Alzheimer's & other dementias
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A three-year study involving 169 people with MCI has found that those who later developed Alzheimer's disease showed 10-30% greater atrophy in two specific locations within the hippocampus, the cornu ammonis (CA1) and the subiculum. A second study comparing the brains of 10 cognitively normal elderly people and seven who were diagnosed with MCI between two and three years after their initial brain scan and with Alzheimer's some seven years after the initial scan, has confirmed the same pattern of hippocampal atrophy, from the CA1 to the subiculum, and then other regions of the hippocampus.
Apostolova, L. G., Thompson, P. M., Green, A. E., Hwang, K. S., Zoumalan, C., Jr, C. R. J., Harvey, D. J., et al. (2010). 3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI. Human Brain Mapping, 9999(9999), NA. doi:10.1002/hbm.20905
Apostolova, L.G. et al. In press. Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal. Neurobiology of Aging, Available online 24 September 2008.
A study involving 117 healthy elderly (aged 60-91) has found that, while increasing age was associated with poorer memory for names of famous people, age didn’t affect memory for biographical details about them. It also found that names served as better cues to those details than faces did. A follow-up study (to be published in Neuropsychologia) found that, in contrast, those with mild cognitive impairment and early Alzheimer’s showed not only an increased inability to remember names, but also a decline in memory for biographical details.
Langlois, R. et al. 2009. Manque du nom propre et effet de la modalité sur la capacité à reconnaître des personnes connues au cours du vieillissement normal. Canadian Journal on Aging/ La Revue canadienne du vieillissement, 28 (4), 337-345.
A study involving 176 patients with Alzheimer's, vascular dementia or mixed dementia, or mild cognitive impairment, has found that 82% of the patients with changes in their white matter were apathetic, compared to an overall rate of 58%. This discovery suggests that there is a common biological reason behind this apathy, irrespective of which type of dementia a patient has. White matter changes were also associated with age, gender, blood pressure, hypertension, ischaemic heart disease, mental slowness, disinhibition, gait disturbance and focal neurologic symptoms. Apathy, mental slowness and age were the most consistent predicting factors for WMCs.
Jonsson, M., Edman, Å., Lind, K., Rolstad, S., Sjögren, M., & Wallin, A. (2009). Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia. International Journal of Geriatric Psychiatry, 9999(9999), n/a. doi: 10.1002/gps.2379.
A study involving 111 older adults with mild cognitive impairment, of whom 28 progressed from mild cognitive impairment to dementia over the next 2 ½ years, found only one factor predicted conversion from mild cognitive impairment to dementia: the degree of functional impairment (ability to perform routine activities) at the beginning of the study. Other cognitive and neurological variables were not predictive.
Farias, S.T. et al. 2009. Progression of Mild Cognitive Impairment to Dementia in Clinic- vs Community-Based Cohorts. Archives of Neurology, 66(9), 1151-1157.
A study involving 76 older people with no memory problems and 87 older people with amnestic mild cognitive impairment has found that those (25 of the 87) who had developed Alzheimer’s a year later were significantly worse at a money management task. Compared to those with no memory problems, as well as those with MCI who did not develop dementia, those who did develop Alzheimer’s not only dropped 9% on checkbook management abilities and 6% on overall financial knowledge and skills, but also performed more poorly at the beginning of the study. The task included counting coins, making grocery purchases, understanding and using a checkbook, understanding and using a bank statement, preparing bills for mailing, and detecting fraud situations.
Triebel, K.L. et al. 2009. Declining financial capacity in mild cognitive impairment: A 1-year longitudinal study. Neurology, 73, 928-934.
A study involving 679 seniors (65+) has found that those with small areas of brain damage called white matter hyperintensities, often referred to as ministrokes, were nearly twice as likely to have mild cognitive impairment that included memory loss (amnestic MCI), while those who had infarcts (areas of dead tissue usually called strokes) were more likely to experience mild cognitive impairment in abilities other than memory loss (non-amnestic MCI). In other words, ministrokes predicted memory problems, while strokes predicted non-memory problems.
Luchsinger, J.A. et al. 2009. Subclinical cerebrovascular disease in mild cognitive impairment. Neurology, 73, 450-456.
