Background
Methods and measurements
Participants and data sources
Laboratory examinations
Measures of cognitive function
Measures of physical function
Relative handgrip strength (RHGS)
Covariates
Statistical analysis
Results
Variable | Total (2426) | Anemic (223) | Non-anemic (2777) | P-value | |
---|---|---|---|---|---|
Mean age (years) | 69.34 ± 6.39 | 69.16 ± 6.25 | 71.07 ± 7.43 | < 0.0001 | |
Female sex (%) | 1545 (51.50) | 108 (48.43) | 1340 (48.25) | 0.340 | |
Marital status, n (%) | Single | 25 (0.83) | – | 25 (0.90) | |
Married | 2248 (74.93) | 167 (74.89) | 2081 (74.94) | ||
Divorce | 26 (0.87) | 3 (1.35) | 23 (0.83) | ||
Widow | 701 (23.37) | 53 (23.77) | 648 (23.33) | ||
Mean hemoglobin concentration (g/dl) (SD) | Males | 15.06 ± 1.73 | 11.89 ± 0.95 | 15.41 ± 1.42 | 0.0001 |
Females | 13.96 ± 1.56 | 11.14 ± 0.87 | 14.22 ± 1.33 | 0.0001 | |
Mean BMI (kg/m2) | Males | 25.20 ± 4.01 | 25.20 ± 4.01 | 26.35 ± 4.00 | 0.003 |
Females | 28.70 ± 5.33 | 28.26 ± 6.10 | 28.74 ± 5.26 | 0.365 | |
Mean hand grip | 22.16 ± 9.23 | 19.88 ± 8.19 | 22.39 ± 9.29 | 0.0001 | |
Walking 4.57 m/s | 6.68 ± 5.75 | 7.15 ± 4.03 | 6.64 ± 5.89 | 0.203 | |
Positive for Hypertension | 1818 (75.16) | 178 (79.82) | 1640 (74.68) | 0.170 | |
Positive for Diabetes | 1228 (50.68) | 118 (52.91) | 1110 (50.45) | 0.713 | |
Positive Cognitive disorder, n (%) | 1194 (39.80) | 115 (51.57) | 1079 (38.85) | 0.0001 | |
Smoking | None | 735 (30.32) | 84 (37.67) | 651 (29.58) | 0.021 |
Past cigarette or hookah | 1185 (48.89) | 104 (46.64) | 1081 (49.11) | ||
current cigarette or hookah | 504 (20.79) | 35 (15.70) | 469 (21.31) | ||
Physical activity, n (%) | Not active | 155 (6.39) | 25 (11.21) | 130 (5.91) | 0.001 |
Sedentary | 1714 (70.71) | 164 (73.54) | 1550 (70.42) | ||
Low active | 397 (16.38) | 22 (9.87) | 375 (17.04) | ||
Active | 132 (5.45) | 8 (3.59) | 124 (5.63) | ||
Very active | 26 (1.07) | 4 (1.79) | 22 (1.00) |
Types of anemia | Anemia | ||
---|---|---|---|
Mild | Moderate to severe | Total | |
Microcyte anemia, n (%) | 19 (8.52) | 2 (0.90) | 21 (9.42) |
Normocyte anemia, n (%) | 189 (84.75) | 8 (3.59) | 197 (88.34) |
Macrocyte anemia, n (%) | 5 (2.24) | 0 (0.00) | 5 (2.24) |
Total, n (%) | 213 (95.52) | 10 (4.48) | 223 (100) |
Variable | Cognitive disorder | OR [95% CI] | P-value | |
---|---|---|---|---|
Positive | Negative | |||
RBC | 4.96 ± 0.66 | 5.06 ± 0.61 | 0.7 (0.65 to 0.89) | 0.0001 |
WBC | 7.35 ± 1.82 | 7.39 ± 2.49 | 0.99 (0.95 to 1.02) | 0.637 |
MCV | 85.78 ± 8.44 | 85.67 ± 8.14 | 1.00 (0.99 to 1.01) | 0.747 |
MCH | 29.73 ± 3.40 | 29. 88 ± 9.09 | 0.99 (0.9 to 1.00) | 0.56 |
RDW | 16.05 ± 54.73 | 14.38 ± 3.62 | 1.01 (0.98 to 1.04) | 0.445 |
RDWa | 75.68 ± 23.14 | 74.90 ± 20.32 | 1.00 (0.99 to 1.00) | 0.401 |
Hgb | 14.4 ± 1. 82 | 14.58 ± 1.65 | 0.94 (0. 89 to 0.98) | 0.009 |
HCT | 42.45 ± 5.06 | 43.19 ± 4.69 | 0.96 (0.95 to 0.98) | 0.0001 |
Outcome variable | Analytic model | All | Male | Female | |||
---|---|---|---|---|---|---|---|
β (95% CI) | P-value | β (95% CI) | P-value | β (95% CI) | P-value | ||
Hemoglobin a | |||||||
Category fluency test (semantic memory) | Crude | 0.20 (0.09 to 0.32) | 0.0001 | − 0.02 (− 0.19 to 0.14) | 0.781 | 0.03 (− 0.13 to 0.19) | 0.725 |
Model 1 | 0.14 (0.02 to 0.25) | 0.014 | −0.12 (− 0.29 to 0.04) | 0.148 | − 0.03 (− 0.19 to 0.12) | 0.681 | |
Model 2 | 0.09 (− 0.01 to 0.19) | 0.081 | 0.00 (− 0.15 to 0.16) | 0.922 | 0.07 (− 0.07 to 0.22) | 0.343 | |
Model 3 | 0.06 (−0.04 to 0.17) | 0.251 | −0.01 (− 0.17 to 0.14) | 0.838 | 0.05 (− 0.09 to 0.20) | 0.481 | |
Model 4 | 0.05 (−0.05 to 0.16) | 0.342 | −0.07 (− 0.23 to 0.08) | 0.365 | 0.01 (− 0.13 to 0.17) | 0. 809 | |
