Alzheimer's & other dementias
Alzheimer's disease currently affects one in 10 people over age 65 and nearly half of those over age 85.
More than 19 million Americans say they have a family member with the disease, and 37 million say they know somebody affected with Alzheimer's.
In the United States, the average lifetime cost per Alzheimer patient is US$174,000. (These figures are from the U.S. Alzheimer's Association).
For information about Alzheimer's, see the Alzheimer's Disease Education and Referral (ADEAR) Center's website (www.alzheimers.org). ADEAR is run by the National Institute on Aging (one of the US Government's National Institutes of Health).
Other useful resources include:
The Alzheimer Research Forum: "A scientific knowledge base on Alzheimer disease, with research news, expert commentaries, and databases for peer-reviewed articles, drugs, research reagents, grants, jobs, conferences, and more."www.alzforum.org
Cognitive Neurology and Alzheimer's Disease Center at Northwestern Universityhttp://www.brain.northwestern.edu/mdad/index.html
http://www.alz.org/ Site of the U.S. Alzheimer’s Association.
http://www.alzheimers.org.uk/ Site of the U.K. Alzheimer's Society
http://www.alzheimer.ca/ Site of the Canadian Alzheimer's Association
http://www.alzheimers.org.au/ Site of the Australian Alzheimer's Association
www.alzheimers.org.nz Site of Alzheimer's New Zealand
a good introduction from the Harvard Mahoney Neuroscience Newsletter:
Montessori for Alzheimer's patients
Movement with Meaning
After Alzheimer's disease, the second most common neurodegenerative disorder is Parkinson’s disease. In the U.S., at least 500,000 are believed to have Parkinson’s, and about 50,000 new cases are diagnosed every year1 (I have seen other estimates of 1 million and 1.5 million — and researchers saying the numbers are consistently over-estimated while others that they are consistently under-estimated!). In the U.K., the numbers are 120,000 and 10,0002.
Part of the problem in estimating national and global prevalence is that Parkinson's is very much affected by environmental factors. The Amish, Nebraska, the area around the ferromanganese plants in Breccia (Italy), and the Parsi of Mumbai (India), have the highest rates of Parkinson's in the world. Pesticide use, and some occupations and foods, are all thought to increase the risk of Parkinson's. So is head trauma.
There may also be ethnic differences. A recent analysis of Medicare data3 from more than 450,000 patients with PD in the United States has found substantial variation between whites, African Americans, and Asians, with whites showing dramatically greater rates (158.21 per 100,000 in white men compared to 75.57 and 84.95 for African Americans and Asians, respectively). These differences, however, may well reflect factors other than ethnicity, given the significant role that environmental factors play in Parkinson's. Most patients were found to live in the Midwest and Mid-Atlantic regions (areas with very high proportions of whites).
Of course Parkinson’s, like Alzheimer’s, is a disorder of age (although in both cases, a minority suffer early onset). Figures from a 1997 European study4 that estimated the overall, age-adjusted prevalence in Europe at 1.6% gave this age breakdown:65-69: 0.6%70-74: 1.0%75-79: 2.7%80-84: 3.6%85-89: 3.5%As you can see, there is a sharp rise in the later half of the 70s, rising to a peak in the 80s (studies suggest it declines in the 90s).
Parkinson’s is of course primarily a movement disorder, not a cognitive one. However, it can lead to dementia. As with the numbers of Parkinson's sufferers, the risk of that is so variously estimated that estimates range from 20-80%!
Part of the problem is disentangling mortality — as with Alzheimer’s, many die before the symptoms of dementia have had time to develop. It is helpful to deconstruct that top statistic.
The 2003 Norwegian study5 that appears to be the source of this 80% calculated an 8-year prevalence estimate of 78.2% from an 8 year study involving 224 Parkinson’s patients. At the beginning of the study, 51 of these 224 had dementia. After 4 years, 36 of the non-demented had died, and 7 refused to continue their participation; of the 51 demented, 42 had died (according to my calculations – this figure, and several others, were not given). Of the 139 patients remaining in the study at year 4, 43 of the previously non-demented had developed dementia, meaning (according to my calculations) that 52 in total now had dementia, and 87 had not. After another 4 years, there were only 87 patients remaining in the study, 19 of those 87 non-demented having died, a further 3 refusing to continue, and (my calculation) 30 of the 52 demented having died. At this time, year 8, 28 of the previously non-demented had now developed dementia, leaving (my calculation) 37 non-demented survivors.