In a study in which 49 seniors (65+) were followed for an average of 9.5 years, of whom 24 developed mild cognitive impairment, those with the fastest rate of growth in white matter lesions were more likely to develop mild cognitive impairment than those with a slow rate of growth. The amount of lesions in healthy brains at the start of the study was not a factor; the crucial factor was the rate of progression.
Silbert, L.C. et al. 2009. Cognitive impairment risk: White matter hyperintensity progression matters. Neurology, 73, 120-125.
A study involving 269 patients with mild cognitive impairment provides evidence that a fully automated procedure called Volumetric MRI (that can be done in a clinical setting) can accurately and quickly measure parts of the medial temporal lobe and compare them to expected size. It also found that not only atrophy in the hippocampus but also the amygdala is associated with a greater risk of conversion to Alzheimer’s.
Kovacevic, S. et al. 2009. High-throughput, Fully Automated Volumetry for Prediction of MMSE and CDR Decline in Mild Cognitive Impairment. Alzheimer Disease & Associated Disorders, 23 (2), 139-145.
A study involving 60 patients with subjective cognitive impairment, 37 patients with non-amnestic mild cognitive impairment, and 71 with amnestic mild cognitive impairment, has found that 52% of those with SCI, 68% of those with naMCI, and 79% of those with aMCI showed decreased concentrations of Aβ42 and increased concentrations of tau protein in the cerebrospinal fluid. The findings confirm the use of biomarkers in the CSF for very early diagnosis.
Visser, P.J. et al. 2009. Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment and mild cognitive impairment in the DESCRIPA study: a prospective, case-control study. The Lancet Neurology, 8 (7), 619–627.
A new cognitive test for detecting Alzheimer's has been developed, and designed to be suitable for non-specialist use. The TYM ("test your memory") involves 10 tasks including ability to copy a sentence, semantic knowledge, calculation, verbal fluency and recall ability. It has been tested on 540 healthy individuals and139 patients with diagnosed Alzheimer's or mild cognitive impairment. Healthy controls completed the test in an average time of five minutes and gained an average score of 47 out of 50, compared to 45 for those with mild cognitive impairment, 39 for those with non-Alzheimer dementias and 33 for those with Alzheimer’s. Among controls, the average score was not affected by age until after 70, when it showed a small decline. There were no gender or geographical background differences in performance. The TYM detected 93% of patients with Alzheimer's, compared to only 52% by the widely used mini-mental state examination.
Brown, J. et al. 2009. Self administered cognitive screening test (TYM) for detection of Alzheimer’s disease: cross sectional study. BMJ, 338:b2030, doi: 10.1136/bmj.b2030 Full text available here.
A test first developed for use with nonhuman primates is now being used to detect mild cognitive impairment (MCI) in humans. The infrared eye-tracking test involves showing one image and then another after a 2-second delay, and then repeating the test 2 minutes later. Those without cognitive impairment spend most of their time looking at the new image, but it was found that those with MCI spent less time looking at the new picture, presumably because they have less memory of seeing the original image before. Those with Alzheimer's disease look at both images equally. It’s hoped that this test may allow dementia to be spotted much earlier.
Crutcher, M.D. et al. 2009. Eye Tracking During a Visual Paired Comparison Task as a Predictor of Early Dementia. American Journal of Alzheimer's Disease and Other Dementias, Published online February 26 2009.
Cerebrospinal fluid samples from 410 volunteers (100 with mild Alzheimer’s; 196 with MCI; 114 cognitively normal older adults) has revealed that concentrations of amyloid beta-42 peptide and tau protein successfully assessed brain status and predicted development. The test diagnosed Alzheimer’s with 96% accuracy; ruled out Alzheimer’s with 95% accuracy; and predicted the conversion from MCI to Alzheimer’s with 82% accuracy.
Shaw, L.M. et al. 2009. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Annals of Neurology, Published Online March 18 2009.
Data from 41 studies has revealed the risk of those with mild cognitive impairment developing dementia is much less than thought. MCI is found in about 1 in 6 people seen in general practice, and it was thought that the risk of developing dementia was up to 15% per year, making deterioration almost inevitable within 5 to 10 years. It now appears that the risk is 10% per year in high risk groups (9.6% for dementia overall; 8% for Alzheimers; 2% for vascular dementia) and only 5% per year in low risk groups (5% for dementia overall; 7% for Alzheimers; 1.6% for vascular dementia). More importantly, only 20-40% developed dementia even after 10 years and the risk appeared to reduce slightly with time.
