Frailty is a geriatric syndrome characterized by a decrease in physiological reserve and reduced resistance to stress, as a result of an accumulation of multiple deficits in physiological systems. Frailty increases the vulnerability to adverse events and is associated with the aging process. Several studies show an association between frailty syndrome and altered blood lymphocyte levels in different clinical conditions, which is therefore potentially useful for monitoring interventions to improve or delay frailty at least in a subgroup of frail individuals.
Reference Sorted by Year of Publication | Study Design | Sample Size (n) | Subjects (Sex and Age) | Participants | Frailty Assessment | Relationship between Total Lymphocyte Count and Frailty | ||||||||||||||
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Semba et al., 2005 [20] | Case-control study. |
Reference Sorted by Year of Publication | Study Design | Sample Size (n) | Subjects (Sex and Age) | Disease/Patients | Frailty Definition | Lymphocyte Subtypes Studied | Relationship between Lymphocyte and Subtypes Count and Frailty | |||||||||||||||||||||||||
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Semba et al., 2005 [20] | Case-control study | 122 | Community dwelling-women (cases) who died during 5 years of follow-up (mean age 76.9 ± 6,4 years) and women (controls) matched by age, frailty, and morbidities who survived during 7 years of follow-up (mean age 77.3 ± 6.8 years). | 61 women who died (cases) to 61 women who did not die (controls) during follow-up were matched | Community-dwelling adults. | Fried’s criteria. | There were no significant differences in counts or percentages of lymphocytes between frail, pre-frail, and non-frail women. | |||||||||||||||||||||||||
Women (cases) with a mean age of 76.9 (6.4) years and women (controls) 77.3 (±6.8) years. | Community-dwelling adults. | Fried’s criteria. | Counts or percentages of CD4+, CD8+, CD4+CD28-, CD4+CD28+, CD8+CD28-, CD8+CD28-, CD4+CD45RA+, CD4+CD45RO+, CD8+CD45RA+, CD8+CD45RO+ T cells and CD4/CD8 T cells ratio. | Frail women appeared to have significantly higher CD8+ and CD8+CD28− lymphocyte counts. Frail women also had significantly lower CD4+, lower CD4+CD28+, higher CD8+, higher CD8+CD28-, and lower CD8+CD28+ percentages | De Fanis et al., 2008 [23] | |||||||||||||||||||||||||||
De Fanis et al., 2008 [23]Case-control study. | 26 | 22 women and 4 men with a mean age of 83.8 ± 5.3 years (range 72–94). | Community-dwelling adults. | Fried’s criteria | No significant differences in total lymphocyte counts between frail and non-frail participants were observed. | |||||||||||||||||||||||||||
Case-control study | 26 frail and no frail participants were matched. | 84,6 % were women and 15.4% men with a mean age of 83.8 ± 5.3 years (range 72–94). | Community-dwelling adults. | Fried’s criteria | Counts of CD3+, CD4+, CD8+, CD45RO+,CD45RO-, CCR5+, CCR5+ CD4+, CCR5+CD8+, CCR5+CD45RO+ and CCR5+CD45RO-T cells. | Frail participants had higher CCR5+, CCR5+CD8+, and CCR5+CD45RO- T-cell counts than matched non-frail controls. | Leng et al., 2009 [10] | |||||||||||||||||||||||||
Collerton et al., 2012 [12]Observational cohort study. | Cross-sectional study | 1106 | 845 patients. | Women from the WHAS I cohorts with an age range of 65–102 years and women from the merged WHAS I and II cohorts with an age range of 70–79 years. | +85 year old. | Community-dwelling woman. | Community-dwelling or institutionalized older people. | Fried’s criteria. | No significant association between total counts of lymphocytes with frailty was identified. | |||||||||||||||||||||||
Rockwood frailty index and scale Fried. | Count and ratios of CD4/CD8 T cells, memory/naïve CD4 and CD8 T cells and memory/naïve B cells. | High levels lymphocytes memory/naïve CD8 T cell ratio were associated with a lower risk of frailty on the Fried scale and low levels of memory/naïve B cells were associated with a higher risk of frailty on the Rockwood frailty index. | Collerton et al., 2012 [12] | |||||||||||||||||||||||||||||
Marcos-Pérez et al., 2019 [38]Cross-sectional study. | 845 | Different cohorts with a percentage of women in each cohort ranging from 60 to 75%. All participants were over 85 years old. | Community-dwelling or institutionalized older people. | Cross-sectional study | Rockwood frailty index and Fried’s criteria. | 259 patients. | 85 male and 174 female with an age range of 65–102 years. | The total lymphocyte count was inversely related to both measures of frailty, Fried scale and the Rockwood frailty index. | ||||||||||||||||||||||||
Patients were contacted through associations of older or retired people, day-care centers, and nursing homes. | Fried’s criteria. | Percentages of CD3+, CD4+ and CD8+ T cells, CD19+ B cells, CD16+56+ NK cells and CD4/CD8 T cells ratio. | A significant increase in the CD4+/CD8+ ratio and a significant decrease in the % CD19+ cells were observed in the frail group. | Fernández-Garrido et al., 2014 [16] | Cross-sectional study. | 42 | Women with an average age of 84.2 (±6.5) years (range, 70–99 years). | |||||||||||||||||||||||||
Samson et al., 2020 [39] | Observational cohort study. | Non-demented institutionalized older population. | 289 patients. | 145 men and 144 women between 60–87 years of age. | Fried’s criteria. | There was a significant and inverse relationship between the number of fulfilled frailty criteria and the lymphocyte count. | ||||||||||||||||||||||||||
