Swedish National Patient Register
The Patient Register provided records on inpatient diagnoses since 1998 and specialized outpatient visits since 2001 until December 31, 2017. Diagnoses were coded according to the 10th version of the International Classification of Diseases .
Diagnosis of diabetes was determined when the ICD-10 codes E10E14 occurred in the Patient Register or antidiabetic drug dispensation was observed in the Swedish Prescribed Drug Register prior to and including the date of dementia diagnosis. Subsequently, diabetes was grouped into three typestype 1 diabetes, type 2 diabetes, and other/unspecified diabetes . Only patients with type 2 diabetes and other/unspecified types were included for the analyses.
Baseline diabetes duration was based on the difference between the date of dementia diagnosis and the date of the earliest record of diabeteseither in the Patient Register where the diagnosis of diabetes occurred or the earliest dispensation date of ATC code A10 from the Drug Register, whichever came first.
To adjust for the effect of additional chronic diseases, we created a baseline comorbidity index as described by Charlson et al. , using the algorithm described by Quan et al. as a weighted sum of diagnosed chronic disorders up to and including the date of dementia diagnosis. Renal disease was not included in the index and was extracted as a separate variable. Diabetes and dementia variables were omitted from the index.
How Harmful Might Metformin Be To The Brain
As reported by Medscape Medical News, Yi-Chun Kuan and team conducted a cohort study to follow a total 9,300 patients with type 2 diabetes in Taiwan for up to 12 years. They checked records for these patients from the National Health research database of Taiwan including 4,651 who had metformin prescriptions and 4651 matched controls who didnt take any metformin.
Dr. Kuan told Medscape they adjusted for age, sex, and diabetes severity and that despite this, the cumulative incidences of Parkinsons and dementia were significantly higher for our metformin cohort at 12 years.
In fact, the risk for Parkinsons disease or Alzheimers dementia went up over 50 percent during a 12 year period in those who took metformin when compared to those who did not. Researchers also found that outcome risks increased progressively with higher dosage and longer duration of treatment.
Dr. Yi-Chun Kuan said, Wed heard about a possible protective effect from metformin. However, we found the reverse, and she added that large-scale, prospective studies would need to be done in other countries to get clarification of the results.
Another detail the researchers noted was that outcomes increased the longer a patient was on metformin and the higher the metformin dose they took, especially with use for more than 300 days and doses greater than 240 g.
Magnetic Resonance Imaging Data Acquisition Interpretation And Evaluation
Magnetic resonance imaging examination was performed in all patients using 3.0 tesla MR scanners . The standardized neuroimaging protocol included T1-weighted imaging , T2-weighted imaging , fluid-attenuated inversion recovery and susceptibility weighted imaging . MR scanning parameters: T1WI: repetition time /echo time = 1,909/20.2 milliseconds , slice thickness = 5 mm T2WI: TR/TE = 5,000/125 ms, slice thickness = 5 mm FLAIR: TR/TE = 8,502/159.4 ms, slice thickness = 5 mm and SWI: TR/TE = 78.6/47.6 ms, slice thickness = 2 mm.
On the 4-point CSVD burden scale, one point was allocated to each of the following MRI parameters: severe WMH , presence of one or more acunes of presumed vascular origin, one or more deep CMBs, and moderate to severe basal ganglia EPVS. Thus, the total CSVD burden score could range from 0 to 4 . Severe CSVD burden score was defined when score > 2.
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Target Trial Emulation In The Ehr From The Us Rpdr And Uk Cprd
We emulated the target trial in cohorts from the US RPDR and UK CPRD EHR databases with a one-year run-in period. Our target trial outcomes were time to first diagnosis of dementia or death in type II diabetics over age 50, starting on metformin- or sulfonylurea-monotherapy, and followed for at least one year. Of note, the one-year run-in period was selected to ensure sufficient drug exposure before measuring outcomes. While the duration of a clinical trial is usually fixed, the duration of follow-up in the emulated trial is often much longer UK CPRD median: 6.0 years ).
BMI=Body Mass Index eGFR=estimated Glomerular Filtration Rate HES=Hospital Episode Statistics ICD=International Classification of Diseases IPTW=Inverse Propensity score of Treatment Weighting MCI=Mild Cognitive Impairment ONS=Office for National Statistics PCP=Primary Care Physician.
SES and IMD are distinct, country-specific socioeconomic indicators, intended for comparison withinrather than acrossthe two cohorts. BMI=Body Mass Index COPD=Chronic Obstructive Pulmonary Disease CVD=Cardio-Vascular Disease HbA1C=glycosylated hemoglobin. IMD=Index of Multiple Deprivation . IMD, smoking status, HbA1C, and BMI had 7%, 2%, 21%, and 3% of missing values in the UK CPRD, respectively. The corresponding statistics presented in the table are valid percentages out of patients without missing information. **Stroke and CVD indicators were collapsed.