In other words, over a period of 8 years, after having had Parkinson’s for over 9 years, on average, when the study began, just over half (54.5%; 122/224) developed dementia. About the same number (56.7%; 127) had died. At that point, after having had Parkinson’s for an average of 17 years (they were now on average 73 years old), 50 (22%) were still alive but with dementia, and 37 (16.5%) were still alive and non-demented (the percentage is only slightly increased by subtracting those who refused to continue participating).
Importantly, those 37 had no more cognitive decline than was evident in age-matched controls.
Note also that the average life expectancy after being diagnosed with Parkinson's is about 9 years -- hence, those who participated were already at this point at the beginning of the study. We don't know how many people developed dementia and died between diagnosis and the study beginning, but we do know that 23% (51/224) had dementia at the beginning of the study, after having had Parkinson's for an average of 11 years (their average was higher than the group average) -- which is already longer than the average survival rate.
In other words, we need a study that follows PD sufferers from diagnosis until death to truly give an accurate estimate of the likelihood of developing dementia before death. We can however give an estimate of how many people survive PD for 17 years (nearly twice the average survival time) without developing dementia: 16.5% -- which is approaching half (42.5%) the number of people who survive that long.
We can also estimate how many PD sufferers who have had PD for an average of 9 years will not have dementia: 77% (173/224 — the number of non-demented at the beginning of the study). And how many will not have dementia after 13 years: 63% (87/139 — the number of non-demented at year 4 of the study).
The big question is of course, are there any signs that indicate which individuals will develop dementia. The researchers found6 that age, hallucinations, and more severe motor problems were all risk factors for developing dementia.
Check out this youtube video: http://www.youtube.com/watch?v=ZPnpmVWU0Hk
See these websites:
Check out these books:http://www.amazon.com/Dementia-Lewy-Bodies-Parkinsons-Disease/dp/1841843954
Vascular dementia, as its name suggests, is caused by poor blood flow, produced by a single, localized stroke, or series of strokes.
It is the second most common dementia, accounting for perhaps 17% of dementias. It also co-occurs with Alzheimer's in 25-45% of cases. Although there are other types of dementia that also co-occur with Alzheimer's, mixed dementia generally refers to the co-occurrence of Alzheimer's and vascular dementia.
In general, unsurprisingly, vascular dementia has the same risk factors as cerebrovascular disease.
A study1 of 173 people from the Scottish Mental Survey of 1932 who have developed dementia has found that, compared to matched controls, those with vascular dementia were 40% more likely to have low IQ scores when they were children than the people who did not develop dementia. Because this was not true for those with Alzheimer's disease, it suggests that low childhood IQ may act as a risk factor for vascular dementia through vascular risks rather than the "cognitive reserve" theory.
The exciting thing about vascular dementia is that it is far more preventable than other forms of dementia. As with risk, as a general rule, the same things that help you protect you from heart attacks and stroke will help protect you from vascular dementia. This means diet, and it means exercise.
A four-year study2 involving 749 older adults has found that the top one-third of participants who exerted the most energy in moderate activities such as walking were significantly less likely to develop vascular dementia than those people in the bottom one-third of the group.
Apart from normal medical treatment for cerebrovascular problems, there are a couple of interesting Chinese studies that have looked specifically at vascular dementia.
The herb gastrodine has been used in China for centuries to treat disorders such as dizziness, headache and even ischemic stroke. A 12-week, randomized, double-blind trial3 involving 120 stroke patients who were diagnosed with mild to moderate vascular dementia has found that gastrodine and Duxil® (a drug used to treat stroke patients in China) produced similar overall levels of cognitive improvement -- although more patients showed 'much improvement' with gastrodine (23% vs 14%).
A Chinese pilot study4 involving 25 patients with mild to moderate vascular dementia found that ginseng compound significantly improved their average memory function after 12 weeks, but more research (larger samples, placebo-controls) is needed before this finding can be confirmed. Five years on I have still not seen such a study.
Lewy Body Dementia is so called because the brains of affected people develop abnormal spherical masses of protein, called Lewy bodies, inside nerve cells. Lewy bodies are associated with Parkinson’s disease as well as dementia. Thus Lewy body dementia can refer to both Parkinson’s disease dementia and “dementia with Lewy bodies”. Lewy bodies are also often found in the brains of those with Alzheimer’s disease.
Unlike Alzheimer’s, however, dementia with Lewy bodies characteristically (but not invariably) begins with visual hallucinations.
Estimates of its prevalence are complicated by the lack of clearly defined clinical criteria, and vary widely. A 2005 review1 concluded that the range probably falls between 0 to 5% in the general population, and from 0 to 30.5% of all dementia cases (the very broad range reflects the confusion between Parkinson’s disease dementia (PDD), dementia with Lewy bodies, and Alzheimer’s where Lewy bodies are present).
A comparison of these three disorders found that cognitive impairment in those with Alzheimer's disease and those with Lewy body dementia was similar, and more severe than in those with Parkinson's disease dementia.
The 1997 study2 also found that a simple test, in which patients are asked to draw and copy a clock face, distinguished those with Alzheimer’s and those with Lewy body dementia — of all the groups, only those with Lewy body dementia had equally poor scores in the “copy” part of the test compared to the “draw” part.
Mayo Clinic: http://www.mayoclinic.com/health/lewy-body-dementia/DS00795
Lewy Body Dementia Association: http://www.lewybodydementia.org/
Frontotemporal dementia is a disorder of the frontal lobes and includes what was known as primary progressive aphasia. Although it occurs far less often than Alzheimer's disease, among dementia sufferers younger than 65 it is estimated to occur at about the same rate. In other words, frontotemporal dementia is, unlike the most common dementias, not a disorder of age. Most sufferers become symptomatic in their 50s and 60s.
Frontotemporal dementia generally begins with a focal symptom, such as aphasia, before (usually a number of years later) progressing to more generalized dementia.
There are several types of frontotemporal dementia. The most common (around 60% of FTD cases) is known as the behavioral variant (also, Pick's disease). This is characterized by impairment in social and emotional skills. The other 40% of FTD cases have language impairments -- about half of these suffer from semantic FTD, characterized by difficulties in remembering the meanings of words; the other half suffer from progressive nonfluent aphasia, characterized by difficulties in producing language (although they understand what they're trying to say).
In around 15% of FTD cases (most usually the behavioral variant), motor neurone disease also develops.
A large-scale epidemiological study1 in the Netherlands indicated frontotemporal dementia occurs at a rate of 1.1 per 100,000, with the prevalence highest among those ages 60 to 69, at 9.4 per 100,000. The prevalence among people ages 45 to 64 was estimated to be 6.7 per 100,000 (this was after autopsies caused the number of diagnosed cases to go up, with 17 of 50 patients undiagnosed in life). Unlike other forms of dementia, where most occurrences begin in older adults, symptoms began after age 65 in only 22% of patients. The median age of onset was 58, with a range from 33 to 80.
A family history of dementia was present in 43% of patients. Interestingly, whites accounted for 99% of all cases despite an ample nonwhite population.
A large U.K. study2 found prevalences of early-onset FTD and Alzheimer's were the same in the 45-64 population: 15 per 100,000. The mean age at onset of FTD was 52.8 years and there was a striking male preponderance (14:3).
This rate is notably higher than that found in the Dutch study, and it has been suggested that the reason is ethnicity -- the Dutch study, as mentioned, had a significant proportion of non-Caucasians, while the British (Cambridge) study explicitly mentioned that minorities were under-represented.
It has been estimated that frontotemporal dementia accounts for approximately 8% of patients with dementia, but this is now thought to be an underestimation.
There is a high level of genetic involvement in this type of dementia.
As mentioned, the Dutch study found a family history of dementia in 43% of FTD patients. Another large Dutch study3 found 38% of FTD patients had one or more first-degree relatives with dementia before age 80 compared to 15% of age-matched controls; 10% had two or more first-degree relatives with dementia compared with 0.9% of the controls. FTD patients were also three times more likely to have 2 "Alzheimer's genes" (2 e4 alleles of the ApoE gene) than the controls: 7% vs 2.3%.
This study also supports findings with other dementias that earlier-onset is more likely to have genetic causes. First-degree relatives of FTD patients (who had twice the risk of dementia before age 80 compared with relatives of controls) were much more likely to develop dementia early: age of onset of dementia in affected first-degree relatives of FTD patients averaged was just under 61, compared to 72.3 for affected first-degree relatives of controls.
The genes implicated in familial cases of FTD are on chromosome 17, in the gene for the tau protein, and in the gene for the progranulin protein. Research4 has now confirmed that people with these hereditable defects produce only half of the normal amount of progranulin, and recently a simple test for measuring the quantity of progranulin in the blood was developed. The test reveals whether someone has the mutations that carry an increased risk of FTD.
A recent study5 involving 225 FTD patients found 41.8% of patients had some family history, although only 10.2% had a clear autosomal dominant history (at least 3 cases within the last 2 generations). However, the importance of genes varied across the different clinical subtypes of the disease, with the behavioral variant being the most heritable and FTD–motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable.
Dementia is estimated1 to afflict over 35.5 million people worldwide -- this includes nearly 10 million people in Europe, nearly 4.4 million in North America, nearly 7 million in South and Southeast Asia, about 5.5 million in China and East Asia and about 3 million in Latin America.
The estimated prevalence for over 60s is 4.7% worldwide. Because this is a disorder of age, prevalence is of course greatly affected by the proportion of people reaching their senior years. Hence the prevalence is higher in the more developed countries: the estimated prevalence in Western Europe and North America is 7.2% and 6.9% respectively, compared to 2.6% in Africa.
The prevalence of the various dementia types is a complicated story. Certainly Alzheimer's disease is by far the most common type of dementia, accounting for perhaps 70% of all dementias (although a 2006 study13 suggested that non-Alzheimer dementias were as common as Alzheimer's — however this was based on dementia among military veterans). The second most common dementia is almost certainly vascular dementia, which may account for some 17% of dementias. However, the actual numbers are made uncertain by the fact that these two dementias often occur together.
At minimum, around a quarter of Alzheimer's cases have been found, on autopsy, to also have vascular pathology; this proportion reaches higher levels when the samples are not restricted to dementia clinics. One such community-based study2, for example, found 45% of the Alzheimer's cases also showed significant vascular pathology. Another, U.K., study3 found a similar proportion (46%).
Another, large long-running, study14 has found that only 30% of people with signs of dementia had Alzheimer’s disease alone. 42% had Alzheimer’s disease with cerebral infarcts (strokes) and 16% had Alzheimer’s disease with Parkinson’s disease (including two people with all three conditions). Infarcts alone caused another 12% of the cases. Vascular dementia caused another 12%.
Although there are other types of dementia that also co-occur with Alzheimer's, mixed dementia generally refers to the co-occurrence of Alzheimer's and vascular dementia.
The other important dementia type that co-occurs with Alzheimer's at a high rate is dementia with Lewy bodies, also considered to be one of the most common dementias (although, due to inconsistent criteria, estimates of its actual prevalence vary wildly). It is estimated to co-occur with Alzheimer's pathology around half the time. At a lesser frequency, but still high, is Parkinson's disease dementia — about 20% of Alzheimer's patients also have Parkinson's disease.
But it is probably fair to say that the distinction between these dementia types is not clear-cut. Lewy bodies are found in a high proportion of both Alzheimer's and Parkinson's patients — the number of cases of 'pure' Lewy body dementia is much smaller. It's been said, in fact, that the main difference between Lewy body dementia and Parkinson's disease dementia lies in the timing — Parkinson's disease dementia will be preceded by at least a year and more likely a number of years, by full-blown Parkinson's disease.
Regardless of the difficulties in establishing clear clinical criteria, however, there is no doubt that Alzheimer's co-occurs with vascular pathology or Lewy body pathology at a startlingly high rate.
One of the problems with clearly distinguishing between these types of dementia is a happy one: vascular and Alzheimer's pathology can be found, at autopsy, in many elderly brains that have not shown symptoms of dementia.
For example, in one community-based study4, in which the median age at death was around 85 for the 209 individuals, 48% had had dementia, of whom 64% showed Alzheimer's pathology. However, 33% of those who had not had dementia showed similar levels of Alzheimer's plaques. Similarly, some amount of tau tangles (another aspect of Alzheimer's pathology) was found in 61% of the demented and 34% of the non-demented individuals. Finally, multiple vascular pathology was found in 46% of the demented group and 33% of the non-demented, and vascular lesions were equally common in both.
And in the large long-running study mentioned earlier14, in those without dementia, brain autopsy revealed the presence of Alzheimer’s in 24% of cases, and infarctions in 18%.
The question of how likely any person is to develop dementia must begin with estimates of prevalence, but this of course is only the very beginning of the story.
Estimating prevalence is complicated by the fact that dementia is greatly affected by lifestyle, environmental, and genetic factors, and consequently prevalence varies a lot depending on geographic region.
Different dementia sub-types have different causes, and some give a much greater weight to genetic or environmental factors than others. However, the finding that dementia risk is much greater in those with more than one pathology, and that Alzheimer’s pathology with cerebral infarcts is a very common combination, adds to growing evidence that dementia risk might be reduced with the same tools we use for cardiovascular disease such as control of blood cholesterol levels and hypertension.
The first American study to use nationally representative data5 (rather than extrapolating from regional data) came up with a figure of 13.9% of those aged 71 and older (one in seven). But age of course makes all the difference in the world. The study found 5% of those aged 71 to 79, rising to 37.4% of those age 90 and older.
Although all the dementia types show an increase with age, Alzheimer's is particularly a disorder of age: although the study found only 46.7% of those with dementia in their 70s had Alzheimer's, for those in their 90s, Alzheimer's was the dementia type for 79.5% of them.
An Italian study of over 2000 seniors over 80 years old6 confirms that dementia does indeed keep increasing with age (it had been thought that risk leveled off for those who reached their 90s). The study found that 13.5% of those aged 80 to 84 had dementia, rising sharply to 30.8% of those 85 to 89, 39.5% of those 90 to 94, and 52.8% among those older than 94.
A number of studies have found differences between men and women, or between difference ethnicities, but this large, nationally representative study found that, although on the face of it there were race and gender differences, these differences disappeared once age, years of education, and presence of at least one "Alzheimer's gene" was taken into account.
However, an American study of over 900 seniors over 90 years old7 found that women of this age were much more likely to have dementia than men (some 45% of them, compared to 28% of the men), and that the likelihood of having dementia kept increasing with age for the women, but not for the men. Of course, more women than men survive to this age (some two-thirds of the participants were women).
Interestingly, education was protective for the women (the risk of dementia decreasing the more years of education the individual had had) but not for the men. The study participants were not, however, a random sampling -- they all came from the same retirement community, and most were white and of high socioeconomic status. Given that, and considering the times in which they were born, it seems likely that there would be far more variability in educational level among the women than the men. The men, while less likely to develop dementia, did tend to decline faster if they did develop it.
The Italian oldest-old study, too, found more women than men had dementia: across all ages, 25.8% of the women and 17.1% of the men.
These figures don't of course tell us how many develop dementia at those ages. Obviously, survival rates are a factor, and as we saw in the other study, male and female survival rates do vary. The figures for new cases of dementia developing in these age bands were:
These figures make even more clear what was apparent in the earlier figures: dementia jumps suddenly in the later half of the 80s, and again in the later half of the 90s.
Importantly, however, the incidence of new cases shows us how important the gender difference in survival rates is: the difference in prevalence is much smaller in these terms --9.2% among women and 7.2% among men.
The study, which canvassed everyone in the age group within a specific geographical area and had an 88% response rate, had a ratio of 74 women to 26 men. Because the number of men at the very highest ages was so small, we can't draw any firm conclusions about gender differences at those ages.
The Italian study involves a very different population from that of the American study: Varese is in a heavily industrialised part of northern Italy, with a high immigrant population, and the average amount of education was only 5.1 years.
A review of 26 studies looking at dementia prevalence in Europe8 confirmed rates for men rising from 1.8% in the 65-69 years age range up to 30% in the over 90 years age group, and for women rising from 1.5% to 30% in the 80-85 years age band. However (and confirming the American study), rates in the oldest old for women rose to over 50% in those over 95 years.
The average age at the onset of dementia is around 80 years. Early-onset dementia is defined arbitrarily (and variably) as occurring before 60-65. Early-onset cases have been estimated to make up about 6-7% of all cases of Alzheimer's disease, and though a lot of attention has been given to them, only about 7% of early-onset cases are in fact familial9.
Familial cases involve mutations in specific genes (the APP or presenilin genes); they do not include what is popularly referred to as the "Alzheimer's gene" — variants of APOE. A 1995 study10 calculated that a person with no family history of Alzheimer's disease who has an e4 allele has a lifetime risk of 29%, compared to a risk of 9% if they don't have an e4 allele. In other words, if you don't have any of the Alzheimer's risk genes, or any family history, you only have a 9% risk of developing Alzheimer's, and even if you do have the "Alzheimer's gene", your chance of not getting Alzheimer's is still over 70%. Your risk does, however, go up dramatically if both your APOE alleles are e4.
A large study11 found, however, that there were both ethnic and gender differences for the risk of this genetic factor. The effect of having an e4 allele was much greater among Japanese compared to Caucasian, and greater for Caucasian compared to African American and Hispanic. Additionally, the effect of having an e4 allele becomes less significant after 70.
There is evidence12 that the age of onset for both Alzheimer's and Parkinson's diseases, for those genetically disposed, is controlled by genes on chromosome 10.
A study involving 95 healthy older adults found that adults reporting a decline in sleep quality in their 40s and 50s had more amyloid-beta in their brains later in life, while those reporting poorer sleep in their 50s and 60s had more tau tangles. Those with high levels of tau protein were more likely to lack the synchronized brain waves during deep NREM sleep that are associated with a good night's sleep, and the more tau protein, the less synchronized these brain waves were.
Previous research has found that a dip in the amplitude of slow wave activity during deep NREM sleep was associated with higher amounts of beta-amyloid in the brain and memory impairment.
Studies of healthy animals and humans have reported higher levels of amyloid beta after a single night of sleep deprivation, and that disruption of slow-wave sleep causes amyloid beta levels to rise as much as 30%. Moreover, a single night’s sleep deprivation has been found to increase tau levels by as much as 50% in cerebrospinal fluid.
These findings suggest that quality sleep helps the body clear excess amyloid and tau proteins.
A preliminary study involving 20 healthy subjects aged 22 to 72 found beta-amyloid increases of about 5% after losing a night of sleep.
Many researchers believe the link between sleep disorders and Alzheimer's risk is "bidirectional," since elevated beta-amyloid may also lead to sleep disturbances.
A very small study involving eight people aged 30-60, who experienced (over time) two or three different sleep situations, found that amyloid beta levels were 25-30% higher when individuals had a a sleepless night — putting those amyloid beta levels on par with the levels seen in people genetically predisposed to develop Alzheimer’s at a young age.
A sleep study involving 17 healthy adults aged 35 to 65, found that those whose slow-wave sleep was disrupted (by a beeping sound that moved them into a shallower sleep) found a 10% increase in amyloid beta levels after a single night of interrupted sleep, but no corresponding increase in tau levels. However, participants whose activity monitors showed they had slept poorly at home for the week before showed a spike in levels of tau.
Data from 2,457 older adults (65+) in the Framingham study found that those who consistently slept more than nine hours every night had twice the risk of developing dementia and Alzheimer’s disease within the next 10 years, compared to those who slept less than nine hours a night.
Over the 10-year study period, 234 were diagnosed with dementia.
It’s suggested that one reason might be that those with depression tend to sleep longer. In any case, it’s thought that the longer sleep sessions reflect something else going on, rather than being a cause.
Education level also affected the degree of risk. Those without a high school degree who slept more than nine hours nightly had a 600% greater risk of later receiving a dementia diagnosis than people with a high school degree.
A ten-year Japanese study involving 1,517 older adults (60+) found that dementia rates were higher in those with daily sleep duration of less than 5 hours or more than 10 hours, compared with those with daily sleep duration of 5-6.9 hours. However, those with short sleep duration who had high physical activity did not have a greater risk of dementia.
294 participants (19%) developed dementia in the 10 year period.
A study involving 321 older adults (60+; average age 67), who participated in a sleep study between 1995 and 1998, found poorer REM sleep was associated with an increased risk of developing dementia over 12 years.
During that period, 32 people were diagnosed with some form of dementia (24 with Alzheimer’s)
Those who developed dementia spent an average of 17% of their sleep time in REM sleep, compared with 20% for those who didn’t develop dementia. For every percent that REM sleep was reduced, there was a 9% increase in dementia risk, and an 8% increase in Alzheimer’s risk specifically.
No such associations were found for other stages of sleep, although that shouldn’t be taken to mean that other sleep stages don’t affect key features of Alzheimer’s.
A study involving 288 cognitively healthy older adults (65+) found that those who had sleep apneas had on average 4.5% higher levels of tau in the entorhinal cortex than those who did not have apneas, after controlling for several other factors that could affect levels of tau in the brain, such as age, sex, education, cardiovascular risk factors and other sleep complaints.
15% (43 participants) were reported by their bed partners as having sleep apneas.
This preliminary study was presented at the American Academy of Neurology's 71st Annual Meeting in Philadelphia, May 4-10, 2019.
Data from 1,752 older adults found that sleep-disordered breathing was associated with poorer attention and processing speed. In particular, increased overnight hypoxemia (oxygen saturation below 90%) was linked with poorer attention and memory, and more daytime sleepiness associated with poorer attention and memory and slower cognitive processing speed.
These associations were strongest in APOE-ε4 carriers.
 Winer, J. R., Mander B. A., Helfrich R. F., Maass A., Harrison T. M., Baker S. L., et al.
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A 10-year South Korean study using data from 262,349 older adults (50+) has found that those with chronic periodontitis had a 6% higher risk for dementia than did people without periodontitis. This connection was true despite behaviors such as smoking, consuming alcohol, and remaining physically active.
Gum disease has been linked to Alzheimer's as a risk factor, and now an animal study provides evidence that Porphyromonas gingivalis (Pg), the bacterium associated with chronic gum disease, colonizes the brain and increases production of amyloid beta.
Moreover, the bacterium's toxic enzymes (gingipains) have been found in the neurons of patients with Alzheimer’s. Gingipain levels were associated with two markers: tau, and ubiquitin (a protein tag that marks damaged proteins).
When molecule therapies targeting Pg gingipains were applied, there was reduced bacterial load of an established Pg brain infection, blocked amyloid-beta production, reduced neuroinflammation and protected neurons in the hippocampus.
Around half the population are said to have this bacteria in some form, and around 10% of those with the bacteria will develop serious gum disease, loose teeth, and have an increased risk of developing Alzheimer´s disease.
A mouse study found that long-term exposure to periodontal disease bacteria resulted in significantly higher amounts of amyloid beta plaque, more brain inflammation and fewer intact neurons. It’s important to note that the mice used in the study were not genetically engineered to develop Alzheimer's.
 Choi, S., Kim K., Chang J., Kim S. Min, Kim S. Jip, Cho H-J., et al.
(2019). Association of Chronic Periodontitis on Alzheimer's Disease or Vascular Dementia.
Journal of the American Geriatrics Society. 67(6), 1234 - 1239.
 Dominy, S. S., Lynch C., Ermini F., Benedyk M., Marczyk A., Konradi A., et al.
(2019). Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors.
Science Advances. 5(1), eaau3333.
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(2018). Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice.
PLOS ONE. 13(10), e0204941.
Brain scans from over 4,000 people, across the age range (9 months to 94 years) and including 1,385 Alzheimer's patients, has revealed an early divergence between those who go on to develop Alzheimer’s and those who age normally. This divergence is seen in early atrophy of the hippocampus before age 40, and in the amygdala around age 40.
 Coupé, P., Manjón J. Vicente, Lanuza E., & Catheline G.
(2019). Lifespan Changes of the Human Brain In Alzheimer’s Disease.
Scientific Reports. 9(1), 1 - 12.
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