Skip to main content Accessibility help
×
Home

[18F]FDDNP PET binding predicts change in executive function in a pilot clinical trial of geriatric depression

  • Beatrix Krause-Sorio (a1), Prabha Siddarth (a1), Kelsey T. Laird (a1), Linda Ercoli (a1), Katherine Narr (a2), Jorge R. Barrio (a3), Gary Small (a1) and Helen Lavretsky (a1)...

Abstract

Objectives:

Geriatric depression often presents with memory and cognitive complaints that are associated with increased risk for Alzheimer’s disease (AD). In a parent clinical trial of escitalopram combined with memantine or placebo for geriatric depression and subjective memory complaints, we found that memantine improved executive function and delayed recall performance at 12 months (NCT01902004). In this report, we used positron emission tomography (PET) to assess the relationship between in-vivo amyloid and tau brain biomarkers and clinical and cognitive treatment response.

Design:

In a randomized double-blind placebo-controlled trial, we measured 2-(1-{6-[(2-[F18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile ([18F]FDDNP) binding at baseline and assessed mood and cognitive performance at baseline, posttreatment (6 months), and naturalistic follow-up (12 months).

Participants:

Twenty-two older adults with major depressive disorder and subjective memory complaints completed PET scans and were included in this report.

Results:

Across both treatment groups, higher frontal lobe [18F]FDDNP binding at baseline was associated with improvement in executive function at 6 months (corrected p = .045). This effect was no longer significant at 12 months (corrected p = .12). There was no association of regional [18F]FDDNP binding with change in mood symptoms (corrected p = .2).

Conclusions:

[18F]FDDNP binding may predict cognitive response to antidepressant treatment. Larger trials are required to further test the value of [18F]FDDNP binding as a biomarker for cognitive improvement with antidepressant treatment in geriatric depression.

Copyright

Corresponding author

Correspondence should be addressed to: Helen Lavretsky, Psychiatry-in-Residence, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, 760 Westwood Plaza, Los Angeles, CA 90095, USA. Phone: +310 794 4619; Fax: +310 206 4399. Email: hlavretsky@mednet.ucla.edu.

