Data Extraction And Quality Assessment
We extracted the following variables from each study: name of the first author publication year country follow-up time in years study resource definition of MCI genders of patients mean age of patients baseline mini-mental state examination score number of patients at the baseline and the proportion of completing the follow-up overall incidence of dementia or AD exposure assessment and effect size and 95% CIs. The discrepancies were resolved by discussion. If studies did not report RR, HR or OR, the raw data were reviewed to determine whether effect size could be calculated. In studies that reported both crude RRs and adjusted RRs, the adjusted figures were used.
The Newcastle Ottawa Scale was used to assess the quality of each study. This measure assesses aspects of methodology in observational studies related to study quality, including selection of cases, comparability of populations and ascertainment of exposure to risks. We identify high quality choices with a star. A study can be awarded a maximum of one star for each numbered item within the Selection and Exposure categories. A maximum of two stars can be given for Comparability. Studies with a score equal to or higher than seven were considered to be high quality.
What Causes Mild Cognitive Impairment
Many factors can cause problems with memory and thinking. There is no single cause of MCI, and it’s more likely to occur as someone ages. Estimates vary, but roughly 10% to 20% of people over age 65 have MCI, with the risk increasing as someone gets older. Other factors like genetics and certain conditions including diabetes, depression, and stroke may affect a persons risk for MCI.
In some cases, memory and thinking problems may be caused by conditions that are treatable. For example, a bad reaction to medication, emotional problems, drinking too much alcohol, blood clots or tumors in the brain, or a head injury can all cause serious memory problems that can be resolved with treatment.
Mri Acquisition And Brain Segmentation
Acquisition of 1.5 T MRI and 3.0 T MRI data at each of the multiple ADNI sites followed a described standardized protocol developed by ADNI. See for sequence details.
The MRI images from ADNI were originally processed with two different versions of FreeSurfer and made available through the ADNI database. In previous work we have shown that the use of different versions of FresSurfer may lead to a relatively large discrepancy in the atrophy estimations. We therefore re-processed all the included MRI images using the same version of FreeSurfer , using the longitudinal stream of FreeSurfer. In the longitudinal stream, an unbiased within-subject template space and image is created using robust, inverse consistent registration. Several processing steps, such as skull stripping, Talairach transforms, atlas registration as well as spherical surface maps and parcellations are then initialized with common information from the within-subject template, significantly increasing reliability and statistical power.
A measure of the total hippocampus volume was derived by combining the volume of the left and right hippocampi. To reduce the effect of individual and gender differences in brain sizes, the volumes were normalized using the total intracranial volume measure estimated by FreeSurfer.
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Memory Loss Has Long Been Accepted As A Normal Part Of Ageing
Recently there has been increasing recognition that some people experience a level of memory loss greater than that usually experienced with ageing, but without other signs of dementia. This has been termed Mild Cognitive Impairment . As MCI has only recently been defined, there is limited research on it and there is much that we do not yet understand.
Mild Cognitive Impairment Vs Normal Aging
Normal aging and mild cognitive impairment are definitely distinct from one another, Dr. Fredericks says.
Basically, mild cognitive impairment is when someone has clear symptoms showing changes in their memory or their thinking, but the changes dont affect their ability to do their day-to-day activities, she says. That is what distinguishes it from dementia.
People come to me and ask, Should I do Sudoku or crossword puzzles? I tell them to do anything that they find enjoyable and cognitively challenging.Carolyn Fredericks, MD, Yale Medicine neurologist
With MCI, the changes are often noticed by friends and family members, too. Its also something that can be seen on a neuropsychological evaluation, which measures how well your brain is working by testing reading, language usage, learning, processing speed, reasoning, and problem-solving, as well as mood and personality.
Much of what differentiates MCI from normal aging has to do with how often someone struggles with memory or cognition.
Its common for any of us to end up in our kitchen with no idea why we are there or to run into someone in the grocery store and forget their name. But when it starts to happen repetitively and on a day-to-day basis, thats when you start to worry about it, Dr. Fredericks says.