Mitchell, A.J. & Shiri-Feshki, M. 2009. Rate of progression of mild cognitive impairment to dementia – meta-analysis of 41 robust inception cohort studies. Acta Psychiatrica Scandinavica, 119 (4), 252-265.
A study of 84 patients with mild Alzheimer's, 175 patients with MCI and 139 healthy controls has revealed a pattern of regional brain atrophy in patients with MCI that indicates a greater likelihood of progression to Alzheimer's. Brain scans results showed widespread cortical atrophy in some patients with MCI, most importantly, atrophy in parts of the medial and lateral temporal lobes and in the frontal lobes — a pattern also present in the patients with mild Alzheimer's disease. Those exhibiting such atrophy declined significantly over a year and were more likely to progress to a probable diagnosis of Alzheimer's. MCI patients without that pattern of atrophy remained stable after a year. It should be noted that such atrophy affects not only memory, but also planning, organization, problem solving and language.
McEvoy, L.K. et al. 2009. Alzheimer Disease: Quantitative Structural Neuroimaging for Detection and Prediction of Clinical and Structural Changes in Mild Cognitive Impairment. Radiology, Published online February 6.
A new chemical marker called FDDNP, which binds to plaque and tangle deposits in the brain, has enabled PET scans to reveal exactly where these abnormal protein deposits are accumulating, and has found that older age correlated with higher concentrations of FDDNP in the medial and lateral temporal regions of the brain, areas involved with memory, where plaques and tangles usually collect. Of the 76 study volunteers, 34 carried the ‘Alzheimer’s gene’. This group demonstrated higher FDDNP levels in the frontal region of the brain than those without the gene variant. Thirty-six of the volunteers had mild cognitive impairment, and these had higher measures of FDDNP in the medial temporal brain regions than normal volunteers. Those who had both MCI and the APOE-4 gene also had higher concentrations of FDDNP in the medial temporal brain regions than those who had MCI but not APOE-4. The pilot study offers hope of early diagnosis of brain impairment, before symptoms show themselves.
Small, G.W. et al. 2009. Influence of Cognitive Status, Age, and APOE-4 Genetic Risk on Brain FDDNP Positron-Emission Tomography Imaging in Persons Without Dementia. Archives of General Psychiatry, 66(1), 81-87.
A study of 503 seniors (aged 50-85) with no dementia found that 453 of them (90%) reported having occasional memory problems such as having trouble thinking of the right word or forgetting things that happened in the last day or two, or thinking problems such as having trouble concentrating or thinking more slowly than they used to. Such problems have been attributed to white matter lesions, which are very common in older adults, but all of the participants in the study had white matter lesions in their brains, and the amount of lesions was not tied to occasional memory problems. However it was found that those who reported having such problems had a smaller hippocampus than those who had no cognitive problems. This was most noteworthy in subjects with good objective cognitive performance.
van Norden, A.G.W. et al. 2008. Subjective cognitive failures and hippocampal volume in elderly with white matter lesions. Neurology, 71, 1152-1159.
An Australian study involving 138 older adults (50 years and over) with mild cognitive impairment, has found that those who undertook to achieve 2 ½ hours of physical activity each week (three 50 minute sessions), ranging from walking, ballroom dancing to swimming, for a six month period, continually out-scored the control group on cognitive tests during the 18 month testing period — showing that memory improvement was still evident a year after the supervised exercise period.
Lautenschlager, N.T. et al. 2008. Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease: A Randomized Trial. Journal of the American Medical Association, 300(9), 1027-1037.
A new, carefully validated questionnaire called Everyday Cognition (ECog) has been developed by seven psychologists. The 39-question screening tool is designed to enable mild functional problems in older adults to be quickly and easily identified. The questionnaire needs to be filled out by someone who knows an older adult well, such as a spouse, adult child, or close friend. It looks at everyday function in seven key cognitive domains: memory, language, semantic (factual) knowledge, visuospatial abilities, planning, organization and divided attention. The test has been shown to be sensitive to early changes present in Mild Cognitive Impairment, and unlike other cognitive tests, does not appear to be strongly influenced by education level. The test even differentiated between people diagnosed with mild impairment in memory only and those mildly impaired in several areas.
