This document summarizes a presentation on investigating cognitive function in geriatric mood disorders. The following key points were discussed: - Major depressive disorder and bipolar disorder are common in older adults and associated with cognitive dysfunction across multiple domains. - A study examined cognitive performance in older adults with MDD or BPAD compared to healthy elders, finding significant deficits in processing speed, executive function, verbal fluency, short-term recall. Illness severity correlated with poorer cognition. - Future directions include examining the effects of medical comorbidities on cognition longitudinally, and exploring imaging biomarkers to further characterize cognitive deficits in mood disorders. This may help develop targeted treatments to improve patient outcomes.

1. Investigation Cognitive Function
in Geriatric Mood Disorders
Jennifer R. Gatchel M.D., Ph.D.
Fellow, Geriatric Psychiatry
Harvard Medical School
Academy of Psychosomatic Medicine
61st Annual Meeting
Webb Fellowship Presentation
November 14, 2014

2. Disclosures for Jennifer Gatchel MD, PhD
• No disclosures or conflicts of interest related
to this presentation.

3. Outline
Background
Why is cognitive dysfunction in geriatric mood
disorders important to think about ?
Research study
How did we investigate this topic and what did we
find ?
Future directions
What are the implications and remaining questions ?

4. Geriatric MDD and BPAD are Common
– Major Depressive Disorder: 2.7 % of elders
(Community 1 yr prev.)
– Significant depressive symptoms: 8‐15 %
– Bipolar disorder: 0.1‐0.4 % of elders
• 6 % of geriatric outpatient visits
• 8‐10 % of geriatric inpatient admissions
• 3 % of nursing home residents
• 17 % of geriatric presentations to psychiatric ED
1. Hybels CF, Blazer DG. Epidemiology of late‐life mental disorders. Clin Geriatr Med. 2003
Nov;19(4):663‐96, Review. 2. Depp CA, et al. Bipolar Disord. 2004;6(5):343‐367
3. Depp CA, et al. Am J Geriatr Psychiatry. 2005;13(4):290‐298
4. Yassa R, et al. Psychiatr Clin North Am. 1988;11(1):117‐131.

5. Geriatric MDD and BPAD
• Chronic and disabling
–Medical and psychiatric co‐morbidities
–Cognitive dysfunction
Copeland et al., 2004, Costa et al., 2007 , Sajatovic et al., 2011, Diniz et al., 2011

6. Cognitive Dysfunction in Geriatric
MDD and BPAD
• Occurs across the age spectrum
• Associated with poorer functional outcomes
– Loss of productivity and decreased quality of life
• Affects multiple cognitive domains
– episodic memory, executive function, processing
speed
• Persists during euthymic periods
Gildengers et al., 2013; Diniz et al., 2011; Xu et al. J Affective Disorders 2012

7. Cognitive Dysfunction in Geriatric
MDD vs. BPAD
• Few comparative studies in younger, mixed‐aged
populations: differences may exist
– BPAD: information processing speed and episodic
memory
– MDD: verbal fluency, executive function
• No comparative studies in geriatric populations with mood
symptoms
Balanza‐Martinez et al., 2010

8. Additional questions
• Trait and state dependence ?
• Relation to clinical variables ?
• Longitudinal course ?
• Relationship to dementia ?
Balanza‐Martinez et al., 2010; Gildengers et al., 2004; Gunning‐Dixon et al., 2008

9. II. Research Study: Objectives
• Examine different domains of cognitive
function in geriatric MDD and BPAD
• Investigate effects of illness severity on
cognitive function
• Determine whether there are MDD‐ vs. BPAD‐
specific changes

10. Hypotheses
• Older adults with MDD and BPAD will have
deficits across multiple cognitive domains
relative to healthy elders.
• Severity of illness will predict poorer cognitive
performance.
• Patterns of cognitive deficits relative to
healthy elders will differ between older adults
with MDD and BPAD.

11. Methods…
• Secondary analysis of data collected in six
ongoing studies in the McLean Geriatric
Psychiatry Research Program
– Three treatment studies for geriatric
BPAD, two for MDD
–One longitudinal study for MDD and BPAD

12. Methods…
• Inclusion Criteria
– Diagnosis of Major Depressive Disorder or Bipolar
Disorder Type I
• Exclusion Criteria
– Current DSM IV TR diagnosis of dementia, depressive
disorder NOS, Bipolar Disorder Type II
– Mini Mental Status Exam <24
– Electroconvulsive therapy in the preceding 6 months
– Substance abuse or dependence in preceding 12
months