What, then, is normal aging? Do memory and cognition naturally decline in everyone as we age? Like many of the great questions of the brain, there isnt a clear answer, Dr. Fredericks says.
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Whats The Difference Between Mild Cognitive Impairment And Decline Due To Normal Aging
Some gradual mental decline is seen with normal aging. For example, the ability to learn new information may be reduced, mental processing slows, speed of performance slows, and ability to become distracted increases. However, these declines due to normal aging do not affect overall functioning or ability to perform activities of daily living. Normal aging does not affect recognition, intelligence, or long-term memory.
In normal aging, a person may occasionally forget names and words and misplace things. With mild cognitive impairment, the person frequently forgets conversations and information that one would ordinarily remember such as appointments and other planned events.
Construction Of The Prognosis Prediction Model
All data were strictly separated into a discovery cohort and a validation cohort. To generate datasets of pre-selected SNPs, we used two thirds of the entire discovery cohort to calculate P values in each cross-validation step. The P values corresponding to the SNPs were calculated with the following logistic regression model between MCI-C and MCI-NC:
where XSNP is the SNP genotypes and is the respective coefficients. The logistic regression was implemented using PLINK . From p pre-selected SNPs , we focused on SNP-miRNA pairs with eQTL effects . The SNP-miRNA pairs with adjusted P value < 0.1 were obtained from an in-house miR-eQTL database . Using a combination of the miR-eQTLs and clinical factors , a prognosis prediction model was constructed based on a Cox proportional hazard model using two thirds of the discovery cohort as defined by:
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What Are The Symptoms Of Mild Cognitive Impairment
The symptoms of MCI are not as severe as the symptoms of Alzheimer’s disease or dementia. For example, people with MCI do not experience the personality changes or other problems that are characteristic of Alzheimer’s. People with MCI are still able to take care of themselves and do their normal daily activities.
Signs of MCI may include:
- Losing things often
- Forgetting to go to events or appointments
- Having more trouble coming up with words than other people of the same age
Movement difficulties and problems with the sense of smell have also been linked to MCI.
Prediction Models For Conversion From Mild Cognitive Impairment To Alzheimers Disease: A Systematic Review And Meta
- 1Evidence-Based Nursing, School of Nursing, Lanzhou University, Lanzhou, China
- 2Department of Neurology, Second Hospital of Lanzhou University, Lanzhou, China
- 3Department of Nursing, Gansu Provincial Hospital, Lanzhou, China
- 4First School of Clinical Medicine, Lanzhou University, Lanzhou, China
Background and Purpose: Alzheimers disease is a devastating neurodegenerative disorder with no cure, and available treatments are only able to postpone the progression of the disease. Mild cognitive impairment is considered to be a transitional stage preceding AD. Therefore, prediction models for conversion from MCI to AD are desperately required. These will allow early treatment of patients with MCI before they develop AD. This study performed a systematic review and meta-analysis to summarize the reported risk prediction models and identify the most prevalent factors for conversion from MCI to AD.
Methods: We systematically reviewed the studies from the databases of PubMed, CINAHL Plus, Web of Science, Embase, and Cochrane Library, which were searched through September 2021. Two reviewers independently identified eligible articles and extracted the data. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies checklist for the risk of bias assessment.
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Preventing More Cognitive Decline
If you are diagnosed with MCI, is there anything you can do to prevent further cognitive decline? While there is no specific treatment for MCI, there is evidence that following a healthy diet, for anyone, can help, Dr. Fredericks says.
Specifically, Dr. Fredericks points to research about the so-called Mediterranean diet, which emphasizes whole grains, seafood, and nuts, and the DASH diet, which is designed to help lower or control high blood pressure.
Either of these or a combination of the two can be effective in slowing cognitive decline, Dr. Fredericks says. Also, as we get older, theres good evidence that moderate-intensity cardiovascular exercise for 30 minutes, five times a week helps. We all should be doing this, especially those of us with a family history of dementia.
