognitive decline over 6 years in diabetes, compared to those not receiving metformin and those without diabetes. <p><b>Research</b> <b>Design and Methods</b>: Prospective observational study of N=1037 non-demented community-dwelling older participants aged 70-90 at baseline (the Sydney Memory and Ageing Study). Exclusion criteria were dementia, major neurological or psychiatric disease or progressive malignancy. Neuropsychological testing measured cognitive function every two years; a battery of tests measured executive function, memory, attention/speed, language and visuospatial function individually and to a construct of global cognition. Incident dementia was ascertained by a multidisciplinary panel. Total brain, hippocampal and parahippocampal volumes were measured by magnetic resonance at baseline and 2 years (n=526). Data were analyzed by linear mixed modeling, including the covariates of age, sex, education, body mass index, heart disease, hypertension, stroke, smoking and apolipoprotein Ee4 carriage. </p> <p><b>Results</b>: Of n=1037, 123 had diabetes; 67 received metformin (DM+MF) and were demographically similar to those not (DM-noMF) and participants without diabetes (no-DM). DM+MF had significantly slower global cognition and executive function decline compared to DM-noM. Incident dementia was significantly higher in DM-noMF compared to DM+MF (OR 5.29, 95%CI 1.17-23.88, p=0.05).</p> <p><b>Conclusions</b>: Older people with diabetes receiving metformin have slower cognitive decline and lower dementia risk. Large randomized studies in people with and without diabetes will determine whether these associations can be attributed to metformin. </p>

scholarly journals SAT-LB115 Metformin-Use Is Associated With Slowed Cognitive Decline and Reduced Incident Dementia in Older Adults With Type 2 Diabetes Mellitus: The Sydney Memory and Ageing Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Katherine Samaras ◽  
Steve Makkar ◽  
John D Crawford ◽  
Nicole A Kochan ◽  
Wei Wen ◽  
...  
Keyword(s):  
Older Adults ◽  
Heart Disease ◽  
Executive Function ◽  
Older People ◽  
Cognitive Decline ◽  
Community Dwelling ◽  
Incident Dementia ◽  
Ageing Study ◽  
Global Cognition ◽  
Rate Of Decline

Abstract Background Metformin use in diabetes has been associated with both increased and decreased dementia rates in observational studies of people with diabetes. Objective: To examine changes in global cognition and specific cognitive domains over 6 years in older adults with diabetes treated with metformin, compared to other glucose lowering medications, and to people without diabetes. Methods Data were examined from the Sydney Memory and Ageing Study, a prospective observational study of 6 years duration of 1037 non-demented community-dwelling elderly aged 70-90 at baseline, derived from a compulsory electoral roll. Neuropsychological testing was performed every 2 years with domain measures of memory, executive function, language, visuospatial function, attention and processing speed and a composite of global cognition. Data were analysed by linear mixed modelling, including age, sex, education, body mass index, heart disease, diabetes, hypertension, stroke, smoking and apolipoprotein E ε4 carriage as covariates. Results: At baseline, 123 participants had diabetes (DM) with 67 receiving metformin (DM+MF) who were similar in demographics to those not receiving metformin (DM-noMF) and those without diabetes (no-DM). Participants with diabetes had higher BMI, lower HDL- and LDL-cholesterol and more prevalent heart disease, hypertension and smoking, compared to no-DM. Over 6-years, DM+MF participants had significantly slower rates of decline in global cognition and executive function, compared to DM-noMF, adjusted for covariates. The rate of decline for each cognitive domain was similar between DM+MF and controls. No impact was found in analyses examining interactions with sex, ApoEε4 carriage or hyperlipidemia. No difference was found in the rate of decline in brain volumes between the groups over 2 years. Incident dementia was significantly higher in DM-noMF, compared to DM+MF (adjusted OR 5.29 [95% CI 1.17-23.88], p,0.05), whereas risk of incident dementia was similar between DM+MF and participants without diabetes. Conclusions: In older people with diabetes receiving metformin, rates of cognitive decline and dementia were similar to that found in people without diabetes and significantly less than that found in people with diabetes not receiving metformin. Large randomized studies in people with and without diabetes are required to determine whether these associations can be attributed to metformin alone or if other factors explain these observations. Future studies will clarify if this cheap and safe medication can be repurposed for prevention of cognitive decline in older people.

