Dietary changes affect levels of biomarkers associated with Alzheimer's

In a study involving 20 healthy older adults (mean age 69.3) and 29 older adults who had amnestic mild cognitive impairment (mean age 67.6), half the participants were randomly assigned to a high–saturated fat/high–simple carbohydrate diet (HIGH) and half to a low–saturated fat/low–simple carbohydrate diet (LOW) for four weeks, in order to investigate the effects on biomarkers associated with Alzheimer’s.

For the healthy participants, the LOW diet decreased the level of amyloid-beta 42 in the cerebrospinal fluid, while the HIGH diet increased its level. The HIGH diet also lowered the CSF insulin concentration. For those with aMCI, the LOW diet increased the levels of amyloid-beta 42 and increased the CSF insulin concentration. For both groups, the level of apolipoprotein E in the CSF increased in the LOW diet and decreased in the HIGH diet.

For both groups, the LOW diet improved performance on delayed visual recall tests, but didn’t affect scores on other cognitive measures (bear in mind that the diet was only followed for a month).

The researchers suggest that the different results of the unhealthy diet in participants with aMCI may be due to the diet’s short duration. The fact that diet was bringing about measurable changes in CSF biomarkers so quickly, and that the HIGH diet moved healthy brains in the direction of Alzheimer’s, speaks to the potential of dietary intervention.

Why coffee helps protect against Alzheimer's disease

Support for the value of coffee in decreasing the risk of Alzheimer’s comes from a mouse study, which found that an as yet unidentified ingredient in coffee interacts with caffeine in such a way that blood levels of a growth factor called GCSF (granulocyte colony stimulating factor) increases. GCSF is a substance greatly decreased in patients with Alzheimer's disease and demonstrated to improve memory in Alzheimer's mice.

The finding points to the value of caffeinated coffee, as opposed to decaffeinated coffee or to other sources of caffeine. Moreover, only "drip" coffee was used; the researchers caution that they don’t know whether instant caffeinated coffee would provide the same GCSF response.

There are three ways that GCSF seems to improve memory performance in the Alzheimer's mice: by recruiting stem cells from bone marrow to enter the brain and remove beta-amyloid protein; by increasing the growth of new synapses; by increasing neurogenesis.

The amount of coffee needed to provide this protection, however, is estimated to be about 4 to 5 cups a day. The researchers also believe that this daily coffee intake is best begun at least by middle age (30s – 50s), although starting even in older age does seem to have some protective effect.

Weirdly (I thought), the researchers remarked that "The average American gets most of their daily antioxidants intake through coffee". Perhaps this points more to the defects in their diet than to the wonders of coffee! But the finding is consistent with other research showing an association between moderate consumption of coffee and decreased risk of Parkinson's disease, Type II diabetes and stroke.

A just-completed clinical trial has investigated GCSF treatment to prevent Alzheimer's in patients with mild cognitive impairment, and the results should be known soon.

Functional impairment good indicator of mild cognitive impairment

Evaluation of 816 older adults, of whom 229 had no cognitive problems, 394 had a diagnosis of amnestic mild cognitive impairment, and 193 had a diagnosis of mild Alzheimer’s, has revealed that most of those with aMCI (72%) or AD (97%) had trouble with at least one type of function on the Pfeffer Functional Activities Questionnaire. Only 8% of controls had any difficulty. In both impaired groups, those who had the most difficulty functioning also tended to score worse on cognition tests, have smaller hippocampal volumes, and carry the APOe4 gene.

Two of the ten items in the questionnaire were specific in differentiating the control group from the impaired groups. Those items concerned "remembering appointments, family occasions, holidays, and medications” and "assembling tax records, business affairs, or other papers." Only 34% of those with aMCI and 3.6% of those with AD had no difficulty with these items.

The findings suggest that even mild disruptions in daily functioning may be an important clinical indicator of disease.

Early-onset Alzheimer’s poorly diagnosed when initial symptoms aren’t memory related

Post-mortem analysis of 40 people diagnosed  with early-onset Alzheimer’s has revealed that about 38% experienced initial symptoms other than memory problems, such as behavior, vision or language problems and a decline in executive function, or the ability to carry out tasks. Of these, 53% were incorrectly diagnosed when first seen by a doctor, compared to 4% of those who had memory problems. Of those with unusual initial symptoms, 47% were still incorrectly diagnosed at the time of their death.