Late recall | Crude | 0.02 (0.00 to 0.04) | 0.028 | 0.02 (−0.00 to 0.06) | 0.140 | 0.02 (−0.00 to 0.06) | 0.112 |
Model 1 | 0.03 (0.01 to 0.05) | 0.003 | 0.03 (0.00 to 0.07) | 0.029 | 0.03 (0.00 to 0.07) | 0.038 | |
Model 2 | 0.03 (0.01 to 0.05) | 0.003 | 0.02(−0.01 to 0.05) | 0.198 | 0.02 (−0.00 to 0.06) | 0.154 | |
Model 3 | 0.03 (0.00 to 0.05) | 0.011 | 0.02 (−0.01 to 0.05) | 0.169 | 0.03 (−0.00 to 0.06) | 0.094 | |
Model 4 | 0.03 (0.00 to 0.05) | 0.010 | 0.02 (−0.01 to 0.05) | 0.185 | 0.03 (−0.00 to 0.06) | 0.080 | |
Mean hand grip | Crude | 1.69 (1.49 to 1.89) | 0.0001 | 0.80 (0.53 to 1.07) | 0.0001 | 0.36 (0.18 to 0.53) | 0.0001 |
Model 1 | 1.56 (1.36 to 1.75) | 0.0001 | 0.52 (0.28 to 0.76) | 0.0001 | 0.25 (0.09 to 0.42) | 0.002 | |
Model 2 | 1.50 (1.32to1.68) | 0.0001 | 0.84 (0.58 to 1.10) | 0.0001 | 0.38 (0.21 to 0. 56) | 0.0001 | |
Model 3 | 1.30 (1.11 to 1.48) | 0.0001 | 0.78 (0.52 to 1.04) | 0.0001 | 0.35 (0.17 to0.52) | 0.0001 | |
Model 4 | 1.30 (1.11 to 1. 48) | 0.0001 | 0.57 (90.31 to 0.83) | 0.0001 | 0.23 (0.06 to 0. 40) | 0.006 | |
Relative hand grip | Crude | 0.06 (0.05 to 0.07) | 0.0001 | 0.02 (0.01 to 0.03) | 0.0001 | 0.01 (0.00 to 0.01) | 0.001 |
Model 1 | 0.06 (0.05 to 0.06) | 0.0001 | 0.01 (0.00 to 0.02) | 0.019 | 0.00 (0.00 to 0.01) | 0.011 | |
Model 2 | 0.05 (0.04 to0.06) | 0.0001 | 0.02 (0.01 to 0.03) | 0.0001 | 0.01 (0.00 to 0.01) | 0.0001 | |
Model 3 | 0.04 (0.03 to 0.05) | 0.0001 | 0.01 (0.00 to 0.01) | 0.0001 | 0.01 (0.00 to 0.01) | 0.0001 | |
Model 4 | 0.04 (0.03 to 0.05) | 0.0001 | 0.01 (0.00 to 0.02) | 0.0001 | 0.00 (0.00 to 0.01) | 0.004 | |
Walking 4.57 m/s | Crude | −0.33 (− 0.46 to − 0.19) | 0.0001 | − 0.14 (− 0.25 to − 0.03) | 0.010 | − 0.17 (− 0.43 to 0.08) | 0.178 |
Model 1 | − 0.24 (− 0.36 to − 0.11) | 0.0001 | −0.06 (− 0.17 to 0.03) | 0.021 | − 0.05 (− 0.29 to 0.19) | 0.686 | |
Model 2 | −0.28 (− 0.41 to-0.14) | 0.0001 | − 0.15 (− 0.26 to − 0.04) | 0.007 | −0.20 (− 0.45 to 0.05) | 0.118 | |
Model 3 | −0.20(− 0.34 to − 0.07) | 0.002 | −0.14 (− 0.25 to − 0.03) | 0.013 | −0.14 (− 0.40 to 0.11) | 0.285 | |
Model 4 | −0.12 (− 0.22 to − 0.01) | 0.020 | −0.04(− 0.16 to 0.06) | 0.376 | 0.04 (− 0.13 to 0.22) | 0.589 |
Discussion
Author | Population baseline numbers descriptive Length of follow up | Type of study main outcome | Measurements Of cognition or hand grip | Measurements Of anemia | Adjusted for: | Relationship between anemia and cognitive | Statistics |
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Trevisa-n et al 2016 [53] | e Progetto Veneto Anziani project on, Italian population, 1227 participants older than 65 years old, without cognitive impairment mean follow up 4.4 (1.2SD) years | Cohort the onset of the cognitive impairment | the 30-item Mini-Mental State Examination (MMSE) | Based on WHO criteria Samples were Divided into the gender-specific Hb tertiles using the following cut-offs: 13.9 and 14.9 g/dL for men; and 12.8 and 13.7 g/dL for women. | Age, sex, education, smoking, alcohol, monthly income, living alone, physical activity, BMI, hearing loss, vision loss, hypertension, CVD, COPD, OAD, diabetes, cancer | Low hg concentration Increases the risk of cognitive impairment in the elderly, apparently with a stronger association in men than in women. | Participants with the lowest Hb concentrations had a significant 37% higher risk (95% confidence interval [CI]: 1.08–1.75; p = 0.01) of being diagnosed with cognitive impairment. Considering the gender separately, the risk of cognitive impairment only increased significantly, by 60%, for men in the lowest Hb tertile (95% CI: 1.06–2.41; p = 0.02), but not for women (hazard ratio = 1.32; 95% CI: 0.97–1.79; p = 0.08). |
