Ongoing studies in the Division address a wide range of problems including:
Vascular Dementia (VaD) and its relationship to Alzheimer’s disease (AD): While both disorders affect executive function, VaD may go undetected by traditional screening tests. The use of ECF measures, like the CLOX and the EXIT25, may greatly improve our ability to detect VaD.
Conversely, VaD is mixed with AD pathology in a sizable fraction of “AD” cases. Unlike true AD, mixed cases may progress more slowly, respond better to treatment, and might be preventable by interventions directed against their vascular component. Identifying mixed cases and distinguishing them from pure AD is a high priority.
Mild Cognitive Impairment (MCI):
AD pathology begins decades before dementia can be diagnosed. Interventions that delay conversion to dementia, even by a few years, could significantly reduce the number of dementia cases we face as the population ages. “MCI” describes mild cognitive impairments that increase the risk of future dementia. Unfortunately, there is no consensus regarding how to diagnose MCI. Some cases do not progress to dementia, some improve, and some present with non-AD conditions instead. We are studying how ECF measures might be used to improve our ability to distinguish preclinical AD from other conditions, in order to select patients for disease specific interventions.
Cognitive decline is actually expected during normal aging. However, these declines may disproportionately affect executive function, and must be distinguished from pre-clinical AD (MCI) and other conditions. Moreover, because ECF impairments are disabling, the executive impairments of normal aging can be debilitating, even if they are not related to a particular disease.
We are studying normal aging in a cohort of high functioning “Super Seniors” from the Air Force Villages, a major San Antonio Comprehensive Care Retirement Community (CCRC). Our previous work has identified ECF impairment as a major determinant of functional status, level of care and decision making capacity, even in the absence of diagnosable dementia. We are now working with collaborators in the Audie L. Murphy Memorial Veterans Administration Hospital (ALMVAH) Geriatric Education and Clinical Center (GRECC), the Research Imaging Center (RIC), the University of Texas at San Antonio (UTSA), and the Barshop Aging Research Center (BARC) to determine the mechanisms by which age affects executive control.
Treatments for Executive Function: While dementia research has historically focused on memory loss, the loss of executive skills has received relatively little attention. Moreover, memory may have little effect on functional status and decision making capacity independently of ECF impairment. We are exploring treatment strategies that may improve ECF. If successful, such treatments promise to improve functional status and could positively affect the level of care and supervision required by disabled elderly persons. Moreover, such treatments may have applications outside of dementia. Major depression, normal aging, and many medical disorders adversely affect ECF and functional outcomes. Successful interventions against ECF may improve functional status in these conditions as well.
Decision Making Capacity:
Executive functions are important to many instrumental activities of daily living (IADL) like financial capacity, driving, cooking, and successful medication management. ECF measures like CLOX and the EXIT25 have the potential to provide brief, reliable and valid assessment of these abilities. Interventions against executive impairments have the potential to improve IADL’s and may impact autonomy and the capacity for independent living.
ECF impairment is common in many medical disorders. However, in the absence of ECF specific screening, it may not be well detected. We have shown that large fractions of elderly medical patients have executive impairment, although it is seldom detected by their families or their physicians, who often ascribe it to depression, fatigue, or “laziness” instead. Some of this ECF impairment is disease specific, but some may also be an iatrogenic side-effect of commonly used medications or surgical procedures. ECF impairments are debilitating, regardless of their cause, and can affect decision-making capacity, the ability to manage medications, patient self-care, and navigation within the complex healthcare system. ECF testing may help identify medical patients in need of support. Effective treatment could improve patient outcomes in a wide variety of conditions.
We recently studied the effects of cognitive impairment on survival in the AFV. One surprising finding was that mortality was not related to ECF. Instead, simple drawing tasks best predicted survival. We have replicated this finding in several other cohorts.
This observation led us to investigate disorders that affect the right hemisphere, which is important to drawing skills. Survival is worse in AD, stroke, and epilepsy when they affect the right hemisphere. One possible explanation for this may be disruption of the brain’s control of cardiac function. Only a few brain regions are likely to play a role in this, particularly the insular cortex. The insula is involved in autonomic responses, particularly cardiac responses to pain, emotion, and stress. It is also vulnerable to stroke, AD, LBD and epilepsy. AD affects the insula before the onset of dementia. Thus, falls, dizziness, and even sudden death in non-demented persons may yet be caused by AD pathology. Similarly, autonomic changes and cardiac rhythm disturbances may help distinguish pre-clinical AD from other causes of MCI. Depression is associated with both increased mortality and insular dysfunction. We are investigating whether preclinical AD pathology explains the association between depressive symptoms and mortality in older adults.
In addition, Dr. Royall’s research group conducts clinical trails of novel agents for the treatment of AD and related cognitive disorders. Newer agents may have the capacity to delay the onset of Alzheimer’s dementia, or modify its progress. In addition, Dr. Royall is exploring treatments for executive impairment. These may be relevant to a variety of conditions including normal aging.