13. Neuropsychological battery
Cognitive variable measured Instrument used
Intellectual functioning Wechsler Abbreviated Scale of Intelligence (WASI)
Visual confrontation naming Boston Naming Test (BNT)
General cognitive function Mini Mental Status Exam (MMSE)
Verbal fluency—phonemic
fluency
FAS
Verbal fluency—semantic
fluency
Category Fluency‐‐Animals
Processing speed Trails A, Trails B, Stroop Color and Word Task
Working memory Trails B
Executive function FAS, Trails B, Stroop Color and Word Task, Wisconsin
Card Sorting Task
Short‐term recall CERAD word list

14. Demographics
Characteristic Control MDD BPAD Significance
Age, mean (S.E.) 65.6 (1.3) 71.4 (1.4) 65.2 (1.2) p= 0.001
Female, N (%) 17 (28.3) 25 (41.7) 18 (30.0) p< 0.05
Years of education,
mean (S.E.)
16.4 (0.4) 15.2 (0.5) 16.1 (0.4) N.S.
Age of first episode,
mean (S.E.)
N/A 38.4 (2.9) 24.2 (2.6) p< 0.001
N = 129 subjects, control: 44; MDD: 37; BPAD: 48

15. * p<0.05; **p<=0.01; *** p<0.001.
Trails A Trails B
Stroop Color

16. * p<0.05; **p<=0.01; *** p<0.001.
FAS Category (Animals)
Phonemic Fluency Semantic Fluency

17. 20
30
40
50
60
Control MDD BPAD
20
30
40
50
60
70
Control MDD BPAD
Wisconsin Card Sorting Test CERAD Word List Recall
Control MDD BPAD Control MDD BPAD
Wisconsin Card Sorting Test Wisconsin Card Sorting Test CERAD Word List Recall TestCERAD Word List Recall Test
***
***
***
***
***
*** p<0.001
Executive Function Short‐term recall

18. Hypotheses
• Older adults with MDD and BPAD will have
deficits across multiple cognitive domains
relative to healthy elders
• Severity of illness will predict poorer cognitive
performance
• Older adults with BPAD vs. MDD will be more
impaired relative to healthy elders in specific
cognitive domains

19. 0
10
20
30
40
50
control MDD BPAD
* p<0.05; **p<=0.01; *** p<0.001.
***
***
Chlorpromazine equivalents
Control MDD BPAD
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Control MDD BPADControl MDD BPAD
**
**
Diazepam equivalents
Baldessarini, RJ, Chemotherapy in Psychiatry
3rd ed, 2013

20. 0
10
20
30
40
50
control MDD BPAD
* p<0.05; **p<=0.01; *** p<0.001.
FAS Category (Animals)
***
***
CPZ‐eq
Control MDD BPAD
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Control MDD BPADControl MDD BPAD
**
**
Diaz‐eq

21. Conclusions
• Geriatric subjects with mood disorders: worse than
healthy elders in multiple cognitive domains
Processing speed
Executive function
Phonemic fluency
Semantic fluency
Short‐term recall

22. Conclusions
• Geriatric subjects with mood disorders: worse than
healthy elders in multiple cognitive domains
Processing speed
Executive function
Phonemic fluency
Semantic fluency
Short‐term recall
CPZ eq., Diaz eq.,
Depression
severity

23. Conclusions
• Geriatric subjects with mood disorders: worse than
healthy elders in multiple cognitive domains
Processing speed
Executive function
Phonemic fluency
Semantic fluency
Short‐term recall
CPZ eq., Diaz eq.,
Depression
severity
BPAD
MDD

24. Future directions
• Examination of effects of medical co‐morbidity on
cognitive performance
• Longitudinal measurement of cognitive performance
• Correlation with imaging biomarkers

25. Future directions
• Examination of effects of medical co‐morbidity on
cognitive performance
• Longitudinal measurement of cognitive performance
• Correlation with imaging biomarkers
• Further characterization of cognitive deficits and their
neurobiological basis may drive targeted treatments and
influence patient outcomes

26. Acknowledgments
McLean Hospital, Harvard Medical School:
• Brent P. Forester, M.D., Eve Lewandowski, Ph.D.
• David Harper, Ph.D., Nick Lange, Ph.D. Daniel Shassian
MGH/McLean Hospital Adult Psychiatry Residency Program:
• Ted Stern, M.D., Felicia Smith, M.D., Jerry Rosenbaum M.D., Maurizio
Fava, M.D., Scott Rauch, M.D., Shelly Greenfield, M.D., Justin Baker M.D.,
Ph.D., Dost Ongur, M.D., Ph.D., Joy Littlefield, Landy Georges, Patrick
Love
Academy of Psychosomatic Medicine: Webb Scholars Program :
• Scholarship Selection Committee; Ph.D.; Bob Boland, M.D., James Vrac
AAGP, GMHF Scholars Program:
• Kirsten Wilkins, M.D., Susan Schultz, M.D., Michelle Conroy, M.D., Olivia
Okereke, M.D., M.S., Paul Kirwin, M.D.

27. Questions?