Depressed or just frail? That’s the question
Richard C. Oude Voshaar
University of Groningen & University Medical Center Groningen, NL-Groningen
Background
Physical frailty is a (sub)clinical state characterized by diminished strength,
endurance, and reduced physiological function. In geriatric medicine, physical
frailty is considered an important medical syndrome that indicates an individual’s
vulnerability for developing dependency and/or mortality when exposed to
a stressor independent of multimorbidity and disability. Many studies on
frailty, however, exclude depressed older patients, as late-life depression
and frailty share most of their determinants and consequences.
The objective of this presentation is 1) to show that physical frailty can
be reliably and validly assessed among depressed older patients, and 2) to
show the predictive value of physical frailty in late-life depression with
respect to treatment outcome of depression (remission) and mortality.
Methods
Results will be based on several studies on frailty embedded within the Netherlands
Study on Depression in Older persons (NESDO). NESDO is a cohort study including
378 patients with a DSM-IV defined depressive disorder and a non-depressed
comparison group (n=132). Psychiatric diagnoses are based on a structured
diagnostic interview (CIDI). All participants were extensively assessed at
baseline, two- and six-year follow-up including the CIDI, self-report questionnaires,
physical examination including blood withdrawal, and cognitive testing. In
addition, symptom severity was monitored every 6 months by means of postal
questionnaires. Physical frailty was defined according to the Fried Frailty
Phenotype, based on unintended weight loss, gait speed, muscle strength,
exhaustion and low physical activity. Statistical analyses (ANOVA, linear
mixed models, logistic, linear en cox-regression) were fully adjusted for
potential confounders, including demographics, lifestyle, somatic morbidity
and cognitive functioning.
Results
The prevalence of physical frailty was 27.8% among depressed older patients
compared to 9.8% among non-depressed older persons (Collard et al, 2014).
Interestingly, within the NESDO study, we found no associations depressive
disorder and measures of low-graded inflammatory markers (hs-CRP, IL-6, NGAL)
and leucocyte telomere length, and only cross-sectionally with low vitamin
D levels (Van den Berg et al, 2018). However, among depressed patients (n=378),
physical frailty was significantly associated with low-graded inflammation
(Arts et al, J Am Geriatr Soc 2015), vitamin D deficiency (Van den Berg et
al, Ageing Ment Health 2018) and leucocyte telomere length (Arts et al, Exp
Gerontology, 2018).
As recently demonstrated in population-based studies as well as patient groups
suffering from specific somatic disorders, physical frailty also predicted
increased mortality rates over a six-year follow-up (HR=2.43 [95% CI: 1.33 – 4.43],
p=.004, adjusted for confounders). Interestingly, this effect was partly explained
by increased inflammatory markers, shortened leucocyte telomere length and
lower vitamin D levels. With respect to the course of depression, we found
that physical frailty predicted non-remission of late-life depressive disorder
(Collard et al, 2017).
Conclusion
Physical frailty is a valid construct that can be reliably measured among depressed
older patients, since 1) the prevalence of frailty in late-life depression
is significantly higher compared to non-depressed patients, 2) the prevalence
rate is comparable to those found among somatically ill older persons, and
3) frailty predicts increased mortality rates, which 4) can be explained
by aging-related biomarkers. Moreover, as frail depressed patients remain
significantly more depressed over a two-year follow-up compared to non-frail
depressed patients, we argue that a subgroup of depressed should not be considered
treatment resistant depression (and thus need more rigorous treatment for
depression), but simply classified as physically frail (and thus need integrated
treatment, including prevention of polypharmacy (especially TCAs), increasing
physical activity, and protein enriched diets.
References (all from my group, that will be shortly presented during the presentation):
1. Collard RM, Boter H, Schoevers RA, Oude Voshaar RC. Prevalence of frailty
in community-dwelling older persons: A systematic review. J Am Geriatr Soc
2012;60:1487-1492.
2. Collard RM, Comijs HC, Naarding P, Oude Voshaar RC. Physical frailty: Vulnerability
of patients suffering from late-life depression. Ageing Ment Health 2014;18:570-578.
3. Benraad CE, Kamerman-Celie F, van Munster BC,Oude Voshaar RC, Spijker J,
Olde Rikkert MG. Geriatric characteristics in randomized controlled trials
on antidepressant drugs for older adults: a systematic review. Int J Geriatr
Psychiatry 2016;31:990-1003.
4. Arts MH, Collard RM, Comijs HC, Naudé PJ, Risselada R, Naarding P,
Oude Voshaar RC. Relationship between physical frailty and low-grade inflammation
in late-life depression. J Am Geriatr Soc 2015;63:1652-1657.
5. Van den Berg KS, Arts MLS, van den Brink RHS, Comijs HC, Collard R, Marijnissen
RM, Oude Voshaar RC. Vitamin D deficiency and course of frailty in a depressed
older population. Aging Ment Health 2018, in press.
6. Van den Berg KS, Arts MLS, van den Brink RHS, Comijs HC, Collard R, Marijnissen
RM, Oude Voshaar RC. Vitamin D deficiency and course of frailty in a depressed
older population. Aging Ment Health, in press.
7. Arts MHL, Collard RM, Comijs HC, de Jonge L, Penninx BWJH, Naarding P, Kok
RM, Oude Voshaar RC. Leucocyte telomere length is no molecular marker of physical
frailty in late-life depression. Exp Gerontol 2018, in press
8. Arts MHL, Van den Berg KS, Marijnissen RM, Naarding P, Oude Voshaar RC.
The association between frailty and 6-year mortality rate in late-life depression
is mediated by low-graded inflammation, shortened leucocyte telomere length
and vitamin D deificiency. Manuscript in preparation.
9. Collard RM, Comijs HC, Naarding P, Penninx BW, Milaneschi Y, Ferrucci L,
Oude Voshaar RC. Frailty as a Predictor of the Incidence and Course of Depressed
Mood. J Am Med Dir Assoc 2015;16:509-514.
10. Collard RM, Arts MH, Schene AH, Naarding P, Oude Voshaar RC, Comijs HC.
The impact of frailty on depressive disorder in later life: Findings from the
Netherlands Study of Depression in Older Persons. European Psychiatry 2017;43:66-72.
11. Arts MH, Collard RM, Comijs HC, Zuidersma M, de Rooij SE, Naarding P, Oude
Voshaar RC. Physical frailty and cognitive functioning in depressed older adults:
Findings from the NESDO study. J Am Med Dir Assoc 2016;17:36-43.
12. Collard R, Arts M, Comijs HC, Naarding P, Verhaak P, de Waal MWM, Oude
Voshaar RC. The role of frailty in the association between depression and somatic
comorbidity: Results from baseline data of an ongoing prospective cohort study.
Int J Nurs Studies 2015;52:188-196.