Mario Masellis, MSc, MD, FRCPC, Clinical Associate & Research Fellow, L.C. Campbell Cognitive Neurology Research Unit, Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON.
Sandra E. Black, MD, FRCPC, Brill Professor of Neurology, L.C. Campbell Cognitive Neurology Research Unit, Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON.

Cognitive impairment occurs along a continuum from mild subjective memory complaints occurring during the normal aging process to severe memory and other cognitive deficits due to dementia, the most common subtype being mixed Alzheimer’s disease and vascular dementia. Due to the significant growth of the older adult population, the incidence of dementia is on the rise and is posing significant challenges for health care systems worldwide. Primary care practitioners are on the front lines of this battle against dementia and will play an increasingly important role in the early identification of disease. Cognitive screening tests are helpful in detecting people in the early stages of dementia and facilitate further clinical and diagnostic evaluations. Primary care practitioners should aggressively treat known cardiovascular risk factors for dementia and institute early symptomatic therapy when appropriate.
Key words: dementia, cognitive screening test, cognitive reserve, neuroimaging, biomarkers.

An Overview of the Last Day of the 10th Annual Rotman Institute Conference

Nadège Chéry, PhD

Among the events that alter normal brain function, aging is an important factor. Neuroimaging is one of the methods used by clinicians/ researchers to assess the neural changes in older adults. Using positron emission tomography (PET) scanning, neuroscientists have discovered that the frontal lobes (the theme of the Rotman Research Institute Conference) are the areas of the brain that are more active when older individuals perform cognitive tasks. With this approach, they have identified new cognitive pathways in the frontal lobes that may enable the elderly to perform as well as younger adults.

Using positron emission tomography (PET) scanning, neuroscientists have discovered that the frontal lobes are the areas of the brain that are more active when older individuals perform cognitive tasks.

Dr. Cheryl L. Grady, a scientist at the Rotman Research Institute who also holds appointments at the University of Toronto, used PET scanning to study frontal lobe activity in old individuals (age 60 and up) while they performed the same cognitive tasks as younger adults (in their 20s).

In particular, she studied the age-related changes in episodic memory (which is defined as the conscious recollection of events that have occurred in a person's experience), as opposed to semantic or working memory.

The participants were subjected to various episodic paradigms (verbal and non-verbal). Interestingly, the individuals remembered pictures better than they remembered words, regardless of their age (these observations accord with other studies). This phenomenon is referred to as "the picture superiority effect", explained Dr. Steven E. Petersen, professor at the Department of Neurology, Washington University, in St-Louis. He also indicated that one of the mechanisms underlying this effect may be the strong activation of the right prefrontal cortex (right frontal lobes), as observed in human PET scans during picture recognition tasks.

Dr. Grady's goal was to examine the correlation between brain activity patterns and the performance of cognitive tasks. In one of her experiments, a series of faces were presented to the young and old subjects, who were later scanned while they were shown previously-seen faces, along with new faces. When asked to identify the faces seen earlier, the older adults had a reduced performance compared to the younger adults (66% vs. 80% correct). The PET scans indicated that both groups showed activation of the right prefrontal cortex (PFC), but this activation was smaller in older adults. Thus, this may account for their reduced success rate in face recognition.

However, in another cognitive test, the subjects were scanned during episodic encoding and retrieval of word pairs. Here is how the experiment worked: At an earlier stage, a series of word pairs were presented to the individuals. They had to learn these pairs and make some association between the words in each pair. Later, the first word in a pair was shown to the subjects and their task was to recall the second word. The results were quite interesting.

First, during the encoding, the elderly showed a reduced activity in the left prefrontal and temporal cortex compared to the activity in younger participants. However, the performance of young and old adults was similar during the retrieval process. Both young and old subjects showed an increased activation in the right PFC, yet this activation appeared reduced in the elderly. How, then, could they retrieve the words as well as the younger subjects?

Dr. Grady concluded that older adults seem to be utilizing their left PFC more, and that this may represent a compensatory process in the elderly which allows them to maintain cognitive functions.

Closer inspection of the scans indicated an additional activity in the left PFC of the older adults (an area that is not normally activated in younger brains during the retrieval process). "You can get this left prefrontal [activity] increase even when the older person is not performing as well as the young adult", said Dr. Grady. These findings show that the type of stimulation that is encoded (pictures vs. words) is a critical component in the age-related alterations in brain areas involved in memory work. Dr. Grady concluded that older adults seem to be utilizing their left PFC more, and that this may represent a compensatory process in the elderly which allows them to maintain cognitive functions. She admitted, however, that the precise role of the PFC in these cognitive functions remains to be investigated.

Different hypotheses on the role of the PFC in cognitive functions have been stated. Some are on the subject of the regulation of PFC neurons by specific neurochemical transmitters. According to Dr. Todd S. Braver, another speaker at the Conference and assistant-professor in the Department of Psychology, Washington University in St-Louis, "the dopamine neurotransmitter system may serve to regulate PFC activity, by "gating" the access of context information into active memory through simple modulatory effects".

Such neuronal modulations/ changes are also indicative of a certain plasticity that may occur in the frontal lobes of the aged person. Thus, activity in cortical regions beyond (or around) the deficient areas may "come to the rescue" when the latter are solicited in cognitive tasks. However, "plasticity may be limited," explained Dr. Brian E. Kolb, professor at the Department of Psychology and Neuroscience, University of Lethbridge in Alberta: "When plasticity has occurred in the cortex, it may limit its ability for subsequent plasticity."

In conclusion, the studies presented at the Rotman Conference showed that neuroimaging is a useful tool for understanding cognitive functions. According to Dr. Petersen, neuroimaging may also allow us to understand the possible mechanisms of recovery from brain injury. Indeed, Dr. Petersen described the remarkable performance of a patient suffering from a left frontal injury, during a word stem completion task. For example, when presented with the stem COU, the patient had to say COUSIN. That patient was 85&endash;90% correct in this cognitive exercise, which normally requires functional left frontal lobes (left hemisphere lesions usually result in language/speech difficulty). How could a patient with left frontal lobe injury perform so well in such a test? When he was PET scanned, an increased activation was found in his right hemisphere. And interestingly, this was not an isolated case, for other patients with left frontal lobe injury, enhanced activity in the right hemisphere could also be observed.

Thus, different possible neural substrates can be used in recovery processes. This may lead to the use of different therapeutic strategies in the treatment of neurobiologically-based diseases.