Alzheimer’s biomarkers present decades before symptoms

July, 2012
  • People with a strong genetic risk of early-onset Alzheimer’s have revealed a progression of brain changes that begin 25 years before symptoms are evident.

A study involving those with a strong genetic risk of developing Alzheimer’s has found that the first signs of the disease can be detected 25 years before symptoms are evident. Whether this is also true of those who develop the disease without having such a strong genetic predisposition is not yet known.

The study involved 128 individuals with a 50% chance of inheriting one of three mutations that are certain to cause Alzheimer’s, often at an unusually young age. On the basis of participants’ parents’ medical history, an estimate of age of onset was calculated.

The first observable brain marker was a drop in cerebrospinal fluid levels of amyloid-beta proteins, and this could be detected 25 years before the anticipated age of onset. Amyloid plaques in the precuneus became visible on brain scans 15-20 years before memory problems become apparent; elevated cerebrospinal fluid levels of the tau protein 10-15 years, and brain atrophy in the hippocampus 15 years. Ten years before symptoms, the precuneus showed reduced use of glucose, and slight impairments in episodic memory (as measured in the delayed-recall part of the Wechsler’s Logical Memory subtest) were detectable. Global cognitive impairment (measured by the MMSE and the Clinical Dementia Rating scale) was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset.

Family members without the risky genes showed none of these changes.

The risky genes are PSEN1 (present in 70 participants), PSEN2 (11), and APP (7) — note that together these account for 30-50% of early-onset familial Alzheimer’s, although only 0.5% of Alzheimer’s in general. The ‘Alzheimer’s gene’ APOe4 (which is a risk factor for sporadic, not familial, Alzheimer’s), was no more likely to be present in these carriers (25%) than noncarriers (22%), and there were no gender differences. The average parental age of symptom onset was 46 (note that this pushes back the first biomarker to 21! Can we speculate a connection to noncarriers having significantly more education than carriers — 15 years vs 13.9?).

The results paint a clear picture of how Alzheimer’s progresses, at least in this particular pathway. First come increases in the amyloid-beta protein, followed by amyloid pathology, tau pathology, brain atrophy, and decreased glucose metabolism. Following this biological cascade, cognitive impairment ensues.

The degree to which these findings apply to the far more common sporadic Alzheimer’s is not known, but evidence from other research is consistent with this progression.

It must be noted, however, that the findings are based on cross-sectional data — that is, pieced together from individuals at different ages and stages. A longitudinal study is needed to confirm.

The findings do suggest the importance of targeting the first step in the cascade — the over-production of amyloid-beta — at a very early stage.

Researchers encourage people with a family history of multiple generations of Alzheimer’s diagnosed before age 55 to register at http://www.DIANXR.org/, if they would like to be considered for inclusion in any research.

Reference: 

[2997] Bateman, R. J., Xiong C., Benzinger T. L. S., Fagan A. M., Goate A., Fox N. C., et al.
(2012).  Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease.
New England Journal of Medicine. 120723122607004 - 120723122607004.

Related News

Data from more than 14,265 people older adults (51+) multiple times over a decade or more through the University of Michigan Health and Retirement Study has found that people with higher “multimorbidity scores” showed much faster cognitive decline than those with lower scores, even though most o

Large study shows level of beneficial alcohol consumption much lower than thought

Data from over 5,000 individuals found that a measure of belly fat (waist:hip ratio) was associated with reduced cognitive function in older Irish adults (60+). Body mass index (BMI), however, was found to protect cognitive function.

A study involving 116 healthy older adults (65-75) has found that higher levels of several key nutrients in the blood were associated with more efficient brain connectivity and better cognitive performance.

A long-running study involving 8225 adults found that self-reported diet during midlife (mean age 50) was not significantly associated with subsequent risk for dementia.

A small study comparing 38 younger adults (average age 22) and 39 older adults (average age 68) found that the older adults were less able to recognize when they made errors.

Can computer use, crafts and games slow or prevent age-related memory loss?

Americans with a college education live longer without dementia and Alzheimer's

Socially active 60-year-olds face lower dementia risk

Stressors in middle age linked to cognitive decline in older women

Data from some 900 older adults has linked stressful life experiences among middle-aged women, but not men, to greater memory decline in later life.

Pages

Subscribe to Latest newsSubscribe to Latest newsSubscribe to Latest health newsSubscribe to Latest news
Error | About memory

Error

The website encountered an unexpected error. Please try again later.