Conflict of Interest Disclosure Corinne E Fischer, MD

1. Delusions, behavioural symptoms, quality of life and caregiver effects in Alzheimer’s Corinne E. Fischer MD FRCPC, Assistant Professor, University of Toronto, Director of the St. Michael’s Hospital Memory Disorders Clinic, St. Michael’s Hospital, Toronto, Canada

2. Conflict of Interest DisclosureCorinne E Fischer, MD Has no real or apparent conflicts of interest to report.

3. Background Delusions are a relatively common behavioural symptom of Alzheimer’s disease (AD) with a prevalence of about 31% (Bassiony et al 2000; Fischer et al, 2009). Prior studies have proposed a link between delusions and reduced frontal lobe integrity and function. Poor frontal lobe function has been linked to impaired performance of activities of daily living (ADLs) and instrumental ADLs (IADLs) (Royall et al 2002). This study examines whether delusional symptoms in AD are linked to more severe impairments in real world functioning. We predict the severity of real world function impairment will be mediated by deficits in frontal lobe abilities such as attention and executive function.

4. Background cont’d • Many prior studies have proposed a link between delusions and frontal lobe function • Binetti et al (1995) compared CT scans of delusional and non-delusional AD patients and found delusional patients had significantly more white matter lesions • SPECT studies have consistently shown decreased perfusion to the frontal lobes in delusional AD patients (Kotrla et al 1995, Mega et al 2000) • PET study by Sultzer et al (2003) showed decrease glucose uptake in the right prefrontal cortex in delusional AD patients

6. Background cont’d • Neuropathological studies have demonstrated that delusional AD patients may have more senile plaques in the frontal lobes (Zubenko et al 1991) • Neuropsychological studies have shown more impairment in frontal-executive tasks (Lopez et al 1997, Paulsen et al 2000) • Data suggests that delusions in AD patients may be associated with a number of adverse outcomes, including worse behavioural symptoms premature admission to Long Term Care and increased caregiving (Gormely et al 1998, Harwood et al 1999) • Recent data suggests that delusional AD patients may have worse functional performance (review, Fischer et al 2009)

7. Objectives To determine whether or not delusions in AD are associated with impairment in real world functioning. To determine whether or not impairment in real world functioning in delusional AD persons is mediated by reduced frontal lobe function. To determine whether impairment in real world functioning in delusional AD persons is associated with worse behavioural symptoms, reduced quality of life or increased caregiving.

8. Methods Participants were recruited through outpatient clinics at St. Michael’s hospital and from several affiliated Long Term Care Homes. Participants and caregivers were administered neuropsychological tests (MMSE, NART, Trail Making Test, Boston Naming Test, Token Test, CVLT) and questionnaires to measure real world function (DADS), behaviour (BEHAVE-AD), quality of life (AD quality of life) and caregiver effects (caregiver burden scale). Means were compared between groups using a 1-tailed independent samples t-test.

9. Results 15 delusional and 20 non-delusional AD participants have been tested thus far (matched for age and years of education). Both delusional and non-delusional AD participants performed similarly on a number of neuropsychological tests (MMSE, NART, Trail Making Test, Boston Naming Test, Token Test, CVLT) suggesting that their overall cognitive status is similar. Delusional AD participants performed worse than non-delusional AD participants during the planning stage of a verbal fluency task (first fifteen seconds) suggesting worse executive function.

10. Delusional AD participants perform worse than non-delusional participants during the planning stage of word generation (which is the first 15 seconds of a verbal fluency task), suggesting more impairment in executive function

11. Delusional AD participants have more behavioral changes as reported by their caregiver on the BEHAVE-AD. No differences were detected in quality life, however.

12. Delusional AD participants have more impairment in instrumental activities of daily living than non-delusional AD participants

13. Caregivers of delusional AD participants scored significantly higher on the Caregiver Burden Scale compared to caregivers of non-delusional AD participants

14. Clinical Implications These findings support the existence of a strong link between delusions in AD, frontal lobe dysfunction and real-world functional impairment. Future fMRI studies should attempt to localize differences in frontal lobe activation between delusional and non-delusional AD persons. Delusional AD persons are also not able to perform the same instrumental activities of daily living than non delusional AD persons and have more global changes in behavior as reported by their caregivers. No differences in quality of life were detected, however. Furthermore, these changes in functional ability in delusional AD persons may also contribute to increased caregiving. Knowledge gained from this study may provide guidance around the management of delusional AD persons, leading to improved treatment outcomes for patients and their families.

15. Acknowledgements • Co-PI: Dr. Tom Schweizer • Co-investigator: Dr. Zahinoor Ismail, Dr. Nathan Herrmann • Neurology: Dr. Luis Fornazzari • Research Assistants: Jemcy Joy, Lauren Forrest, Areeba Adnan • Registered Nurse Clinicians: Lee Ringer, Marianne Saragosa • Alzheimer Society of Canada • Heather and Eric Donnelly Endowment, St. Michael’s Hospital Foundation, St. Michael’s Hospital