Research Grant Recipients 2008-2009

David Vocadlo

The Vocadlo lab has developed molecules that inhibit an enzyme that is implicated in the disease process leading to Alzheimer's disease (AD). We have shown that administering these compounds to animals results in a decrease of harmful protein deposits in the brain that are associated with AD. However, the optimal minimal dose of these inhibitors to reduce these protein deposits has not been determined, which means it is unclear what the minimum safe and effective dose of compound might be to provide a maximum protective effect in human disease.

We plan to administer different doses of one such inhibitor to mice for a short time, in order to determine the differing effects on proteins and enzymes in the brain. This study will provide an estimate of the minimum effective dose required to beneficially affect brain proteins associated with AD pathology without upsetting the balance of important regulatory brain enzymes. Using this information for dose selection, we then plan to administer different amounts of inhibitor to transgenic mice that develop AD-like symptoms. After dosing these mice with inhibitor for several months, we will measure the effects on brain proteins and enzymes, as well as effects on the behaviour of the mice.

Collectively, these studies will allow us to identify the minimal therapeutically effective dose for reducing AD-like symptoms in mice, both at the biochemical and behavioural levels, without inducing potentially detrimental effects. These studies will also provide basic information regarding the interaction between different enzymes in the brain that are involved in AD pathology. This work will directly contribute to the development of this class of inhibitors as a potential treatment for AD. The results from this study will lay the groundwork for clinical testing of these molecules in humans, and may lead to the development of a novel class of disease-modifying Alzheimer's therapies.

Jennifer Marie Barker

Women have an increased risk for developing Alzheimer's disease (AD) compared to men. The disease progresses more rapidly in women, and the onset of AD is generally earlier in women than in men. Hormone replacement therapy (HRT) can decrease the risk for AD and improve cognition (verbal and working memory tasks) in female AD patients. The beneficial effect of HRT on cognition in women, however, depends upon the specific type of HRT (e.g. estrogens with or without progesterone), the source of estrogens administered (e.g. conjugated equine estrogens/estrone vs. estradiol) and the duration of HRT, demonstrating the need for further research in how different combinations of estrogens (E1 and E2) are progesterone affect cognition, health and neuroprotection.

I will investigate the effects of estradiol on cognition and on the generation and survival of new neurons in the brains of young and aged, male and female rodents. Specifically, I will investigate (1) whether new neurons are more responsive to estradiol, in terms of neuron production and synapse formation, at different stages of cell maturation, (2) whether long-term administration of estradiol affects cell survival and synapse formation, and (3) whether the affects of estradiol on new neurons are related to effects on hippocampus-dependent memory. These experiments will be one stage in determining the optimal hormone treatment conditions for improving cognition in cognitively impaired individuals.

Megan Caines

While a great deal of research has been conducted examining the experiences and support needs of caregivers of individuals with Alzheimer's disease and other typical forms of dementia, very little attention has been focused on those that care for individuals with atypical forms of dementia (i.e., Frontotemporal dementia, Huntington's disease, etc.). These dementias, unlike typical dementias, are often marked by personality and behavioural changes in their early stages, rather than by memory difficulties.

Some researchers have suggested that caregivers of individuals with Frontotemporal dementia (FTD) may face challenges beyond those faced by typical dementia caregivers. Specifically, unique challenges for these caregivers have been identified relating to the nature of FTD symptomatology, the misdiagnoses and/or delays in diagnosis that frequently occur in cases of FTD, the lack of information currently available on FTD, and the early age of onset of this disease. It is conceivable that these challenges would also be relevant to other groups of atypical dementia caregivers as well, particularly to the extent that the atypical dementia type diverges from the common conception of dementia (i.e., old, memory difficulties, etc.).

Lending support to the idea that atypical caregivers face challenges unique to their role, two studies to date have actually compared the experiences of atypical and typical dementia caregivers, finding that atypical dementia caregivers were more burdened by their caregiving role and more distressed by their care-recipients symptomatology. Importantly, the findings from both of these studies highlight the need to distinguish between diagnostic groups of dementia when discussing caregiver issues. Furthermore, they emphasize the importance of providing support to atypical dementia caregivers beyond the supports and services currently in place for dementia caregivers.

With the above discussion in mind, I propose to use a mixed-method design of both quantitative and qualitative approaches to explore the needs of caregivers of atypical dementias. Specifically, individual phone interviews with both typical dementia and atypical dementia caregivers will be conducted with the major focus on examining whether the current services for dementia caregivers are adequate for atypical dementia caregivers and, if they are not, on formulating service solutions based upon the information obtained from these caregivers.

The main objective of this study is to gain a greater understanding of the needs of atypical dementia caregivers and to assess the degree to which current dementia services meet those needs. Ultimately, a better understanding of the needs of these caregivers will help us to identify ways in which they can be better supported, thereby improving their ability to provide effective care and enhancing their quality of life.

As a final note, given that atypical forms of dementia are, by definition, fairly rare, focusing research on this area may not seem that pressing at present. However, as rates of dementia increase over the ensuing decades, those with atypical dementias stand to have a substantial impact upon the health care system. With this in mind, it is imperative that specific caregiving issues related to atypical dementias be dealt with while the number of individuals with this disease is still manageable.

In This Section

  • Research grant recipient Jennifer Marie Barker
  • Research grant recipient Megan Caines