Dlugaja et al 2015 [69] | 4033 participants from mandatory city registries in the Ruhr area in Germany, participant 45 to 75 years of age Five years follow up | Cohort Anemia and mild cognitive impairment | verbal memory measured by a word list consisting of eight words from the Nuremberg Geriatric Inventory Speed of processing/executive functioning was measured using the labyrinth test, a paper-pencil test from the NAI For mild cognitive impairment diagnosis: Participants were asked if their cognitive performance changed during the past two years, then statistical manual of mental disorders, | WHO criteria hemoglobin level < 13 g/dl in men and < 12 g/dl in women | Age, gender, BMI, education, diabetes, blood pressure hypertension, stroke, cancer, depression scale, smoking status, total cholesterol | Anemic participants showed lower performances in verbal memory and executive functions | Adjusted Odds ratios (OR) for mild cognitive impairment (MCI), amnestic- MCI, and non-amnestic-MCI in anemic versus non-anemic participants were 1.92 (95%-CI, 1.09–3.39), 1.96 (1.00–3.87), and 1.88 (0.91–3.87). |
Payne et al 2018 [13] | 4499 men and women aged 40 and over | cross-sectional data from a population-based study of rural South African men and women physical and cognitive performance | Grip strength was measured twice in both hands, using a Smedley digital dynamometer (12–0286). Walk speed was measured by asking participants to walk a 2.5 m course twice, with the time taken timed to the nearest 0.1 s. Cognitive performance was assessed with a cognitive battery adapted for language, cultural, and educational appropriateness from validated measures used in the U.S. Health and Retirement Study. | Hg concentration < 12 g/dL for women and < 13 g/dL for men | Age, sex, education, Median C reactive protein concentration, HIV, hypertension, diabetes mellitus, mean body mass index, and self-reported angina, chronic bronchitis, and stroke | There was no association between hemoglobin levels and walk speed or cognitive score Hemoglobin concentration Was independently associated With grip strength | Hemoglobin concentration Was independently associated With grip strength in women when covariates were included in the model (B = 0.391; 95% CI 0.177 to 0.605), but this association was not statistically significant in men (B = 0.266; 95% CI − 0.019 to 0.552 |
Qin et al 2019 [75] | 9324 adults aged 45 years or older from the China Health and Retirement Longitudinal Study | Cohort Association between Anemia and cognitive decline among Chinese middle-aged and elderly | Cognitive performance assessed by memory recall (episodic memory), mental status (TICS), and global cognitive function at baseline survey | WHO criteria hemoglobin level < 13 g/dl in men and < 12 g/dl in women | Age, gender, education, marital status, cigarette, smoking, body mass index, hypertension, diabetes, abdominal adiposity, chronic pain, dyslipidemia, CRP, HDL, and cholesterol | This study found a cross-sectional and longitudinal association between Anemia and accelerated decline in cognitive functions in Chinese middle-aged and elderly The hemoglobin concentration Was associated with global cognitive function global -cognitive function and episodic- memory was associated with anemia independent of covariates | After adjusting for socio-demographic and health-related covariates, the cross-sectional association between anemia and global cognitive function [β (95%CI) = − 0.49(− 0.69 ~ − 0.29)], episodic memory [β (95%CI) = − 0.14(− 0.23 ~ − 0.05)], and TICS [β (95%CI) = − 0.23(− 0.38 ~ − 0.08)] were significant and did not differ by gender. |
