The ratio of two amyloid-β (Aβ) peptides in plasma may prove to be a useful biomarker for the preclinical diagnosis of dementia and Alzheimer’s disease, a meta-analysis suggested.
Pooled analysis of six studies found increased risk for dementia in general among individuals with the lowest Aβ42 to Aβ40 ratio (RR 1.67, 95% CI 1.02 to 2.75, P=0.04), according to Alain Koyama, SM, of the University of California San Francisco, and colleagues.
Moreover, in six studies, an elevated risk specifically for Alzheimer’s disease also was seen for those with the lowest Aβ42 to Aβ40 ratio (RR 1.60, 95% CI 1.04 to 2.46, P=0.03), the researchers reported online in the Archives of Neurology.
“The existing research offers cautious support of the hypothesis that lower levels of the plasma Aβ42 to Aβ40 ratio reflect a process of selective deposition of Aβ42 in the brain as insoluble amyloid plaques, thus predictive of dementia development,” they stated.
However, there was significant heterogeneity among the studies included, with an I2 statistic of 80% for the Aβ42 to Aβ40 ratio and 64% for Aβ42 alone.
“Thus, the summary RRs must be interpreted cautiously,” Koyama and colleagues warned.
This meta-analysis found that lower values of the ratio of plasma amyloid-β42 to Aβ40 was associated with development of dementia and Alzheimer’s disease.
Note that the evaluated studies had considerable heterogeneity and neither marker alone was predictive, but the authors urged further study since a simple blood test has appeal as a preclinical diagnostic tool.
With an annual price tag of $172 billion, dementia in its various forms is now commanding much research attention, with the goal of identifying ways of making the diagnosis early, when interventions are most likely to successfully ward off cognitive decline.
Dementia has early warning signs and symptoms. An early diagnosis will help manage a person’s dementia. Signs may be vague but may include loss of memory, particularly for recent events, confusion, apathy, withdrawal and the loss of ability to do everyday tasks. Other conditions have symptoms similar to dementia.
Possible Early Dementia Overview
Dementia is a serious brain disorder that interferes with a person’s ability to carry out everyday tasks.
– The key feature of dementia is a decline in cognitive functions. These are mental processes such as thinking, reasoning, learning, problem solving, memory, language, and speech.
– Other features that occur frequently in dementia include changes in personality and behavior.
– Generally, these symptoms are not considered dementia unless they have continued unabated for at least 6 months.
– Dementia has many different causes. Some may be reversible, such as certain infections, drug intoxication, and liver diseases. Of the irreversible causes, the most common in older adults is Alzheimer’s disease.
– Although dementia is frequently linked to old age (“getting senile”), it is not a normal part of aging. Even children with certain degenerative brain disorders can develop dementia.
Alzheimer’s disease usually begins with mild, slowly worsening memory loss. Many older people fear that they have Alzheimer’s disease because they can’t find their eyeglasses or remember someone’s name.
– These very common problems are most often due to slowing of mental processes with age. It is not clear whether this is a normal part of aging.
– While this is a nuisance, it does not significantly impair a person’s ability to learn new information, solve problems, or carry out everyday activities, as Alzheimer’s disease does.
– Medical professionals call this benign senescent forgetfulness, age-related memory loss, or mild cognitive impairment (MCI).
Memory loss follows a specific pattern in Alzheimer’s disease. The losses are mainly in short-term memory. This means that the person has problems remembering recent events.
– The person cannot remember what he did last week or instructions the doctor gave this morning for taking a new medicine.
– This often contrasts sharply with the person’s strong ability to remember minor details and events from many years ago.
– The memory loss is followed by many other cognitive and behavioral symptoms. Eventually, over many years, the person loses many mental and physical abilities and requires around-the-clock care.
Plasma levels of the amyloid peptides are one focus of intense interest, and particularly the neurotoxic Aβ42 subgroup, but studies in the literature thus far have had distinct methodologic differences that complicate data interpretation.