scholarly journals Deficits in hippocampal neurogenesis in obesity-dependent and -independent type-2 diabetes mellitus mouse models

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jacqueline A. Bonds ◽  
Aashutosh Shetti ◽  
Terilyn K. L. Stephen ◽  
Marcelo G. Bonini ◽  
Richard D. Minshall ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Growth Factor ◽  
Cognitive Decline ◽  
Leptin Receptor ◽  
Memory Function ◽  
Growth Factor Receptor ◽  
Hippocampal Neurogenesis

Abstract Hippocampal neurogenesis plays an important role in learning and memory function throughout life. Declines in this process have been observed in both aging and Alzheimer’s disease (AD). Type 2 Diabetes mellitus (T2DM) is a disorder characterized by insulin resistance and impaired glucose metabolism. T2DM often results in cognitive decline in adults, and significantly increases the risk of AD development. The pathways underlying T2DM-induced cognitive deficits are not known. Some studies suggest that alterations in hippocampal neurogenesis may contribute to cognitive deterioration, however, the fate of neurogenesis in these studies is highly controversial. To address this problem, we utilized two models of T2DM: (1) obesity-independent MKR transgenic mice expressing a mutated form of the human insulin-like growth factor 1 receptor (IGF-1R) in skeletal muscle, and (2) Obesity-dependent db/db mice harboring a mutation in the leptin receptor. Our results show that both models of T2DM display compromised hippocampal neurogenesis. We show that the number of new neurons in the hippocampus of these mice is reduced. Clone formation capacity of neural progenitor cells isolated from the db/db mice is deficient. Expression of insulin receptor and epidermal growth factor receptor was reduced in hippocampal neurospheres isolated from db/db mice. Results from this study warrant further investigation into the mechanisms underlying decreased neurogenesis in T2DM and its link to the cognitive decline observed in this disorder.

scholarly journals Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline

Stroke ◽  
2017 ◽  
Vol 48 (9) ◽  
pp. 2368-2374 ◽  
Author(s):  
Einor Ben Assayag ◽  
Roy Eldor ◽  
Amos D. Korczyn ◽  
Efrat Kliper ◽  
Shani Shenhar-Tsarfaty ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Function ◽  
Cognitive Decline ◽  
Impaired Renal Function

scholarly journals Brain Activation during Memory Encoding in Type 2 Diabetes Mellitus: A Discordant Twin Pair Study

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Amanda G. Wood ◽  
Jian Chen ◽  
Christopher Moran ◽  
Thanh Phan ◽  
Richard Beare ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cognitive Decline ◽  
Brain Activation ◽  
Cognitive Test ◽  
Angular Gyrus ◽  
Neuronal Dysfunction ◽  
Memory Encoding

Type 2 diabetes mellitus increases the risk of dementia and neuronal dysfunction may occur years before perceptible cognitive decline. We aimed to study the impact of type 2 diabetes on brain activation during memory encoding in middle-aged people, controlling for age, sex, genes, and early-shared environment. Twenty-two twin pairs discordant for type 2 diabetes mellitus (mean age 60.9 years) without neurological disease were recruited from the Australian Twin Registry (ATR) and underwent functional magnetic resonance imaging (fMRI) during a memory encoding task, cognitive tests, and structural MRI. Type 2 diabetes was associated with significantly reduced activation in left hemisphere temporoparietal regions including angular gyrus, supramarginal gyrus, and middle temporal gyrus and significantly increased activation in bilateral posteriorly distributed regions. These findings were present in the absence of within-pair differences in standard cognitive test scores, brain volumes, or vascular lesion load. Differences in activation were more pronounced among monozygotic (MZ) pairs, with MZ individuals with diabetes also displaying greater frontal activation. These results provide evidence for preclinical memory-related neuronal dysfunction in type 2 diabetes. They support the search for modifiable later-life environmental factors or epigenetic mechanisms linking type 2 diabetes and cognitive decline.

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