Joosten Et al 2016 [38] | 220 patients aged 70 years and older | Prospective study The relationship Between Anemia and handgrip and walking speed | Handgrip strength was assessed with a hydraulic hand dynamometer. Gait speed (in meters per second) was calculated after a 4.5 m walk ADL score | WHO criteria hemoglobin level < 13 g/dl in men and < 12 g/dl in women | Sex, age, BMI, ADL, CRP, GFR, MMSE mean, cancer, gastrointestinal diseases, −Neuropsychiatric diseases, Falls-fractures-osteoporosis | Handgrip, ADL score, and gait speed were not significantly different in anemic and non-anemic person | No significant correlation was found between the hemoglobin values and the hand-grip strength (Spearman’s rho 0.112, p = 0.1) and walking speed (Spearman’s rho 0.04, p = 0.69) |
Hong- bae et al 2019 [70]. | 16 observational studies, including eight case-control studies and eight cohort studies, were included in the final analysis In total, 16,765 cognitive impairment cases were surveyed in the meta-analysis. | Meta-Analyzed Studies reporting a relationship between Anemia and cognitive impairment from 1964 to July 10, 2019 | cognitive impairment in four articles was diagnosed using a cut-off score of 24 on the MMSE, and one article used the International Working Group (IWS) criteria | anemia was defined according to the WHO criteria of hemoglobin level < 13 g/dl in men and < 12 g/dl in women | gender, mean age, duration of follow-up in cohort studies, number of participants, methodological quality, and studies that adjusted for education, cardiovascular risks, smoking status, apolipoprotein E carrier status, alcohol consumption, and physical activity were used in Sub-group meta-analyses | According to this meta-analyzed, There is a relationship between Anemia and cognitive impairment | Anemia was significantly linked to cognitive impairment (OR or RR 1.51; 95% CI: 1.32–1.73) in a random-effects meta-analysis |
Valladã-o Júnior et al 2020 [72] | 13,624 participants (mean ages = 51.6 years±9) | Cross-sectional study base on ELSA-Brazil Cohort | scores for verbal learning, late recall, word recognition, a semantic verbal fluency test, and the Trail-Making Test, Part B (TMT-B) | WHO criteria hemoglobin level < 13 g/dl in men and < 12 g/dl in women | Education, race, monthly family income, excessive alcohol use, thyroid function, smoking status, hypertension, diabetes, dyslipidemia, body mass index, Antipsychotic, antiparkinsonian, or anticonvulsant drug use | Hemoglobin levels were not associated with global cognitive scores, | Global cognitive scores were similar between participants with and without anemia in adjusted models for the entire sample (b = − 0.004; 95% CI = –0.052, 0.044) or separately, for men (b = 0.047; 95% CI = –0.053, 0.146) and women (b = − 0.015; 95% CI = –0.070, 0.040) |
Jiang et al 2020 [71] | 4838 participants 65 years old and over | Cross-sectional | CognitivefunctionwasevaluatedusingtheMini-MentalStateExamination (MMSE) and neuropsychological test battery | WHO criteria hemoglobin level < 13 g/dl in men and < 12 g/dl in women | Demographic factors, lifestyle, and clinical condition | Anemia was associated with cognitive performance There was no relationship between Anemia and dementia | Anemia was associated with a multiple-adjusted odds ratio of 1.28 (95%CI:1.041.57) for MCI and 1.27 (95% CI: 0.87–1.85) for dementia, and a multiple-adjusted β coefficient of − 0.60 (95% CI: − 0.94 to − 0.27) for MMSE score |