In an attempt to provide clarification of the available data, Koyama and colleagues conducted a systematic review and meta-analysis of the literature to date, identifying 13 relevant case-cohort studies that included 10,303 patients.
As with dementia and Alzheimer’s disease, the baseline Aβ42 to Aβ40 ratio also was associated with worse cognitive decline in three studies, with one study indicating that the association was strongest among individuals with low levels of education.
Six studies assessed the risk of dementia according to Aβ42 levels alone, with two showing a significant association with lower levels.
However, the pooled analysis for this marker was not significant (RR 1.37, 95% CI 0.95 to 1.98, P=0.10).
Studies looking at risk of Alzheimer’s disease according to Aβ42 levels alone had inconsistent results, and the pooled analysis showed no association (RR 1.01, 95% CI 0.48 to 2.11, P=0.99).
Nor was there a significant association with Alzheimer’s disease for plasma levels of Aβ40 alone (RR 1.66, 95% CI 0.98 to 2.83, P=0.06).
Ten warning signs
1.Recent memory loss that affects day to day functions
It is normal to forget meetings, colleagues’ names or a friend’s telephone number occasionally, but then remember them later. A person with dementia may forget things more often, and not remember them at all.
2. Difficulty performing familiar tasks
Busy people can be so distracted from time to time that they may leave the carrots on the stove and only remember to serve them when the meal has finished. A person with dementia might prepare a meal and not only forget to serve it, but also forget they made it.
3. Problems with language
Everyone has trouble finding the right word sometimes, but a person with dementia may forget simple words or substitute inappropriate words, making sentences difficult to understand.
4. Disorientation to time and place
It is normal to forget the day of the week or your destination for a moment. But people with dementia can become lost on their own street, not knowing where they are, how they got there or how to get back home.
5. Poor or decreased judgement
Dementia affects a person’s memory and concentration, and this in turn affects their judgement. Many activities, such as driving, require good judgement and when this ability is affected, the person will be a risk, not only to themselves, but also to others on the road.
6. Problems with abstract thinking
Balancing a cheque book may be difficult for many of us. Someone with dementia could forget completely what the numbers are and what needs to be done with them.
7. Misplacing things
Anyone can temporarily misplace a wallet or keys. A person with dementia may repeatedly put things in inappropriate places.
8. Changes in mood or behaviour
Everyone becomes sad or moody from time to time. Someone with dementia can have rapid mood swings, for no apparent reason. They can become confused, suspicious or withdrawn.
9. Changes in personality
People’s personalities can change a little with age. But a person with dementia can become suspicious or fearful, or apathetic and uncommunicative. They may also become dis-inhibited, overfamiliar or more outgoing than previously.
10. Loss of initiative
It is normal to tire of housework, business activities or social obligations. The person with dementia may lose interest in previously enjoyed activities, or become very passive and require cues prompting them to become involved.
Based on Is it Alzheimer’s? Ten Warning Signs You Should Know, Alzheimer’s Association, USA
Potential explanations for the significant heterogeneity seen in the analysis included different ways of measuring the peptides, with some studies using multiplex platforms and others using enzyme-linked immunosorbent assays.
“Therefore, the development of a standardized assay is highly important to achieve more comparable results in further research on plasma Aβ,” the researchers wrote.
They noted that future studies also should include data on baseline cognition, which was lacking in most of the current studies, and should assess changes of Aβ levels over time.
The individual studies also may have been influenced by confounding or bias, and the analysis included no details on diagnostic accuracy such as sensitivity or specificity.
Nonetheless, the authors noted that “plasma Aβ is a particularly appealing biomarker” because deposition of this group of peptides is thought to be an initiating factor in Alzheimer’s disease, and a noninvasive test could be done easily and inexpensively.
Further research is therefore warranted, they concluded.
The study was funded by the National Institutes of Health.
One co-author is a director of Elan.
Primary source: Archives of Neurology
Source reference: Koyama A, et al “Plasma amyloid-β as a predictor of dementia and cognitive decline: a systematic review and meta-analysis” Arch Neurol 2012; DOI: 10.1001/archneurol.2011.1841.