Not too long ago, doctors trying to diagnose neurological disorders like Alzheimer's and Parkinson's could only rely on external symptoms and batteries of cognitive tests.
Without a peephole to the brain, only an autopsy could confirm what was actually happening to the structures inside the skull.
Four decades of increasingly sophisticated imaging techniques have given physicians and researchers many tools to get real-time looks at what's happening -- or not -- in the brain.
But scientists are still working to match brain-scan images with understanding of what's normal for a certain age and what's worrisome in each region of the brain, along with figuring out how connections between different regions behave.
One recent study conducted at Northwestern University in Chicago used three-dimensional magnetic resonance imaging to detect differences in the brains of so-called SuperAgers: people 80-plus whose memories are as sharp as those 20 or 30 years younger.
Researchers led by Emily Rogalski, an assistant research professor at Northwestern's Cognitive Neurology and Alzheimer's disease Center, did scans and memory tests on 12 people identified as having exceptional memory, as well as 10 elderly 80-somethings with average memory and 14 volunteers aged 50 to 65.
What was most striking about the brains of the super-sharp seniors? Each had a thick cortex, the outer layer of gray matter that's important for memory, attention and cognition. The layer was much thicker than seen in the group of normal-aging elders, and closely matched the cortex size of the younger people.
Imaging also showed another region deep in the brain -- the anterior cingulate cortex -- was thicker in the SuperAgers than in the 50- to 65-year-olds. The region is important to attention and motivation, which may be why the SuperAgers have exceptional memories, Rogalski said.
The research on healthy aging brains, published in August's Journal of the International Neuropsychological Society, could eventually be used to help protect the elderly from memory loss or even Alzheimer's disease, the researchers said.
At the other end of the age spectrum, a study published in the journal Current Biology online in mid-August described how scientists have mapped a "developmental clock" to assess brain maturity from ages 3 to 20.
Led by Tim Brown at the University of California at San Diego's School of Medicine, they used 231 anatomical markers visible through MRI scans to assess age, give or take a year, with 92 percent accuracy. Earlier research had suggested much greater variation in the maturing of different brain structures in youth.
The study, which also involved scientists from nine other universities, analyzed brain scans from 885 typical children and teens to draft a scale based on features such as thickness and size of the cortex, the volume of deep brain structures, tissue properties and the intensity of brain signals.
Brown said while more work needs to be done to make the scale useful in clinical care, the consistent pace of brain maturity suggests the growth milestones could be used for early detection of developmental brain disorders.
Another group of UCSD researchers has taken a different approach to identifying neural disease, using the eyes as a window to the brain, if not the soul.
They've developed several new fluorescent probes that change color depending on the type of sticky protein plaques, or amyloids, they encounter. Different amyloids are found in the brains of patients with Creutzfeldt-Jakob disease as opposed to Alzheimer's.
Current brain scans can use radioactive tracers to spot amyloid but can't specify which type of proteins is present. However, amyloid also accumulates in the eyes.
The researchers reported, in the Journal of the American Chemical Society published online in mid-August, that one of their probes glows yellow when it hits amyloids associated with prions found in CJD, but green when it binds with proteins linked to Alzheimer's.
The team is working to develop additional probes for different diseases, but the technology has already been licensed for commercial development in diagnostic tests.