Metformin As An Antidiabetic Drug Strategy For Alzheimers Disease Treatment
3.1. Preclinical Animal Studies with Metformin
Table 1.Table 1.
|Neuroprotection, Enhanced memory, reduced inflammation, regulation of AMPK/mTOR/S6K/Bace1 pathway.|
|2||SAMP8 mouse model of random onset- AD/M||12 months old||Increased PKC, improved pGSK-3ser9,reduced pTau404 and APPc99, enhanced learning and memory.|
|3||350 mg/kg/d||Until 1416 months-old||increases insulin sensitivity in male, lifespan extension and delayed degradation of the estrous cycle in female|
|4||Stimulate AMPK, mediating the pleiotropy|
|5||50, 100200 mg/kg/d||3 weeks|
|6||Enhances neuronal activity and neuropathological modifications, prevent synaptic plasticity impairment|
|7||Modulation of glucose delivery and uptake, anti-neuroinflammatory function, maintenance of synaptic plasticity|
|8||Suppress glycemic levels and cognitive dysfunction, increases insulin receptor sensitivity, facilitate neuronal survival|
|9||4 mg/mL in drinking water||2 months||Promoted the phagocytosis of A and tau proteins by enhancing microglial autophagy capability|
3.2. Metformin in Clinical Studies
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Swedish Cause Of Death Register
The records in the Death Register begin from the year 1952 and are the basis for official statistics on causes of death in Sweden . The registers purpose is to describe the development of national all-cause and specific-cause mortality.
We extracted the information from the Death Register since its initiation until October 16, 2018the end of the study follow-up. Overall mortality was considered if a valid record was present. The information on mortality was used to determine censoring and to account for patient dropout.
Association Of Metformin Use And Ad According To Depression
As depression is a risk factor or often precursor to AD, a higher prevalence of depression in the case population may act as a confounding factor in assessing the risk of AD in metformin users. Therefore, we performed subgroup analyses in prespecified strata of clinical interest to assess effect modification. The association with AD in metformin users was prominent in patients with and without depression . Of note, the risk of AD associated with metformin use was substantially greater in people with depression , while the significance of this association was maintained in patients without depression . This suggests that the association between metformin and AD risk is independent of depression, although depression has an additive effect on AD risk.
Tips To Reduce Sugar In Your Diet
Sugar and sweeteners are added to many foods that we bake or buy in a box or can. When you stay aware of this fact it can be easier to lower your sugar intake. Eat a diet that is naturally low in sugar by following these steps:
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Blood Vessel Damage In Diabetes Leads To Brain Fog Memory Loss
Blood sugar highs and lows create problems with blood circulation. Restricted circulation to the brain starves it of nutrients and oxygen. The brain cant function at its peak when it lacks nourishment therefore, symptoms of brain fog begin.
Circulation problems arent the only effect diabetes has on blood vessels. Hyperglycemia damages vessel walls over time, reducing their flexibility and responsiveness to the blood flow within them. In the brain, blood vessels need to flex to accommodate changing circulation. The brain adjusts the amount of blood it uses to support the functioning of various areas and structures. When blood vessels are rigid, they dont move fluidly to supply nutrients and oxygen where theyre most needed. As a result, memory loss, reasoning, processing speed, and more are compromised .
Diabetes and brain fog make life difficult. Is there a fix?
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Metformin Causes Scary Lactic Acidosis
The risk of metformin causing lactic acidosis of the blood is exceedingly rare. A Cochrane systematic review of 70,490 patients with type 2 diabetes on metformin did not report a single case of metformin-induced lactic acidosis. The risk of metformin causing lactic acidosis appears to be no greater than that of non-metformin therapies.
Outcomes And Major Covariates
The primary clinical outcome was defined as the first diagnosis of the overall ND, including AD , PD , HD , dementia and mild cognitive impairment . The secondary clinical outcomes were separately measured by AD, PD, HD, dementia and cognitive impairment.
The length of metformin exposure was categorised into five levels by exposure years over the study period from the index date to the time the first clinical outcome happened, death or the end of data availability. These levels include
never had metformin treatment,
12 years ,
24 years and
> 4 years.
The length cut-off was determined by quartiles of the length of metformin exposure distribution. Further, a binary variable for metformin treatment represented patients who had any length of metformin treatment or never had metformin treatment. The metformin average daily dosage during the entire follow-up period was calculated by metformin dosage and total prescription/refill date.
The agents in use for treatment of T2DM were identified at baseline and classified as insulin secretagogues , agents that may increase insulin sensitivity agonists, dipeptidyl peptidase 4 inhibitors, amylin analogue and thiazolidinediones) and others . Antihypertension medications include beta-blockers, ACE inhibitors, angiotensin II receptor blockers, calcium channel blockers and diuretics. Medications to treat hyperlipidaemia include statins, niacin, bile acid resins, fibric acid derivatives and cholesterol absorption inhibitors.
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Metformin And Dementia What You Need To Know
Many tend to wonder how metformin and dementia are related. Metformin is a popular prescription that helps treat Type ll diabetes. It helps decrease the amount of sugar that is present in your blood. Ever since it has hit the market, there have been many myths about metformin and dementia being connected. Today, we will take a glimpse at the link between metformin and dementia and whether there is even a connection between the two.