Footnotes

Hide All

Protocol:https://clinicaltrials.gov/ct2/show/NCT01902004

Footnotes

References

Hide All
American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Washington, DC: American Psychiatric Association.
Bejanin, A.et al. (2017). Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease. Brain: A Journal of Neurology, 140, 32863300. doi: 10.1093/brain/awx243.
Benton, A., Hamsher, K., Varney, R. N. and Spreen, O. (1983). Contribution to Neuropsychological Assessment: A Clinical Manual. New York: Oxford University Press.
Carpenter, C. R.et al. (2014). Predicting geriatric falls following an episode of emergency department care: a systematic review. Academic Emergency Medicine, 21, 10691082. doi: 10.1111/acem.12488.
Cho, H.et al. (2016a). In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum. Annals of Neurology, 80, 247258. doi: 10.1002/ana.24711.
Cho, H.et al. (2016b). Tau PET in Alzheimer disease and mild cognitive impairment. Neurology, 87, 375. doi: 10.1212/WNL.0000000000002892.
Cole, G. B.et al. (2018). The value of in vitro binding as predictor of in vivo results: a case for [(18)F]FDDNP PET. Molecular Imaging and Biology, 21, 2534. doi: 10.1007/s11307-018-1210-2.
Conover, W. J. (2012). The rank transformation—an easy and intuitive way to connect many nonparametric methods to their parametric counterparts. WIREs Computational Statistics, 4, 432438. doi: 10.1002/wics.1216.
Conover, W. J. and Iman, R. L. (1981). Rank transformations as a bridge between parametric and nonparametric statistics. The American Statistician, 35(3), 24129. doi: 10.2307/2683975.
Delis, D. C. (2000). California Verbal Learning Test: Adult Version Manual. San Antonio, TX: Psychological Corporation.
Diniz, B. S., Butters, M. A., Albert, S. M., Dew, M. A. and Reynolds, C. F., 3rd (2013). Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. British Journal of Psychiatry, 202, 329–35. doi: 10.1192/bjp.bp.112.118307.
Eyre, H. A.et al. (2017). Neural correlates of apathy in late-life depression: a pilot [(18) F]FDDNP positron emission tomography study. Psychogeriatrics: The Official Journal of The Japanese Psychogeriatric Society, 17, 186193. doi: 10.1111/psyg.12213.
Folstein, M. F., Folstein, S. E. and Mchugh, P. R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–98. doi: 10.1016/0022-3956(75)90026-6.
Golden, C. J., Marsella, A. J. and Golden, E. E. (1975). Cognitive relationships of resistance to interference. Journal of Consulting and Clinical Psychology, 43, 432432. doi: 10.1037/h0076772.
Guy, W. (2000). Clinical Global Impressions (CGI) scale, modified. In: Rush, A. J. (Ed.), Task Force for the Handbook of Psychiatric Measures. Handbook of Psychiatric Measures, 1st ed.Washington, DC: American Psychiatric Association.
Hamilton, M. (1967). Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278296. doi: 10.1111/j.2044-8260.1967.tb00530.x.
Hostetler, E. D.et al. (2016). Preclinical characterization of 18F-MK-6240, a promising PET tracer for in vivo quantification of human neurofibrillary tangles. Journal of Nuclear Medicine, 57, 15991606. doi: 10.2967/jnumed.115.171678.
Hughes, C. P., Berg, L., Danziger, W. L., Coben, L. A. and Martin, R. L. (1982). A new clinical scale for the staging of dementia. British Journal of Psychiatry, 140, 566572. doi: 10.1192/bjp.140.6.566.
Ismail, Z., Fischer, C. and Mccall, W. V. (2013). What characterizes late-life depression? Psychiatric Clinics of North America, 36, 483496. doi: 10.1016/j.psc.2013.08.010.
Jack, C. R.et al. (2013). Update on hypothetical model of Alzheimer’s disease biomarkers. Lancet Neurology, 12, 207216. doi: 10.1016/S1474-4422(12)70291-0.
Klunk, W. E.et al. (2004). Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Annals of Neurology, 55, 306319. doi: 10.1002/ana.20009.
Kumar, A.et al. (2011). Protein binding in patients with late-life depression. Archives of General Psychiatry, 68, 11431150. doi: 10.1001/archgenpsychiatry.2011.122.
Lavretsky, H.et al. (2019). A randomized double-blind placebo-controlled trial of combined escitalopram and memantine for older adults with major depression and subjective memory complaints. American Journal of Geriatric Psychiatry. pii: S1064–7481(19)30474-9. doi: 10.1016/j.jagp.2019.08.011.
Lavretsky, H.et al. (2009). Depression and anxiety symptoms are associated with cerebral FDDNP-PET binding in middle-aged and older nondemented adults. American Journal of Geriatric Psychiatry, 17, 493502. doi: 10.1097/JGP.0b013e3181953b82.
Lezac, M., Howieson, D. and Loring, D. (2004). Neuropsychological Assessment. New York: Oxford University Press.
