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Harvard Team Finds Key Cause of Age-Related Brain Fog

Decline of aging brains linked to loss of "white matter" channels that transmit internal cross-talk; omega-3s build the neuronal networks central to healthy white matter
by Craig Weatherby

A steady stream of studies published over the past few years has highlighted the role that omega-3s play in enabling and enhancing brain structures and functions essential to optimal mental performance.

For example, animal and cell experiments show that omega-3s
especially DHAstimulate changes that promote stronger and more numerous networks between the brain's nerve cells (neurons), which occur at the neuron-connecting points called synapses:
Key Points
  • Decline of conduits between brain regions may underlie age-related loss of mental acuity.
  • Finding highlights importance of brain's “white matter” channels to sharp thinking and memory.
  • Omega-3s promote the healthy neuronal connections needed to build white matter, with implications for healthier aging and future research.
  • Increased formation of synaptic membranes.
  • Higher levels of important proteins within synaptic membranes.
  • Increases in the small outgrowths of neuronal cell membranes called neurites.
For more on these points, see “New Insight into Anti-Aging Brain Benefits of Omega-3s” and “MIT Report Shows Omega-3s Boost Brain Networks Critical to Memory Capacity.”

Recent studies reveal continuous increases in the amount of neuron-rich “white matter” throughout adolescence, accompanied by increasingly better performance in tests of decision-making power and speed.

(See “Omega-3s Seen Boosting Performance of Healthy Young Brains.”)

And a new discovery about the importance of white matter to maintaining brain function as we age suggests avenues of research, including the supportive potential of omega-3s.

Why white matter matters
The human brain contains several major functional regions, each responsible for different tasks, such as memory, sensory processing, and decision-making.

Scientists have known that white matter degrades with age, but they did not understand how that decline contributes to declines in thinking and memory.

These functional regions are connected by conduits consisting of white matter, which enable the various regions to coordinate activity and share information.

In young, healthy brains, signals are readily transmitted by white-matter conduits. As we age, those conduits decline. Depending on the networks involved, the result could be impaired memory, reasoning or other advanced cognitive functions.

Harvard team finds inter-regional communication key to healthy brain function

According to Jessica Andrews-Hanna, lead author of the new study by Harvard University's Howard Hughes Medical Institute, “The crosstalk between the different parts of the brain is like a conference call. We were eavesdropping on this crosstalk and we looked at how activity in one region of the brain correlates with another” (HHMI 2007).

The Harvard researchers tested brain function in a group of volunteers aged from 18 to 93. Of these, the 38 volunteers aged 18-34 were classified as “young adults” and the 55 aged 60-93 were designated “old adults.”

They analyzed brain function using functional magnetic resonance imaging (fMRI), which measures blood flow throughout the brain in order to show areas of mental activity.

Using an MRI technique called diffusion tensor imaging, the Harvard team looked at links within two critical networks: one responsible for processing information from the outside world and one that is more internal.

The new study revealed a dramatic difference in these regions between young and old subjects.

As the researchers said, “We found that in young adults, the front of the brain was pretty well in sync with the back of the brain. In older adults this was not the case. The regions became out of sync and they were less correlated with each other” (HHMI 2007).

Confirming the importance of these connections, the older adults with normal, high correlations performed better on cognitive tests.

This analysis revealed that the reduced functional connection they detected in brain areas of the older subjects reflected decreased white matter.

Significantly, they found that the subjects who showed the lowest functional correlation between brain regions also had the lowest cognition-test scores.

Note: While loss of white matter impairs brain performance in people with normal age-related cognitive decline (ARCD) and in Alzheimer's patients, the two types of dementia are characterized by distinctly different disruptions in intra-brain communication. These distinctions may explain the differences in severity and progression of standard ARCD and Alzheimer's disease.

Practical implications of the findings
It remains to be seen whether any given person's ability to maintain the integrity of their white matter conduits is affected by diet, exercise or other lifestyle factors, or is dominated by genetic influences.

Thus, any lifestyle or food factor that supports optimal growth of neurons and the synaptic connections between them is highly desirable.

Other changes in the aging brain
such as cells' decreased ability to produce chemical neurotransmittersmay also contribute to cognitive decline.

Interestingly, animal and human experiments show that omega-3s are important to the production of serotonin: a key neurotransmitter associated with healthy mood, among other things (Hibbeln JR et al 1998).

Given what we already know about the role of omega-3s in promoting neuron growth and connections, and production of key neurotransmitters, it seems a safe bet that they help maintain brain function as we age.

  • Andrews-Hanna JR, Snyder AZ, Vincent JL, Lustig C, Head D, Raichle ME, Buckner RL. Disruption of large-scale brain systems in advanced aging. Neuron. 2007 Dec 6;56(5):924-35.
  • DeCarli C, Grady CL, Clark CM, Katz DA, Brady DR, Murphy DG, Haxby JV, Salerno JA, Gillette JA, Gonzalez-Aviles A, Rapoport SI. Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter. J Neurol Neurosurg Psychiatry. 1996 Feb;60(2):158-67.
  • Liddell BJ, Paul RH, Arns M, Gordon N, Kukla M, Rowe D, Cooper N, Moyle J, Williams LM. Rates of decline distinguish Alzheimer's disease and mild cognitive impairment relative to normal aging: integrating cognition and brain function. J Integr Neurosci. 2007 Mar;6(1):141-74.
  • Hibbeln JR, Umhau JC, Linnoila M, George DT, Ragan PW, Shoaf SE, Vaughan MR, Rawlings R, Salem N Jr. A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids. Biol Psychiatry. 1998 Aug 15;44(4):243-9.
  • Hibbeln JR, Linnoila M, Umhau JC, Rawlings R, George DT, Salem N Jr. Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biol Psychiatry. 1998 Aug 15;44(4):235-42.
  • Howard Hughes Medical Institute (HHMI) The Aging Brain: Failure to Communicate. Accessed online December 6, 2007 at