Evidence for a Geroscience Approach to Late Life Depression: Bioenergetics and the Frail-Depressed

Abstract

Late Life depression (LLD) is highly prevalent, with its course marked by declines in physical, cognitive, and emotional functioning. 1 Alexopoulos GS. Mechanisms and treatment of late-life depression. Transl Psychiatry. 2019; 9: 188 Google Scholar , 2 Chapman DP Perry GS. Depression as a major component of public health for older adults. Prev Chronic Dis. 2008; 5: A22 Google Scholar , 3 Kennedy G. The dynamics of depression and disability. Am J Geriatr Psychiatry. 2001; 9: 99-101 Google Scholar , 4 Meeks TW Vahia IV Lavretsky H et al. A tune in "a minor" can "b major": a review of epidemiology, illness course, and public health implications of subthreshold depression in older adults. J Affect Disord. 2011; 129: 126-142 Google Scholar , 5 Rutherford BR Taylor WD Brown PJ et al. Biological aging and the future of geriatric psychiatry. J Gerontol A Biol Sci Med Sci. 2017; 72: 343-352 Google Scholar LLD places increased demand on family caregivers, results in greater service utilization, and complicates treatment adherence for comorbid medical conditions, with subsequent degradations in quality of life and increased mortality risk. 6 Charney DS Reynolds 3rd, CF Lewis L et al. Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life. Arch Gen Psychiatry. 2003; 60: 664-672 Google Scholar Adults with LLD are at greatest risk for suicide of all demographic groups, with half of late life suicides following a visit to a medical provider the month prior. 7 Luoma JB Martin CE Pearson JL. Contact with mental health and primary care providers before suicide: a review of the evidence. Am J Psychiatry. 2002; 159: 909-916 Google Scholar , 8 Raue PJ Ghesquiere AR Bruce ML. Suicide risk in primary care: identification and management in older adults. Curr Psychiatry Rep. 2014; 16: 466 Google Scholar , 9 Van Orden K Conwell Y. Suicides in late life. Curr Psychiatry Rep. 2011; 13: 234-241 Google Scholar The deleterious course of LLD and the associated personal, social, and economic costs are due in part to higher rates of treatment resistance to antidepressant medication strategies. Rates of treatment resistance are substantially more common in older than in younger adults. 10 Buchalter ELF Oughli HA Lenze EJ et al. Predicting remission in late-life major depression: a clinical algorithm based upon past treatment history. J Clin Psychiatry. 2019; 80 (18m12483.) Google Scholar , 11 Mulsant BH Blumberger DM Ismail Z et al. A systematic approach to pharmacotherapy for geriatric major depression. Clin Geriatr Med. 2014; 30: 517-534 Google Scholar , 12 Sneed JR Culang ME Keilp JG et al. Antidepressant medication and executive dysfunction: a deleterious interaction in late-life depression. Am J Geriatr Psychiatry. 2010; 18: 128-135 Google Scholar For these reasons, long-term outcomes of LLD are bleak. 13 Deng Y McQuoid DR Potter GG et al. Predictors of recurrence in remitted late-life depression. Depress Anxiety. 2018; 35: 658-667 Google Scholar With societal demographic shifts towards older age, the onus falls on researchers to identify underlying mechanisms that complicate the treatment and course of LLD and contribute to its pathophysiology, then designing and implementing intervention strategies targeting these mechanisms to alter this deleterious clinical course of LLD.