Farias, S.T. et al. 2008. The Measurement of Everyday Cognition (ECog): Scale Development and Psychometric Properties. Neuropsychology, 22 ( 4), 531-544.
A study involving over 2000 people between 70 and 89 years old, found 15% had mild cognitive impairment, and men were one-and-a-half times more likely to have MCI than women.
The research was presented at the American Academy of Neurology Annual Meeting in Chicago, April 12–19.
A study of nearly 1000 older adults (average age 76.3) without mild cognitive impairment at the start of the study found that over the follow-up period (average: 4.7 years), 334 individuals developed mild cognitive impairment, of which 160 were amnestic (reduced memory) and 174 were non-amnestic. Hypertension (high blood pressure) was associated with an increased risk of non-amnestic mild cognitive impairment; but not with amnestic mild cognitive impairment.
Reitz, C. et al. 2007. Hypertension and the Risk of Mild Cognitive Impairment. Archives of Neurology, 64(12), 1734-1740.
Older adults who have difficulty identifying common odors may have a greater risk of developing mild cognitive impairment, increasingly recognized as a precursor to Alzheimer’s disease. A study of nearly 600 older adults (average age 79.9) found that 30.1% developed mild cognitive impairment over the five-year period of the study. Risk of developing mild cognitive impairment was greater for those who scored worse on an odor identification test given at the start of the study. For example, those who scored below average (eight) were 50% more likely to develop MCI than those who scored above average (11). This association did not change when stroke, smoking habits or other factors that might influence smell or cognitive ability were considered. Impaired odor identification was also associated with lower cognitive scores at the beginning of the study and with a more rapid decline in episodic memory (memory of past experiences), semantic memory (memory of words and symbols) and perceptual speed. The odor test involved identifying 12 familiar odors given four possible alternatives to choose from.
Wilson, R.S., Schneider, J.A., Arnold, S.E., Tang, Y., Boyle, P.A. & Bennett, D.A. 2007. Olfactory Identification and Incidence of Mild Cognitive Impairment in Older Age. Archives of General Psychiatry, 64, 802-808.
A study involving 120 people over 60 found those who complained of significant memory problems who still performed normally on memory tests had a 3% reduction in gray matter density in their brains. This compares to 4% in those diagnosed with mild cognitive impairment. This suggests that significant memory loss complaints may indicate a very early "pre-MCI" stage of dementia for some people.
Saykin, A.J. et al. 2006. Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology, 67, 834-842.
A study of 20 older adults with mild cognitive impairment has found that the hippocampus was smaller in those who developed into Alzheimer's during the 3 year period.
Apostolova, L.G. et al. 2006. Conversion of Mild Cognitive Impairment to Alzheimer Disease Predicted by Hippocampal Atrophy Maps. Archives of Neurology, 63, 693-699.
Autopsies have revealed that the brains of patients with mild cognitive impairment display pathologic features that appear to place them at an intermediate stage between normal aging and Alzheimer's disease. For instance, the patients had begun developing neurofibrillary tangles, but the number of plaques was similar to that in healthy patients. All patients with mild cognitive impairment had abnormalities in their temporal lobes, which likely caused their cognitive difficulties, and many also had abnormalities in other areas that did not relate to the features of Alzheimer's disease. In a second study, of 34 patients with mild cognitive impairment who had progressed to clinical dementia before their deaths, 24 were diagnosed (post-mortem) with Alzheimer’s, and 10 with other types of dementia. As in the other study, all patients had abnormalities in their temporal lobes.
Petersen, R.C. et al. 2006. Neuropathologic Features of Amnestic Mild Cognitive Impairment. Archives of Neurology, 63, 665-672.
Jicha, G.A. et al. 2006. Neuropathologic Outcome of Mild Cognitive Impairment Following Progression to Clinical Dementia. Archives of Neurology, 63, 674-681.
A study of 3,957 people from the general population of Olmsted County, Minnesota is currently in train to find how many of those who did not have dementia might have mild cognitive impairment. A report on the findings so far suggests 9% of those aged 70 to 79 and nearly 18% of those 80 to 89 have MCI. Prevalence varied not only with age but also years of education: 25% in those with up to eight years of education, 14% in those with nine to 12 years, 9% in those with 13 to 16 years, and 8.5% in those with greater than 16 years.
Findings from this study were presented April 4 at the American Academy of Neurology meeting in San Diego.
Mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer's disease, has been categorized into two sub-types on the basis of differing symptoms. Those with the amnesic subtype (MCI-A) have memory impairments only, while those with the multiple cognitive domain subtype (MCI-MCD) have other types of mild impairments, such as in judgment or language, and mild or no memory loss. Both sub-types progress to Alzheimer's disease at the same rate. A new imaging technique has now revealed that these types do in fact have different pathologies. The hippocampus of patients with MCI-A was not significantly different from that of Alzheimer's patients (who show substantial shrinkage), but the hippocampus of those with MCI-MCD was not significantly different from that of the healthy controls.
Becker, J.T. et al. 2006. Three-dimensional Patterns of Hippocampal Atrophy in Mild Cognitive Impairment. Archives of Neurology, 63, 97-101.
A study involving retired National Football League players found that they had a 37% higher risk of Alzheimer's than other U.S. males of the same age. Some 60.8% of the retired players reported having sustained at least one concussion during their professional playing career, and 24% reported sustaining three or more concussions. Those with three or more concussions had a five-fold greater chance of having been diagnosed with mild cognitive impairment and a three-fold prevalence of reported significant memory problems compared to those players without a history of concussion. As the study was based on self-reported answers to the health questions, further studies are needed to confirm the findings, but it does seem likely that head injuries earlier in life increase the chance of developing dementia or mild cognitive impairment.
Guskiewicz, K.M., Marshall, S.W., Bailes, J., McCrea, M., Cantu, R.C., Randolph, C. & Jordan, B.D. 2005. Association between Recurrent Concussion and Late-Life Cognitive Impairment in Retired Professional Football Players. Neurosurgery, 57(4), 719-726.
Researchers have developed a brain scan-based computer program that quickly and accurately measures metabolic activity in the hippocampus, a key brain region that shrinks with the development of Alzheimer’s. The study followed 53 normal subjects aged 54 to 80 for at least 9 years and in some cases for as long as 24 years, and found that hippocampal glucose metabolism was significantly reduced on the first scan of those 25 individuals who would later experience cognitive decline related to either mild cognitive impairment or to Alzheimer's. The findings bring hope of being able to predict who will develop Alzheimer’s at least 9 years ahead of symptoms.
Mosconi, L., Tsui, W-H., De Santi, S., Li, J., Rusinek, H., Convit, A., Li, Y., Boppana, M. & de Leon, M.J. 2005. Reduced hippocampal metabolism in MCI and AD: Automated FDG-PET image analysis. Neurology, 64, 1860-1867.
A new study has found that rates of total brain volume loss may help identify patients with mild cognitive impairment who are at high risk of developing dementia. The study followed 55 people over 14 years, and found that loss of volume in the hippocampus predicted which mildly cognitively impaired individuals would stay stable and which would decline to Alzheimer's with 70% accuracy, while the rate of total brain volume loss was 62% accurate in predicting cognitive outcome. Combining both variables produced the strongest model: 75% accuracy. The discovery could help doctors plan early treatment strategies and prevention studies.
The study was presented at the 56th annual meeting of the American Academy of Neurology in San Francisco.
Early diagnosis of Alzheimer's is becoming more important with new medical and psychological interventions that can slow (but not stop) the course of the disease. Given this, it is suggested that more sensitive testing may be necessary for highly intelligent people, who, on average, show clinical signs of Alzheimer's later than the general population. Once they show such signs, they decline much faster. A study of 42 older people with IQ's of 120 or more, used two different test norms to forecast problems: the standard norm, derived from a large cross-section of the population, or an adjusted high-IQ norm that measured changes against the individual's higher ability level. The raised cutoffs predicted that 11 of the 42 individuals were at risk for future decline – compared with standard cutoffs, which indicated they were normal. True to the former prediction, three and a half years later, nine of those 11 people had declined. Six of those went on to develop mild cognitive impairment (MCI), a transitional illness from normal aging to a dementia (of which one type is Alzheimer's). Five of these individuals have since received a diagnosis of Alzheimer's disease, two years after this study was submitted. It is also suggested that, at the other end of the scale, those with below-average intelligence have the potential for being misdiagnosed as 'demented' when they are not, and the norms should be adjusted downwards accordingly.