The mean age at onset was 54.5 years (range 46-60). The average duration of the disease was 11 years, with an average diagnostic delay of 3 years.

GPs misidentify and fail to identify early dementia and MCI

A review of 30 studies involving 15,277 people seen in primary care for cognitive disorders, has found that while GPs managed to identify eight out of ten people with moderate to severe dementia, they only identified 45% of those with early dementia and mild cognitive impairment. Moreover, they were very poor at recording such diagnoses. Thus, though they recognized 45% of the MCI cases, they only recorded 11% of these cases in their medical notes. Although they identified 73% of people with dementia, they made correct annotations in medical records in only 38% of cases.

But the problem is not simply one of failing to diagnose — they were even more likely to misidentify dementia, and this was particularly true for those with depression or hearing problems.

The findings point to the need for more widespread use of simple cognitive screening tests.

Prevalence of dementia & MCI in 'oldest old' women

Data from 1,299 women enrolled in the Women Cognitive Impairment Study of Exceptional Aging suggests that the incidence of dementia almost doubles with every 5 years of age and prevalence rises from approximately 2-3% in those 65 to 75 years to 35% in those 85+.

Among those with mild cognitive impairment, amnestic multiple domain was most common (34%), followed by non-amnestic single domain (29%). Amnestic single domain (affecting only one type of cognitive function, including memory difficulty) affected 22%.

Alzheimer's disease and mixed dementia accounted for nearly 80% of dementia cases, and vascular dementia for 12.1%.

Those with dementia tended to be older, less likely to have completed high school, more likely to have reported depression, a history of stroke, and to have the APOEe4 gene.

The women in the study had an average age of 88.2 years and 27% were older than 90. 41% had clinical cognitive impairment (17.8% with dementia and 23.2% with mild cognitive impairment).

The high prevalence of cognitive impairment in this age group points to the importance of screening for cognitive disorders, particularly among high-risk groups.

For the first time in 27 years, clinical diagnostic criteria for Alzheimer's disease dementia have been revised, and research guidelines updated. They mark a major change in how experts think about and study Alzheimer's disease.

The updated guidelines now cover three distinct stages of Alzheimer's disease:

• Preclinical – is currently relevant only for research. It describes the use of biomarkers that may precede the development of Alzheimer’s.
• Mild Cognitive Impairment– Current biomarkers include elevated levels of tau or decreased levels of beta-amyloid in the cerebrospinal fluid, reduced glucose uptake in the brain, and atrophy of certain brain regions. Primarily for researchers, these may be used in specialized clinical settings.
• Alzheimer's Dementia – Criteria outline ways clinicians should approach evaluating causes and progression of cognitive decline, and expand the concept of Alzheimer's dementia beyond memory loss to other aspects of cognition, such as word-finding, vision/spatial issues, and impaired reasoning or judgment.

The criteria are available at http://www.alzheimersanddementia.org/content/ncg

A study following 837 people with MCI, of whom 414 (49.5%) had at least one vascular risk factor, has found that those with risk factors such as high blood pressure, diabetes, cerebrovascular disease and high cholesterol were twice as likely to develop Alzheimer's disease. Over five years, 52% of those with risk factors developed Alzheimer's, compared to 36% of those with no risk factors In total, 298 people (35.6%) developed Alzheimer's.

However, of those with vascular risk factors, those receiving full treatment for their vascular problems were 39% less likely to develop Alzheimer's disease than those receiving no treatment, and those receiving some treatments were 26% less likely to develop the disease.

Treatment of risk factors included using high blood pressure medicines, insulin, cholesterol-lowering drugs and diet control. Smoking and drinking were considered treated if the person stopped smoking or drinking at the start of the study.

A training program designed to help older adults with MCI develop memory strategies has found that their brains were still sufficiently flexible to learn new ways to compensate for impairment in some brain regions. The study involved 30 older adults, of whom 15 had MCI. Participants’ brains were scanned 6 weeks prior to memory training, one week prior to training and one week after training.

Before training, those with MCI showed less activity in brain regions associated with memory. After training they showed increased activation in these areas as well as in areas associated with language processing, spatial and object memory and skill learning. In particular, new activity in the right inferior parietal gyrus was associated with improvement on a memory task.

The findings demonstrate that even once diagnosed with MCI (a precursor to Alzheimer’s disease), brains can still be ‘rewired’ to use undamaged brain regions for tasks customarily done by now-damaged regions.