Post-stroke Depression in the Very Elderly Rate and Predictive Factors


 Background: Post-stroke depression (PSD) affects 25–32% stroke survivors. PSD is quality-of-life altering and negatively impacts stroke recovery and mortality. Stroke incidence increases exponentially with age, especially >65 years, but no studies have yet specifically evaluated PSD in older stroke survivors. Because the very elderly are more prone to developing depression, we hypothesized a relatively high PSD rate for them. Methods: Consecutive stroke patients ≥75 years old, admitted to an acute stroke unit, were screened for depression with the Montgomery-Åsberg Depression Rating Scale or Aphasic Depression Rating Scale for aphasic patients, ≥15 days to 1-year post-stroke. Potential factors predictive of PSD were assessed. Results: Among 441 consecutive stroke patients, only 78 (17%) patients were evaluated because of high mortality and exclusion criteria. Among them, 44.8% (35/78) developed PSD: 22/78 (28.2%) mild and 11/78 (14.1%) moderate. Multivariate analysis retained only ≥1 mRS-point gain as being independently associated with PSD (OR, 6.2 (95% CI, 1.3–29.2), P=0.020). Conclusion: Our results confirmed the expected high PSD rate in patients ≥75 years, and suggest that PSD should be sought systematically or prophylactic antidepressants prescribed >15 days post-stroke for patients with ≥1 mRS-point gain.


Background
Strokes represent the second leading cause of death worldwide, with 6.5 million deaths annually. 1 Stroke incidence of increases with age, especially > 75 years. Post-stroke depression (PSD) is survivors' most common psychiatric complication, with rst symptoms usually appearing shortly after the acute event. 2 Long-term, PSD (affecting 29% (25-32%) 2 is associated with lower and slower neurological recovery, and higher mortality. 3 No study has focused speci cally on PSD in geriatric patients, those most at-risk for stroke. Moreover, the very elderly are more prone to developing depression. 4 Because many stroke victims are aged, we hypothesized more older survivors would have PSD, making it a major clinical issue.
This study was undertaken to evaluate PSD frequency in stroke survivors ≥ 75 years and to identify their PSD-associated factors.

Clinical Neurovascular Factors
National Institute of Health Stroke Scale (NIHSS) score for neurological severity at admission or after a recanalization procedure; Language Screening Test score (LAST) score for aphasia detection and assessment 5 ; Mini-Mental State Examination (MMSE) score to detect and evaluate cognitive impairment; modi ed Rankin Scale (mRS) score for functional independence, before and after stroke, with mRS score > 2 de ning dependence. We also categorized patients according to their transition from independence (mRS≤2) to dependence (mRS > 2), or a ≥ 1 mRS-point gain post-stroke.

Statistical Analysis
Comparisons used Student's t-test for quantitative variables and Pearson's χ 2 test for qualitative variables, with a bilateral 5% alpha risk and 10% beta risk. Univariate analyses used a logistic-regression model to identify associations between the different explanatory variables (qualitative and quantitative) and the dependent variable PSD. Only explanatory parameters achieving P < 0.25 in univariate analyses were included in the multivariate logistic analysis, whose signi cance threshold was set at P < 0.05. To avoid incorporating factors likely to bias multivariate analysis ndings because of multi-colinearity, parameters selected by the univariate analyses were tested for colinearity before being entered into the model.
Among the 69/78 patients functionally independent (modi ed Rankin scale score (mRS)≤2) pre-stroke, 23 became dependent (mRS > 2) post-stroke; 46 remained independent; 40 gained ≥ 1 mRS points, including 18 retaining in the same functional category post-stroke. Other characteristics are detailed in the Table 1 and in additional Table S1.  (11). Mean stroke-to-evaluation interval was 126 ± 86 days, with 34 (44%) assessed before 3 months, 44 (56%) thereafter, yielding respective PSD rates of 41% and 48% (P = 0.37). Ten patients took selective serotonin-reuptake inhibitors (SSRIs) for "depression" in the 6 months preceding stroke. Table 2 reports PSD-associated factors identi ed by univariate analyses. Because all factors concerning functional dependence post-stroke demonstrated colinearity, only "≥1 mRS-point gain" (univariate analysis PSD association P = 0.0001) was included in the multivariate analysis. That factor encompasses mRS change and independence-to-dependence transition, while providing more subtle notions (eg the loss of only minor functional independence) and maintaining the same independence/dependence category; it was also the only one retained by multivariate analysis as being independently and signi cantly PSD-associated. The close outcome-PSD relationship is clearly illustrated by patients' depression diagnoses: 17/23 (73.4%) who became dependent post-stroke, and 25/40 (62.5%) with ≥ 1 mRS-point gain. Discussion ≥ ≥ Our very elderly stroke population's overall PSD rate, assessed a mean of ∼4 months post-stroke, reached 44.8%, with no signi cant difference for those evaluated before or 3 months post-event. Our PSD patients' MADRS-assessed depression intensity was moderate/severe for 39%. Stroke-attributable ≥ 1 mRS-point gain was the only independent PSD predictor.
Study-population neurological parameters (relatively small parenchymal lesion volume, mean admission NIHSS = 2.25, mean mRS = 1.8 post-stroke) highlighted relatively low overall stroke severity, keeping in mind that patients with communication impairment or severe disability were excluded, which represents an important limitation.
However, our results re ect real-world stroke in the very elderly, as < 20% can be assessed for PSD after the acute phase. Nonetheless, considering post-stroke functional disability as the main PSD predictor, we think our results probably underestimate the real PSD rate. Indeed, PSD was common after minor strokes, but its cumulative rate was lower than for all-type-stroke survivors. 9 Despite diverse screening methods used to detect PSD, a meta-analysis showed a relatively constant ∼30% PSD rate, regardless of the time-to-assessment until 10 years. 2 Those patients' mean age was 65-71 years, ∼15 younger than our speci cally geriatric PSD population. The relatively high PSD rate in very old stroke survivors might be explained by the elderly's overall high vulnerability to depression, and their relatively low capacity for mental readjustment to their new acute stroke-generated state. 4 Also, their relatively short life expectancy and low probability of returning to their pre-stroke state can contribute to frequent loss of morale. Depression prevalences for the elderly in the general population are 4.4% (75-84 years) and 5% (≥ 85 years) ; 10 its risk is multiplied by ∼10 for aged stroke victims.
PSD impact on our patients' quality of life (QOL) is di cult to evaluate and represents another limitation. However, even a mild mood disorder has been shown to negatively affect stroke survivors' long-term QOL, 2,9 meaning clinical detection of even a mild morale dip could improve their QOL.
What do our results bring to clinical practice? The recent large, randomized FOCUS, AFFINITY and EFFECTS trials did not con rm the initially positive effect of uoxetine, an SSRI, on stroke recovery. [11][12][13] Although their results clearly demonstrated uoxetine e cacy against PSD, it was unfortunately offset by the doubled bone-fracture risk. 11-13 Therefore, post-stroke patients at-risk of PSD must be identi ed instead of systematically prescribed preventive antidepressants. Our observations suggest that a ≥ 1 mRS-point gain after the stroke's acute phase, regardless of the nal functional grade, can identify very elderly patients at high risk of developing PSD, for whom depression screening or even preventive antidepressant therapy could be justi ed.

Declarations
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