Brenda et al 2004 [37] | 1156 participants aged 65 and older from CHIANTI Study (Italy) | Used data from the Italian National Research Council of Aging | ADL (6 item questioner) IADL (8 items) Walking speed: was defined as the best performance (time in seconds) of two 4-m walks. Standing balance: participants were asked to stand with the feet side by side, a semi tandem position, and a full-tandem position. Chair stand test: participants were asked to stand up from and sit down in a chair five times without using hands | World Health Organization (WHO) criteria hemoglobin level < 13 g/dl in men and < 12 g/dl in women | Age, sex, BMI, smoke, MMSE, diabetes mellitus, myocardial infection, Angina pectoris, Peripheral artery disease, Congestive heart failure, stroke, cancer, lung disease, Gastric ulcer, Hospitalization in the past year, Creatinine, mg/dL | Anemia is associated with disability, poorer physical performance, and lower muscle strength | anemic persons had more disabilities (1.71 vs 1.04, P = 0.002) and poorer performance (8.8 vs 9.6, P = 0.003), than persons without Anemia. Anemic persons also had significantly lower knee extensor strength (14.1vs 15.2 kg, P = 0.02) and lower handgrip strength (25.3vs27.1 kg, P = 0.04) than persons without Anemia |
Hirani et al 2016 [39] | 1705 Australian men aged 70 years old and over from the Concord Health and Ageing in Men Project Five years follow up | Cross-sectional study, The relationship between HG levels, and sarcopenia, low muscle strength, functional and activities of daily living (ADL), and instrumental ADL (IADL) disabilities in older | muscle strength was assessed by handgrip and participate divided in grip strength less than 26.0 kg versus grip strength 26.0 kg and more. Walking speed: was measure 4 mm speed. Participants with a walking speed of 0.8 m/s or less were classified as having low walking speed. ADL: was assessed by seven items from a modified version of the Katz ADL scale IADL: asks participants how much help they need to perform ten tasks considered necessary for independent living | World Health Organization (WHO) criteria Hb level less than 13 g/dL in men | age, income, body mass index, measures of health, estimated glomerular function, inflammatory markers, and medication use | Low hemoglobin concentration over time is associated with poor functional performance for every 1 g/dL increase in Hb, there was a significant reduction in risk of sarcopenia, slow walking speed, poor grip strength, inability to perform chair stands, and ADL and IADL disabilities | there was a association between Hb and grip strength β coefficient = 1.52, 95% CI = 1.27, 1.78 for unadjusted β coefficient = 1.05, 95% CI = 0.80, 1.30 for age-adjusted and β coefficient = 0.82; 95% CI = 0.55, 1.08, for multivariate-adjusted for walking speed: β coefficient = 0.03, 95% CI = 0.02, 0.03; for unadjusted β coefficient = 0.01, 95% CI = 0.01, 0.02; for age-adjusted and β coefficient = 0.01, 95% CI = 0.004, 0.02,, for multivariate-adjusted. |
Thein et al 2009 [45] | 328 participants 65 years and older | Cross-sectional study To determine the relationship between HG concentration and functional status, depression, disability, and physical strength, independent of chronic disease | IADL (consists of 13 questions) Handgrip strength: with a handheld dynamometer (in kg), using the mean value after performing the task three times | WHO criteria hemoglobin level < 13 g/dl in men and < 12 g/dl in women | Age, sex, diabetes, hypertension, chronic inflammation, or rheumatoid arthritis | There was a significant association of Anemia with declines in health-related quality of life, functional status, and physical strength | Anemia was associated with greater fatigue (P < 0.001), lower handgrip strength (P = 0.014), and increased number of disabilities (P = 0.005) |