Rentz, D.M., Huh, T.J., Faust, R.R., Budson, A.E., Scinto, L.F.M., Sperling, R.A. & Daffner, K.R. 2004. Use of IQ-Adjusted Norms to Predict Progressive Cognitive Decline in Highly Intelligent Older Individuals. Neuropsychology, 18 (1).
Researchers have developed a brief telephonic questionnaire that helps distinguish between persons with early signs of dementia and persons with normal cognitive function. The questionnaire provides a way to reach out to persons with dementia whose impairment otherwise may go undetected until substantial cognitive deterioration has occurred. The questionnaire consists of a test of delayed recall and 2 questions that ask whether the person needs help with remembering to take medications or with planning a trip for errands. It is estimated that of 100 people who score positive on this test, 42 will actually have cognitive impairment. In other words, this does not provide a diagnosis of Alzheimer’s, but provides evidence that further evaluation is required. The rate of false positives compares favorably to other types of screening tests. A further study is underway to confirm the validity and reliability of the test.
Fillit, H. et al. 2003. A Brief Telephonic Instrument to Screen for Cognitive Impairment in a Managed Care Population. Journal of Clinical Outcomes Management, , 419-429.
An analysis of data from 40 participants enrolled in a long-term study at the UCSD Alzheimer’s Disease Research Center (ADRC) found that "paper-and-pencil" cognitive skills tests administered to normal subjects averaging 75 years of age contained early signs of cognitive decline in those subjects who later developed Alzheimer’s disease. All participants were symptom-free when they took the test. The differences were quite subtle - only some performance measures were affected.
A three-year study of 48 healthy people from 60 to 80 years old, by New York University School of Medicine researchers, predicted which healthy elderly men and women would develop memory impairment based on scans of their brains. At the beginning of the study, everyone scored within the normal range on a battery of tests typically used to detect early loss of memory and other mental skills. However, PET scans revealed a reduction in glucose metabolism in an area of the brain called the entorhinal cortex among 12 people. Three years later, 11 of these people had experienced mild cognitive impairment and one had developed Alzheimer's disease. "Our work extends the use of PET scanning to identifying in normal aging subjects the earliest metabolic abnormalities that may lead to the memory losses referred to as mild cognitive impairment (MCI). The diagnosis of MCI carries a high risk for future Alzheimer's disease."
The study is published in the September 11 issue of The Proceedings of the National Academy of Sciences.
There are five healthy behaviors that appear to significantly reduce the risk of dementia,
A 35-year study that monitored the healthy behaviors of 2,235 Welsh men aged 45 to 59 at the beginning of the study has found that those who consistently followed at least four of these five healthy behaviors — regular exercise, no smoking, acceptable BMI, high fruit and vegetable intake, and low/moderate alcohol intake — experienced a 60% reduction in dementia and cognitive decline compared with people who followed none. They also had 70% fewer instances of diabetes, heart disease, and stroke,.
Exercise was the most important of these factors.
Only 5% of the men were living a healthy lifestyle (i.e., following at least 4 of these healthy behaviors). Just under half of the 2235 men were non-smokers (46%), and around a third (35%) had an acceptable BMI. Only 15 men ate their “5+” daily (!!), so the requirement was reduced to only three or more portions of fruit and vegetables, enabling 18% to reach it. 39% exercised regularly and 59% reported alcohol intake within the guidelines. Only two men managed five healthy behaviors, and 109 managed four; 19% managed three; 36% two; 31% one; 8% couldn’t manage any.
Elwood, P., Galante, J., Pickering, J., Palmer, S., Bayer, A., Ben-Shlomo, Y., … Gallacher, J. (2013). Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evidence from the Caerphilly Cohort Study. PLoS ONE, 8(12), e81877. doi:10.1371/journal.pone.0081877
A pilot study involving 17 older adults with mild cognitive impairment and 18 controls (aged 60-88; average age 78) has found that a 12-week exercise program significantly improved performance on a semantic memory task, and also significantly improved brain efficiency, for both groups.
The program involved treadmill walking at a moderate intensity. The semantic memory tasks involved correctly recognizing names of celebrities well known to adults born in the 1930s and 40s (difficulty in remembering familiar names is one of the first tasks affected in Alzheimer’s), and recalling words presented in a list. Brain efficiency was demonstrated by a decrease in the activation intensity in the 11 brain regions involved in the memory task. The brain regions with improved efficiency corresponded to those involved in Alzheimer's disease, including the precuneus region, the temporal lobe, and the parahippocampal gyrus.
Participants also improved their cardiovascular fitness, by about 10%.
Smith, J.C. et al. 2013. Semantic Memory Functional MRI and Cognitive Function After Exercise Intervention in Mild Cognitive Impairment. Journal of Alzheimer’s Disease, 37 (1), 197-215.
A study that followed 800 Swedish middle-aged women from 1968 to 2005 has found that high levels of stress in middle age increased Alzheimer’s risk by 21% and risk of any dementia by 15%.
Of the 800 women, 425 died during the course of the study while 153 (19%) developed dementia (of whom 104 developed Alzheimer’s), at an average age of 78. The number of stressors and long-standing distress were independently associated with Alzheimer’s.
The finding doesn’t tell us whether stress is contributing to the development of dementia, or whether it is simply an indicator of another underlying risk factor.
The open access paper is available at https://bmjopen.bmj.com/content/3/9/e003142.abstract.
 Johansson, L., Guo X., Hällström T., Norton M. C., Waern M., Östling S., et al.
(2013). Common psychosocial stressors in middle-aged women related to longstanding distress and increased risk of Alzheimer's disease: a 38-year longitudinal population study.
BMJ Open. 3(9),
A study comparing blood serum levels of the DDT metabolite, DDE, in 86 patients with Alzheimer's disease (average age 74) and 79 controls (average age 70), has found that levels of DDE were 3.8 times higher in 74 of the 86 Alzheimer’s patients (86%). Having the Alzheimer’s gene, APOe4, plus high levels of the pesticide, produced more severe cognitive impairment.
Brain cell studies found that DDE increased production of the amyloid precursor protein (APP).
DDT was banned in the U.S. in 1972, but is still used elsewhere. It also takes a long time to break down in the environment. DDE was found in 75-80% of blood samples collected from the Centers for Disease Control and Prevention for a national health and nutrition survey.
 Richardson, J. R., Roy A., SL S., & et al
(2014). ELevated serum pesticide levels and risk for alzheimer disease.
JAMA Neurology. 71(3), 284 - 290.
A small study involving 52 people aged 32-72 has found that those whose parents both had Alzheimer's disease showed more severe abnormalities in brain volume and metabolism and 5-10% more amyloid plaques in certain brain regions, compared to those with either a father or mother, or neither parent, with the disease. There were 13 in each group.
Consistent with previous research, those whose mother had Alzheimer's disease showed a greater level of the Alzheimer's disease biomarkers than those whose father had the disease.
 Mosconi, L., Murray J., Tsui W. H., Li Y., Spector N., Goldowsky A., et al.
(2014). Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD.
Neurology. 82(9), 752 - 760.
Data from the population-based Finnish Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) study has revealed that healthy dietary choices in midlife may prevent dementia in later years. Out of 2,000 participants, 1,449 took part in the follow-up. The participants were 39 to 64 years old at baseline and 65 to 75 years old at follow-up.
Those who ate the healthiest diet at around age 50 had an almost 90% lower risk of dementia in a 14-year follow-up study than those whose diet was the least healthy.
Healthy foods included vegetables, berries and fruits, fish and unsaturated fats from milk products and spreads; unhealthy foods included sausages, eggs, sweets, sugary drinks, salty fish and saturated fats from milk products and spreads.
Consistent with other research, a high intake of saturated fats was also linked to poorer cognition and an increased risk of mild cognitive impairment 21 years later. A higher saturated fat intake was also associated with an increased risk of dementia among those carrying the “Alzheimer's gene”, ApoE4.
Those consuming 3 to 5 cups of coffee daily had a smaller risk of dementia than those consuming less or more.
Eskelinen, Marjo: The effects of midlife diet on late-life cognition: an epidemiological approach. Publications of the University of Eastern Finland. Dissertations in Health Sciences., no 220. http://epublications.uef.fi/pub/urn_isbn_978-952-61-1394-4/
Eskelinen MH, Ngandu T, Helkala E-L, Tuomilehto J, Nissinen A, Soininen H, Kivipelto M. Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiatry 23(7): 741, 2008.
Laitinen MH, Ngandu T, Rovio S, Helkala E-L, Uusitalo U, Viitanen M, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M. Fat Intake at Midlife and Risk of Dementia and Alzheimer's Disease: A Population-Based Study. Dement Geriatr Cogn Disord 22(1): 99, 2006.
Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M. Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-based CAIDE Study. J Alzheimers Dis 16(1): 85-91, 2009.
Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M. Midlife Healthy Diet Index and Late-Life Dementia and Alzheimer's Disease. Dement Geriatr Cogn Disord Extra 1(1): 103-112, 2011.
A mouse study has found that mice (genetically engineered for Alzheimer’s) who were sleep deprived for eight weeks, not only showed significant cognitive impairment, but also showed a significant increase in the amount of tau protein that became phosphorylated and formed tangles. The other main characteristic of Alzheimer’s, amyloid-beta plaques, was not affected.
The findings are consistent with growing evidence of a link between sleep disturbance and Alzheimer’s, and suggests that chronic sleep disturbance accelerates Alzheimer’s pathology, and should be treated.
The sleep-deprived mice were given 20 hours of light each day, while the control mice were kept on a schedule of 12 hours of light and 12 hours of darkness.
 Di Meco, A., Joshi Y. B., & Praticò D.
(2014). Sleep deprivation impairs memory, tau metabolism, and synaptic integrity of a mouse model of Alzheimer's disease with plaques and tangles.
Neurobiology of Aging. 35(8), 1813 - 1820.
Data from 1.1 million young Swedish men (conscription information taken at age 18) has shown that those with poorer cardiovascular fitness were 2.5 times more likely to develop early-onset dementia later in life and 3.5 times more likely to develop mild cognitive impairment, while those with a lower IQ had a 4 times greater risk of early dementia and a threefold greater risk of MCI. A combination of both poor cardiovascular fitness and low IQ entailed a more than 7 times greater risk of early-onset dementia, and more than 8 times greater risk of MCI.
The increased risk remained even when controlled for other risk factors, such as heredity, medical history, and social-economic circumstances.
The development of early-onset dementia was taken from national disease registries. During the study period, a total of 660 men were diagnosed with early-onset dementia.
A further study of this database, taken from 488,484 men, of whom 487 developed early-onset dementia (at a median age of 54), found nine risk factors for early-onset dementia that together accounted for 68% of the attributable risk. These factors were alcohol intoxication, stroke, use of antipsychotics, depression, father's dementia, drug intoxication other than alcohol, low cognitive function at age 18, low stature at age 18, and high blood pressure at age 18.
 Nyberg, J., Åberg M AI., Schiöler L., Nilsson M., Wallin A., Torén K., et al.
(2014). Cardiovascular and cognitive fitness at age 18 and risk of early-onset dementia.
 P, N., Nordström A., Eriksson M., Wahlund L., & Gustafson Y.
(2013). Risk factors in late adolescence for young-onset dementia in men: A nationwide cohort study.
JAMA Internal Medicine. 173(17), 1612 - 1618.
Data from 1,425 cognitively healthy older adults (70-89) has found that a diagnosis of chronic obstructive pulmonary disease (COPD) was associated with an 83% greater risk of developing non-amnestic mild cognitive impairment. The greatest risk was among patients who had COPD for more than five years.
Over the study period, 230 (16%) developed amnestic MCI, 97 (7%) nonamnestic MCI, 27 (2%) MCI of unknown type, and 16 dementia (1%).
 Singh, B., Mielke M. M., AK P., & et al
(2014). A prospective study of chronic obstructive pulmonary disease and the risk for mild cognitive impairment.
JAMA Neurology. 71(5), 581 - 588.
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