What exactly is dementia?
Dementia is described as illnesses and diseases that relate to memory loss and challenges with thinking and speaking. A perfect example of dementia is Alzheimers. Alzheimers is a neurodegenerative disease and is the most common cause of dementia. In addition, it works by destroying the nerve cells in the brain. It may be a surprise, but another well-known condition that can cause incident dementia is Parkinsons disease.
Wait, so is there a link between metformin and dementia?
In short, yes. Many studies have shown that metformin does not cause dementia. In fact, they show that it can help lower the risk of getting dementia.
However, many studies have shown a link between diabetic and other insulin sensitizer metformin users and the occurrence of dementia. Many studies even show an increased risk of developing dementia when using metformin.
Unfortunately, current research between the link of metformin and dementia is not clear. Many more clinical trials and observations are needed before we get a set in stone answer.
The Link Between Increased Statin Use And The Dementia Epidemic
As noted by the organization Be Brain Fit , there has been a massive increase in the number of Americans taking statin drugs like Crestor and Lipitor in recent years. At the same time, there has been an astronomical increase in the number of people experiencing memory loss, dementia and Alzheimers disease, which is now the sixth leading cause of death in the United States. BBF suggests that these two statistics may be no coincidence.
People are generally only told about the link between cholesterol and heart disease, but cholesterol also has incredibly important functions in the body. It is found in particularly high concentrations in the brain, with more than 60 percent of this important organ consisting of fat. The brain uses cholesterol to manufacture neurotransmitters, the chemicals which enable brain cells to communicate with each other. Neurotransmitters are also responsible for regulating mood, as well as facilitating focus and the ability to remember things, learn new things and cope with stress.
When normal neurotransmitter activity is disrupted, psychiatric disorders and nervous system diseases can be triggered.
For this reason, doctors admit that high cholesterol levels help prevent dementia in the elderly but will not admit the inverse: that low cholesterol levels can be linked to an increased risk of Alzheimers and other forms of dementia.
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Diabetes In Middle Age May Cause Memory Problems
Study also found that high blood pressure has similar impact
WEDNESDAY, March 19, 2014 People who develop type 2 diabetes or high blood pressure in middle age appear more likely to suffer brain damage that can contribute to dementia as they grow older, a new study finds.
Diabetes might actually shrink the brain over a long period of time, reducing the size of crucial areas like the hippocampus, which plays an important role in short- and long-term memory, according to the study.
People who had diabetes earlier in life had much worse brain than those who had it later in life, said lead author Dr. Rosebud Roberts, a Mayo Clinic researcher. These scans are showing us that cognitive impairment happens over a long period of time. The earlier you develop type 2 diabetes, the more likely you are to have damage.
Diabetes has long been linked to problems with thinking and memory later in life, but this study is the first to provide solid evidence explaining why that occurs, said Keith Fargo, director of scientific programs and outreach for the Alzheimers Association.
The study participants then underwent MRI brain scans to look for signs of brain damage that can be an early indication of dementia.
Can Anything Help Diabetes Brain Fog And Memory Loss
So far, there isnt a cure for diabetes, nor is there a known way to end brain fog and memory loss that diabetes can cause. However, there are things you can do to improve your blood sugar and minimize the effects of brain fog.
Lifestyle changes are key to improving blood sugar control.
- Increase physical activity, exercising almost every day for at least 30 minutes
- Reduce processed foods, including sugar
- Increase healthy foods
- Drink water to hydrate your brain
- Sleep seven- to eight hours per night
Sometimes, lifestyle changes dont do quite enough to repair brain damage and reduce brain fog and memory loss. Researchers are working on developing a medication that will repair blood vessels. Such medication is still in the future, however, so being vigilant about healthy lifestyle choices is essential. Diabetes and brain fog and diabetes and memory loss dont have to interfere in the quality of your life.
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You Cant Have A Ct Scan With Contrast When Taking Metformin
Intravenous contrast is often given prior to CT scan imaging. In patients with no evidence of acute kidney injury or end-stage kidney disease, theres no need to discontinue metformin either prior to or following the administration of contrast media. In patients taking metformin who have acute kidney injury or severe chronic kidney disease , metformin should be temporarily discontinued prior to the procedure and withheld for 48 hours after the procedure.
How Can Diabetes Affect Memory Loss
Memory loss in diabetes can be a short term problem brought on by too low or high blood glucose levels.
During hypoglycemia , for example, you may struggle to remember words. This is not necessarily a sign of a long term problem. In most cases, raising sugar levels over 4 mmol/l should get your memory back to normal.
If memory problems happen at other times and this significantly affects your life, speak to your GP.
Diabetes can increase the risk of developing long-term memory problems if blood glucose levels are less well controlled. High blood glucose levels , over a number of years, can damage the nerves, including those of the brain, which can increase the risk of dementia
Research shows that good diabetes management can help prevent memory problems from developing or advancing.
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