Scientists have found a compelling clue in the quest to learn what causes age-related memory problems, and to one day be able to tell if those misplaced car keys are just a senior moment or an early warning of something worse.
Wednesday's report offers evidence that age-related memory loss really is a distinct condition from pre-Alzheimer's — and offers a hint that what we now consider the normal forgetfulness of old age might eventually be treatable.
Researchers at Columbia University Medical Center examined brains, young and old ones, donated from people who died without signs of neurologic disease. They discovered that a certain gene in a specific part of the hippocampus, the brain's memory center, quits working properly in older people. It produces less of a key protein.
That section of the brain, called the dentate gyrus, has long been suspected of being especially vulnerable to aging. Importantly, it's a different neural neighborhood than where Alzheimer's begins to form.
But it's circumstantial evidence that having less of that protein, named RbAp48, affects memory loss in older adults. So the researchers took a closer look at mice, which become forgetful as they age in much the same way that people do.
Sure enough, cutting levels of the protein made healthy young rodents lose their way in mazes and perform worse on other memory tasks just like old mice naturally do.
More intriguing, the memory loss was reversible: Boosting the protein made forgetful old mice as sharp as the youngsters again, the researchers reported in the journal Science Translational Medicine.
"It's the best evidence so far" that age-related memory loss isn't the same as early Alzheimer's, said Nobel laureate Dr. Eric Kandel, who led the Columbia University team.
And since some people make it to 100 without showing much of a cognitive slowdown, the work begs another question: "Is that normal aging, or is it a deterioration that we're allowing to occur?" Kandel said.
"As we want to live longer and stay engaged in a cognitively complex world, I think even mild age-related memory decline is meaningful," added Columbia neurologist Dr. Scott Small, a senior author of the study. "It opens up a whole avenue of investigation to now try to identify interventions."
This is early-stage research that will require years of additional work to confirm, cautioned Dr. Molly Wagster of the National Institute on Aging, who wasn't involved with the report.
But Wagster said the findings add to a growing body of evidence suggesting "that we're not all on the road to Alzheimer's disease" after we pass a certain age.
For example, other researchers have found that connections between neurons in other parts of the brain weaken with normal aging, making it harder but not impossible to retrieve memories. In contrast, Alzheimer's kills neurons.
How does Wednesday's research fit? Many pathways make up a smoothly functioning memory, and that protein plays a role in turning a short-term memory — like where you left those car keys — into a longer-term one, Kandel explained.
Some good news: Scientists already know that exercise makes the dentate gyrus — that age-targeted spot in the hippocampus — function better, Small said. He's also studying if nutrition might make a difference.
Exercise is touted as helping healthy adults stay that way, both physically and mentally. Might it also help people whose memory and other cognitive abilities have started to decline?
This study included 35 adults who averaged in their mid- to upper 70s; they consisted of two groups: 18 with mild cognitive impairment and 17 with no cognitive decline. Everyone did moderate exercise, walking on a treadmill with increasing frequency and duration until they were doing four 30-minute sessions a week. After 12 weeks, both groups registered about a 10 percent improvement in cardio-respiratory fitness. Brain scans and a battery of standardized neuropsychological tests, focusing on memory, showed cognitive improvement in both groups, and to virtually the same degree, including such aspects as better recall and improved neural efficiency (less brainpower required for cognitive tasks). The researchers noted that, in people with mild cognitive impairment, treatment that achieves stability in memory is considered successful; they described the cognitive improvement in their impaired participants as “remarkable.”
Higher variability in visit-to-visit blood pressure readings, independent of average blood pressure, could be related to impaired cognitive function in old age in those already at high risk of cardiovascular disease, suggests a paper published today on bmj.com.
There is increasing evidence that vascular factors contribute in development and progression of dementia. This is of special interest as cardiovascular factors may be amendable and thus potential targets to reduce cognitive decline and the incidence of dementia. Visit-to-visit blood pressure variability has been linked to cerebrovascular damage (relating to the brain and its blood vessels). It has also been shown that this variability can increase the risk of stroke.
It has been suggested that higher blood pressure variability might potentially lead to cognitive impairment through changes in the brain structures.
Researchers from the Leiden University Medical Center (Netherlands), University College Cork (Ireland) and the Glasgow University (UK) therefore investigated the association of visit-to-visit blood pressure variability (independent of average blood pressure) with cognitive function in older subjects at high risk of cardiovascular disease.
All data were obtained from the PROSPER study, which investigated the effect of statins in prevention of vascular events in older men and women. This study took data on 5,461 individuals aged 70-82 years old in Ireland, Scotland and the Netherlands. Average follow-up was three years.
Both systolic (peak pressure) and diastolic (minimum pressure) blood pressures were measured every three months in the same clinical setting. The variability between these measurements were calculated and used in the analyses.
The study used data on cognitive function where the following was tested: selective attention and reaction time; general cognitive speed; immediate and delayed memory performance.
Results showed that visit-to-visit blood pressure variability was associated with worse performance on all cognitive tests. The results were consistent after adjusting for cardiovascular disease and other risk factors.
The main findings of the study were: higher visit-to-visit blood pressure variability is associated with worse performance in different cognitive tests; higher variability is associated with higher risk of stroke and both these associations are independent of various cardiovascular risk factors, in particular, average blood pressure.
Researcher Simon Mooijaart, (Leiden University Medical Centre, Leiden, the Netherlands) says that by using a population of "over five thousand participants and over three years of blood pressure measurements, we showed that high visit-to-visit systolic and diastolic blood pressure variability associates with worse performance in different domains of cognitive function including selection attention, processing speed, immediate verbal memory and delayed verbal memory". The researchers do add though that it is still unclear whether higher blood pressure variability is a cause or consequence of impaired cognitive function.
They suggest several explanations for their findings: firstly that blood pressure variability and cognitive impairment could stem from a common cause, with cardiovascular risk factors being the most likely candidate; secondly that variability might reflect a long term instability in the regulation of blood pressure and blood flow to the key organs in the body; thirdly that exaggerated fluctuations in blood pressure could result in the brain not receiving enough blood, which can cause brain injury, leading to impairment of cognitive function.
The researchers conclude that "higher visit-to-visit blood pressure variability independent of average blood pressure might be a potential risk factor with worse cognitive performance in older subjects at high risk of cardiovascular disease". Given that dementia is a major public health issue, they say that further interventional studies are warranted to establish whether reducing blood pressure variability can decrease the risk of cognitive impairment in old age.