Liu, J.et al. (2007). High-yield, automated radiosynthesis of 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) ready for animal or human administration. Molecular Imaging and Biology, 9, 616. doi: 10.1007/s11307-006-0061-4.
Merrill, D. A.et al. (2012). Self-reported memory impairment and brain PET of amyloid and tau in middle-aged and older adults without dementia. International Psychogeriatrics, 24, 10761084. doi: 10.1017/s1041610212000051.
Meyers, J. E. and Meyers, K. R. (1995). Rey Complex Figure Test under four different administration procedures. Clinical Neuropsychologist, 9, 6367. doi: 10.1080/13854049508402059.
Mitchell, A. J. and Subramaniam, H. (2005). Prognosis of depression in old age compared to middle age: a systematic review of comparative studies. American Journal of Psychiatry, 162, 15881601. doi: 10.1176/appi.ajp.162.9.1588.
Murugan, N. A., Nordberg, A. and Ågren, H. (2018). Different positron emission tomography tau tracers bind to multiple binding sites on the tau fibril: insight from computational modeling. ACS Chemical Neuroscience, 9, 17571767. doi: 10.1021/acschemneuro.8b00093.
Palmqvist, S.et al. (2017). Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nature Communications, 8, 1214. doi: 10.1038/s41467-017-01150-x.
Reitan, R. M. and Wolfson, D. (1988). The Halstead-Reitan Neuropsychological Test Battery and REHABIT: a model for integrating evaluation and remediation of cognitive impairment. Cognitive Rehabilitation, 6, 1017. doi: 10.1007/978-1-4757-9820-3_4.
Rosen, C., Hansson, O., Blennow, K. and Zetterberg, H. (2013). Fluid biomarkers in Alzheimer’s disease—current concepts. Molecular Neurodegener, 8, 20. doi: 10.1186/1750-1326-8-20.
Shin, J., Lee, S. Y., Kim, S. H., Kim, Y. B. and Cho, S. J. (2008). Multitracer PET imaging of amyloid plaques and neurofibrillary tangles in Alzheimer’s disease. Neuroimage, 43, 236244. doi: 10.1016/j.neuroimage.2008.07.022.
Singh-Manoux, A.et al. (2017). Trajectories of depressive symptoms before diagnosis of dementia: a 28-year follow-up study. JAMA Psychiatry, 74, 712718. doi: 10.1001/jamapsychiatry.2017.0660.
Small, G. W.et al. (2012). Prediction of cognitive decline by positron emission tomography of brain amyloid and tau. Archives of Neurology, 69, 215222. doi: 10.1001/archneurol.2011.559.
Small, G. W.et al. (2006). PET of brain amyloid and tau in mild cognitive impairment. New England Journal of Medicine, 355, 26522663. doi: 10.1056/NEJMoa054625.
Sperling, R. A.et al. (2011). Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement, 7, 280292. doi: 10.1016/j.jalz.2011.03.003.
Tian, Y.et al. (2016). Venlafaxine treatment reduces the deficit of executive control of attention in patients with major depressive disorder. Scientific Reports, 6, 28028. doi: 10.1038/srep28028.
Tunvirachaisakul, C.et al. (2017). Predictors of treatment outcome in depression in later life: a systematic review and meta-analysis. Journal of Affective Disorders, 227, 164182. doi: 10.1016/j.jad.2017.10.008.
Vega, J. N.et al. (2016). Altered brain connectivity in early postmenopausal women with subjective cognitive impairment. Frontiers in Neuroscience, 10, 433. doi: 10.3389/fnins.2016.00433.
Villemagne, V. L.et al. (2013). Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurology, 12, 357367. doi: 10.1016/s1474-4422(13)70044-9.
Wagner, S.et al. (2018). Plasma brain-derived neurotrophic factor (pBDNF) and executive dysfunctions in patients with major depressive disorder. World Journal of Biological Psychiatry, 20, 519530. doi: 10.1080/15622975.2018.1425478.
Wechsler, D. (1997). The Wechsler Adult Intelligence Scale, III Manual. San Antonio, TX: Psychological Corporation.
Wilkins, C. H., Mathews, J. and Sheline, Y. I. (2009). Late life depression with cognitive impairment: evaluation and treatment. Clinical Interventions in Aging, 4, 5157.
Winblad, B.et al. (2004). Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. Journal of Internal Medicine, 256, 240246. doi: 10.1111/j.1365-2796.2004.01380.x.

Keywords

Type Description Title
WORD
Supplementary materials

Krause-Sorio et al. supplementary material
Krause-Sorio et al. supplementary material

 Word (14 KB)
14 KB

[18F]FDDNP PET binding predicts change in executive function in a pilot clinical trial of geriatric depression

  • Beatrix Krause-Sorio (a1), Prabha Siddarth (a1), Kelsey T. Laird (a1), Linda Ercoli (a1), Katherine Narr (a2), Jorge R. Barrio (a3), Gary Small (a1) and Helen Lavretsky (a1)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed