Alzheimer's & other dementias
A long-running study adds to the evidence that high levels of homocysteine increase the risk of developing Alzheimer’s, and higher levels of vitamin B12 help to bring down these levels and reduce risk.
A seven-year study involving 271 Finns aged 65-79 has revealed that increases in the level of homocysteine in the blood were associated with increasing risk of developing Alzheimer’s (each micromolar increase in the concentration of homocysteine increased the risk of Alzheimer's by 16%), while increases in the level of vitamin B12 decreased the risk (each picomolar increase in concentration of B12 reduced risk by 2%). A larger study is needed to confirm this. 17 people (6%) developed Alzheimer’s over the course of the study.
Still, these results are consistent with a number of other studies showing greater risk with higher homocysteine and lower B12. High levels of vitamin B12 are known to lower homocysteine. However, studies directly assessing the effects of B12 supplements have had mixed results. Low levels of B12 are common in the elderly.
 Hooshmand, B., Solomon A., Kåreholt I., Leiviskä J., Rusanen M., Ahtiluoto S., et al.
(2010). Homocysteine and holotranscobalamin and the risk of Alzheimer disease.
Neurology. 75(16), 1408 - 1414.
A very large long-running study has found smoking over two packs per day in middle age more than doubled the chances of developing dementia in later life.
Data from 21,123 people, surveyed between 1978 and 1985 when in their 50s and tracked for dementia from 1994 to 2008, has revealed that those who smoked more than two packs per day in middle age had more than twice the risk of developing dementia, both Alzheimer's and vascular dementia, compared to non-smokers.
A quarter of the participants (25.4%) were diagnosed with dementia during the 23 years follow-up, of whom a little over 20% were diagnosed with Alzheimer's disease and nearly 8% with vascular dementia.
Former smokers, or those who smoked less than half a pack per day, did not appear to be at increased risk. Associations between smoking and dementia did not vary by race or sex.
Smoking is a well-established risk factor for stroke, and is also known to contribute to oxidative stress and inflammation.
 Rusanen, M., Kivipelto M., Quesenberry C. P., Zhou J., & Whitmer R. A.
(2010). Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia.
Arch Intern Med. archinternmed.2010.393 - archinternmed.2010.393.
Another study has come out suggesting that the advantage of mental stimulation is to delay cognitive decline, but at the cost of faster decline later (it’s still a good bargain).
A long-running study involving 1,157 healthy older adults (65+) who were scored on a 5-point scale according to how often they participated in mental activities such as listening to the radio, watching television, reading, playing games and going to a museum, has found that this score is correlated to the rate of cognitive decline in later years.
Some 5 ½ years after this initial evaluation, 395 (34%) were found to have mild cognitive impairment and 148 (13%) to have Alzheimer’s. Participants were then tested at 3-yearly intervals for the next 6 years. The rate of cognitive decline in those without cognitive impairment was reduced by 52% for each point on the cognitive activity scale, but for those with Alzheimer's disease, the average rate of decline per year increased by 42% for each point on the cognitive activity scale. Rate of decline was unrelated to earlier cognitive activity in those with MCI (presumably they were at the balance point).
This is not terribly surprising when you think of it, if you assume that the benefit of mental stimulation is to improve your brain function so that it can better cope with the damage happening to it. But eventually it reaches the point where it can no longer compensate for that damage because it is so overwhelming.
 Wilson, R. S., Barnes L. L., Aggarwal N. T., Boyle P. A., Hebert L. E., Mendes de Leon C. F., et al.
(2010). Cognitive activity and the cognitive morbidity of Alzheimer disease.
Neurology. 75(11), 990 - 996.
Cognitive tests only test you at a particular moment in time; early signs of Alzheimer's are more evident in declines in everyday behavior that are most visible to other people.
Confirming earlier research, a study involving 257 older adults (average age 75) has found that a two-minute questionnaire filled out by a close friend or family member is more accurate that standard cognitive tests in detecting early signs of Alzheimer’s.
The AD8 asks questions about changes in everyday activities:
Problems with two or more of these are grounds for further evaluation. The study found those with AD8 scores of 2 or more were very significantly more likely to have early biomarkers of Alzheimer’s (abnormal Pittsburgh compound B binding and cerebrospinal fluid biomarkers), and was better at detecting early stages of dementia than the MMSE. The AD8 has now been validated in several languages and is used in clinics around the world.
 Galvin, J. E., Fagan A. M., Holtzman D. M., Mintun M. A., & Morris J. C.
(2010). Relationship of dementia screening tests with biomarkers of Alzheimer’s disease.
Brain. 133(11), 3290 - 3300.
A finding that the livers of Alzheimer’s patients have an impaired ability to make the omega-3 fatty acid DHA may suggest a new approach.
Low levels of DHA, an omega-3 fatty acid, have been found in the brains of those with Alzheimer's disease, but the reason has not been known. A new study has found that lower levels of DHA in the liver (where most brain DHA is manufactured) were correlated with greater cognitive problems in the Alzheimer’s patients. Moreover, comparison of postmortem livers from Alzheimer’s patients and controls found reduced expression of a protein that converts a precursor acid into DHA, meaning the liver was less able to make DHA from food.
The findings may explain why clinical trials in which Alzheimer's patients are given omega-3 fatty acids have had mixed results. They also suggest that it might be possible to identify at-risk persons using specific blood tests, and perhaps delay the development of Alzheimer’s with a chemically enhanced form of DHA.