Furthermore, staying cognitively activeespecially after retirementis key, she adds. People come to me and ask, Should I do Sudoku or crossword puzzles? I tell them to do anything that they find enjoyable and cognitively challenging. It has to be enjoyable or you likely won’t do it, she says. But it also has to really stretch you.
Research Suggests That People With Mild Cognitive Impairment May Be Helped But The Findings Are Far From Conclusive
An earlier version of this story incorrectly said the study was published in the New England Journal of Medicine. It was published in NEJM Evidence, a medical journal from the NEJM Group. This version has been corrected.
For years, scientists have been trying to figure out whether brain workouts such as puzzles and online cognitive games could strengthen our minds and slow the process of aging.
Now, a study published in NEJM Evidence has found that regularly attempting a crossword may help slow decline in some people with mild cognitive impairment, an early stage of faltering memory that can sometimes progress to dementia.
While the study didnt investigate whether crosswords benefit younger adults who are not dealing with cognitive decline, it suggests that keeping your mind active as you age may benefit your brain. And the research offers hope to those diagnosed with mild cognitive impairment that they may be able to stave off further declines in the memory, language problems and decision-making that are the hallmark of the condition.
The American Academy of Neurology estimates that mild cognitive impairment affects about 8 percent of people ages 65 to 69 10 percent of people ages 70 to 74 15 percent of people ages 75 to 79 25 percent of those ages 80 to 84 and about 37 percent of people 85 and older.
Richard Sima will return next week.
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Can We Identify The People Who Will Go On To Develop Dementia
A lot of research has focused on trying to identify which people with MCI will go on to develop dementia. If this could be predicted, it would mean people could be offered a range of support earlier in the development of dementia. In the future, for example, researchers might develop drugs to prevent the progression of MCI to dementia.
Most research that looks at predicting which people with MCI will go on to develop dementia has focused on Alzheimer’s disease. This is because it is the most common cause of dementia and also the best understood. There is good evidence that simple tests, based on learning lists of words, do a fairly good job of predicting those who will develop Alzheimer’s.
Researchers have also tried to identify which people with MCI will go on to develop dementia due to Alzheimer’s disease by using brain scans. These scans help to detect changes in brain structure and function.
A different approach to this problem is to measure the amount of certain proteins in the fluid that circulates around the brain and spinal cord. These proteins – called amyloid and tau – are analysed because they may indicate that the changes in the brain that take place in Alzheimer’s disease are already underway.
While these are all promising areas of research, it is not yet possible to predict with certainty whether a person with MCI will develop Alzheimer’s disease. Even a combination of memory tests, scans and protein level measurements cannot give a definite answer.
Characteristics Of Eligible Studies
A total of 18 studies were included in this study. Notably, 12 of the studies data were conducted using the data from the ADNI dataset. Of the 18 studies we included, 14 were retrospective cohort studies and four were prospective cohort studies. Among the diagnostic criteria for predicting the outcome of AD, five studies used NINCDS-ADRDA diagnostic criteria, while other studies used other criteria, such as Diagnostic and Statistical Manual of Mental Disorders , Mini-Mental State Examination , Alzheimers Disease Assessment Scale cognitive scale, and Clinical diagnostic assessments. Shigemizus study uses the National Institute on Aging-Alzheimers Association workgroups on diagnostic guidelines for AD as the diagnosis of outcome indicators. The follow-up duration of the studies ranged from 0.5 to 7 years, and the dementia conversion rate of elderly patients with MCI ranged from 14.49 to 87%. The basic characteristics of the included studies are shown in Table 1.
Table 1. Primary characteristics of the prediction model included in the review .
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Can Mci Be Treated
Currently, there is no specific treatment for MCI. A number of studies are investigating different treatments, such as the cholinesterase inhibitors used to treat Alzheimers disease, Ebixa, nonsteroidal anti-inflammatory drugs , Vitamin E and statins . At this stage no drug therapy for MCI has proven effective, but work continues. As new medical treatments for Alzheimers disease arise, it is likely they will also be tested in people with MCI. Studies involving drug trials have shown preliminary evidence that drug treatments can effectively delay the progression to dementia.