Elderly people. | Frailty index with incorporates 36 possible “health deficits” | The numbers of CD16 and CD56 NK cells, CD56+ T cells and CCR7 + CD4 +/CD8 T cells, which were classified as naïve (CCR7+CD45RA+) or central memory (CCR7 + CD45RA-) T cells. CCR7-CD4 +/CD8 + T cells were divided into effector memory T cells (Tem, CCR7-CD45RA-) and effector memory T cells that re-express CD45RA T cells (TemRA, CCR7-CD45RA +). | More frail women, but not men, showed fewer CD56 + T cells and fewer CD4 + TemRA cells. | Nishijima et al., 2017 [21] | Cross-sectional study. | 133 | 54 women and 79 men with a median age of 74 years (range 65–92). | Cancer patients. | 36-item CFI. | Although the lymphocyte count in isolation was not related to frailty, the NLR was positively correlated with the frailty. Patients with a higher NLR also had increased odds of being frail/pre-frail. | ||||||||||||||||||||||
Hou et al., 2018 [36] | Cross-sectional study. | 345 | 154 women and 191 men with a median age of 71.0 years (IQR 65.0–77.0 years). | Elderly patients with coronary heart disease, (ACS (83.6%) and single-vessel disease (66.4%)). | Fried’s criteria. | A significant positive correlation was observed between NLR and the frailty score, and increased odds of being frail. | ||||||||||||||||||||||||||
Fernández-Garrido et al., 2018 [32] | Two-year follow-up study. | 94 | Women with an average age of 82 (±7) years. | Non-demented institutionalized older women. | Fried’s criteria. | There was a significant inverse correlation between the frailty scores and lymphocyte counts at baseline, but not at follow-up. | ||||||||||||||||||||||||||
Bernabeu-Wittel et al., 2019 [27] | Multicenter cohort study. | 444 | 200 women and 244 men with an average age of 77.3 (±8.4) years. | Community-dwelling (93.7%) and institutionalized (6.3%) older patients (outpatients in the Internal Medicine and Geriatric areas). | Fried’s criteria. | The combined presence of frailty and sarcopenia was associated with a lower lymphocyte count. | ||||||||||||||||||||||||||
Wilson et al., 2019 [19] | Observational cohort study. | 377 | 185 women and 192 men with an average of 73.7 years (range, 50–98 years). | Patients hip fracture. | Modified 11-item frailty index score. | Total lymphocyte count weakly inversely correlated with frailty. | ||||||||||||||||||||||||||
Navarro Martínez et al., 2019 [37] | Cross-sectional clinical trial. | 46 | Men with an average age of 72.2 (±9.4) years (range, 51–92 years). | Patients with prostate cancer undergoing antiandrogen therapy. | Fried’s criteria. | The lymphocyte counts were significantly lower in both frail and prefrail individuals than in robust individuals. | ||||||||||||||||||||||||||
Marcos-Pérez et al., 2019 [38] | Cross-sectional study. | 259 | 174 women and 85 men with an age range of 65–102 years. | Patients were contacted through associations of older or retired people, day care centers, and nursing homes. | Fried’s criteria. | The relationship between frailty and lymphocyte count was not studied in isolation. | ||||||||||||||||||||||||||
Núñez et al., 2020 [18] | Observational study. | 488 | 200 women and 188 men with an average age of 78 (±7) years. | Patients surviving an episode of an ACS. | Fried’s criteria. | The low percentage of lymphocytes was associated with frailty and a higher risk of being frail. | ||||||||||||||||||||||||||
Buigues et al., 2020 [28] | One-year follow-up study. | 39 | Men with an average age of 71.9 (± 9.8) years. | Patients with prostate cancer undergoing antiandrogen therapy. | Fried’s criteria | At baseline lower lymphocytes count were significantly correlated with the frailty syndrome severity and predicted its progression at one year of follow-up. | ||||||||||||||||||||||||||
Samson et al., 2020 [39] | Observational cohort study. | 289 | 144 women and 145 men between 60–87 years of age. | Elderly people. | Frailty index containing 36 possible “health deficits”. | The relationship between frailty and the total lymphocyte count was not studied (they studied separately subpopulations of T cells, B cells, NK cells counts). | ||||||||||||||||||||||||||
Bodolea et al., 2020 [26] | Observational cohort study. | 179 | 101 women and 78 men with an average age of 65.07 (±12.9) years (range, 23–90 years). | Patients with cardiovascular disease | Fried’s criteria. | Lower lymphocyte count and NLR were significantly correlated with the frailty syndrome and its severity. | ||||||||||||||||||||||||||
Bilgin et al., 2021 [30] | Observational cohort study. | 108 | 57 women and 51 men. Median ages of the frail and non-frail groups were 65 (50–78) years and 62 (50–79) years, respectively. | Patients with type 2 diabetes mellitus. | Edmonton Frail Scale. | Elevated MPVLR were significantly correlated with the frailty syndrome and its severity. | ||||||||||||||||||||||||||
Gilmore et al., 2021 [29] | Longitudinal cohort study. | 581 | Women. Age range, 22–81 years. | Women with stage I-IIIC breast cancer. | Fried’s criteria modified | Low lymphocyte counts and the NLR were associated with post-chemotherapy frailty, as well as changes in frailty from pre-chemotherapy to post-chemotherapy. |
ACS: Acute coronary syndromes; CFI: Carolina Frailty Index; IQR: Interquartile range; MPVLR: Mean platelet volume/lymphocyte ratio; NLR: Neutrophil to lymphocyte ratio; WHAS: Women’s Health and Aging Study.