 Astarita, G., Jung K-M., Berchtold N. C., Nguyen V. Q., Gillen D. L., Head E., et al.
(2010). Deficient Liver Biosynthesis of Docosahexaenoic Acid Correlates with Cognitive Impairment in Alzheimer's Disease.
PLoS ONE. 5(9), e12538 - e12538.
A review of brain imaging and occupation data from 588 patients diagnosed with frontotemporal dementia has found that among the dementias affecting those 65 years and younger, FTD is as common as Alzheimer's disease. The study also found that the side of the brain first attacked (unlike Alzheimer’s, FTD typically begins with tissue loss in one hemisphere) is influenced by the person’s occupation.
Using occupation scores that reflect the type of skills emphasized, they found that patients with professions rated highly for verbal skills, such as school principals, had greater tissue loss on the right side of the brain, whereas those rated low for verbal skills, such as flight engineers, had greater tissue loss on the left side of the brain. This effect was expressed most clearly in the temporal lobes of the brain. In other words, the side of the brain least used in the patient's professional life was apparently the first attacked.
These findings are in keeping with the theory of cognitive reserve, but may be due to some asymmetry in the brain that both inclines them to a particular occupational path and renders the relatively deficient hemisphere more vulnerable in later life.
 Spreng, R. Nathan, Rosen H. J., Strother S., Chow T. W., Diehl-Schmid J., Freedman M., et al.
(2010). Occupation attributes relate to location of atrophy in frontotemporal lobar degeneration.
Neuropsychologia. 48(12), 3634 - 3641.
A safety trial has shown that Deep Brain Stimulation is safe for those with mild Alzheimer’s, and may slow cognitive decline.
A pilot study involving six patients with mild Alzheimer’s has shown using Deep Brain Stimulation (DBS) is safe and may help improve memory, or at least slow decline. Patients received continuous stimulation for 12 months, between 2005 and 2008. Impaired glucose utilization in the temporal and parietal lobes was dramatically reversed early in the treatment, and maintained after the year of continuous stimulation. Performance on cognitive tests showed possible improvement and/or slowing in the rate of cognitive decline at 6 and 12 months in three of the six patients.
The principal aim of this pilot study was to assess the safety of the procedure, and it is now hoped to move on to a larger study to assess its effectiveness. Anyone interested in more information about participating in the next phase should visit: http://www.uhn.on.ca/Focus_of_Care/KNC/Functional_Neurosurgery/research.asp.
 Laxton, A. W., Tang-Wai D. F., McAndrews M P., Zumsteg D., Wennberg R., Keren R., et al.
(2010). A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease.
Annals of Neurology. n/a-n/a - n/a-n/a.
A two-year study involving 271 older adults (70+) with mild cognitive impairment has found that the rate of brain atrophy in those taking folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), was significantly slower than in those taking a placebo, with those taking the supplements experiencing on average 30% less brain atrophy. Higher rates of atrophy were associated with lower cognitive performance. Moreover those who with the highest levels of homocysteine at the beginning of the trial benefited the most, with 50% less brain shrinkage. High levels of homocysteine are a risk factor for Alzheimer’s, and folate, B12 and B6 help regulate it.
The finding that atrophy can be slowed in those with MCI offers hope that the treatment could delay the development of Alzheimer’s, since MCI is a major risk factor for Alzheimer’s, and faster brain atrophy is typical of those who go on to develop Alzheimer’s.
 Smith, D. A., Smith S. M., de Jager C. A., Whitbread P., Johnston C., Agacinski G., et al.
(2010). Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial.
PLoS ONE. 5(9), e12244 - e12244.
A long-running study of Swedish women has revealed that dementia risk is greater in those who experienced periods of stress in middle age.
Data from a 35-year study of women from Gothenburg in Sweden has revealed that the risk of dementia was about 65% higher in women who reported repeated periods of stress in middle age than in those who did not. The risk increased with number of periods of stress, with women who reported stress on all three occasions they were asked (1968, 1974 and 1980) having more than double the risk of dementia. Stress was defined as a sense of irritation, tension, nervousness, anxiety, fear or sleeping problems lasting a month or more due to work, health, family or other problems. Of the 1462 women in the sample used, 11% developed dementia, 65% of which was Alzheimer’s and 25% vascular dementia.
 Johansson, L., Guo X., Waern M., Ostling S., Gustafson D., Bengtsson C., et al.
(2010). Midlife psychological stress and risk of dementia: a 35-year longitudinal population study.
Brain. 133(8), 2217 - 2224.
A very large study has found that military veterans with PTSD were twice as likely to develop dementia in old age, compared to vets without PTSD.
A study involving over 180,000 older veterans (average age 68.8 at study start), of whom 29% had PTSD, has revealed that those with PTSD had a significantly greater risk of developing dementia. Over the seven years of the study, 10.6% of the veterans with PTSD developed dementia compared to 6.6% of those without PTSD. When age was used as the time scale, the risk for those with PTSD was more than double. Results were similar when those with a history of head injury, substance abuse, or clinical depression, were excluded.
One possibility for the link is that the stress induced by PTSD contributes to the development of dementia.
 Yaffe, K., Vittinghoff E., Lindquist K., Barnes D., Covinsky K. E., Neylan T., et al.
(2010). Posttraumatic Stress Disorder and Risk of Dementia Among US Veterans.
Arch Gen Psychiatry. 67(6), 608 - 613.
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