Cognitive training has been suggested as useful for MCI and it is important to maintain a healthy diet, have regular physical exercise, and maintain good general health particularly controlling blood pressure, lowering cholesterol levels, and stopping smoking.
In most cases, a person diagnosed with MCI will not undergo any medical treatment but will be regularly monitored for changes in their memory. Counselling may assist people with MCI to find ways to adjust to the changes they are experiencing and to learn about ways to compensate for their memory difficulties.
Cognitive Status At Follow
We defined cognitive status at follow-up using NACC UDS clinician diagnosis at baseline and after 3 years of follow-up. We adopted a conservative definition of reversion to NC, namely a clinician diagnosis of NC after 3 years of follow-up, whereas Impaired-Not-MCI was retained with MCI as stable MCI. Progression to dementia was defined as a clinician diagnosis of dementia.
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Nature Of Cognitive Impairment
Cognitive functioning is typically characterized into one of 5 domains: 1) learning and memory, 2) language, 3) visuo-spatial, 4) executive and 5) psychomotor. These domains have a rough correspondence with their cerebral localization. For a diagnosis of MCI, only one of these areas must be impaired in order to make a diagnosis, whereas more than one domain must be impaired to make a diagnosis of dementia. Evidence for involvement of individual domains can be obtained from the history, a brief mental status examination or neuropsychological testing.
Non-amnestic cognitive impairments are nearly as common as the amnestic forms. Non-amnestic impairment can involve word finding and speech difficulties, impaired geographic orientation, visual perception problems and impaired mental agility. When there is dysfunction in more than one cognitive domain in persons with MCI, referred to as multidomain MCI, the risk for decline to dementia is much higher than when there are isolated memory problems or word finding problems8, 14.
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Can Mild Cognitive Impairment Be Reversed
In some cases, MCI may be reversible.
There arent currently any medications that have been approved by the Food and Drug Administration to treat MCI.
But MCI can be treated if its caused by any of the following:
- stroke or vascular disease
- traumatic brain injury like a concussion
- a medication, as a side effect
- depression or anxiety
Changing or stopping medications or working with a therapist or doctor to treat insomnia, depression, or anxiety could reverse or even cure MCI.
In other cases, MCI will advance to dementia or Alzheimers disease, which are progressive conditions. This means that your ability to perform daily activities may worsen over time.
Diffusion Mri Preprocessing And Gbss Analysis
Diffusion images were preprocessed using FMRIB Software Library , including the brain extraction and the correction of eddy current distortion and inter-volume head motion. After the data preprocessing, the resulting diffusion data were fitted to the NODDI model using the NODDI MatLab Toolbox to generate NDI maps, ODI maps, and fiso maps. The tensor metric fractional anisotropy was estimated with b=1000 images by fitting using FSLs DTIFIT tool. Then, All the NODDI parameter maps and FA maps were resampled to 2×2×2mm to improve the resolution.
Fig. 4: Processing steps of GBSS.
a GM fraction maps were generated by subtracting the WM fraction and the CSF fraction from one. The GM, WM, and CSF fraction were used to generate pseudo T1-weighted images. b Pseudo T1-weighted images from all subjects were registered to the OASIS-30_Atropos_template and all resampled NODDI maps and GM fraction maps were aligned to the template. c GM fraction images from all subjects were averaged to generate mean GM images, which were skeletonized using FSLs tbss_skeleton tool. All NODDI parameters maps and GM fraction maps were projected onto this GM skeleton. GBSS gray matter-based spatial statistics, GM gray matter, WM white matter, FA fractional anisotropy, CSF cerebrospinal fluid, NODDI Neurite Orientation Dispersion and Density Imaging, NDI neurite density index, ODI orientation dispersion index, fiso volume fraction of isotropic diffusion, FSL FMRIB Software Library.
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