Aging and SCD

Many experts define aging as a deterioration in physiological function that occurs over time [7, 8]. The World Health Organization defines healthy aging as the process of maintaining functional ability in older age, which includes the ability of individuals to be and do what they value [9]. Chronologic age does not accurately reflect health and functional status [10]. Individuals with similar chronologic age often have different functional capabilities and estimated life expectancy [11]. SCD and age-related changes can lead to impairments in function and disability. If functional impairments are identified early, healthcare providers can implement interventions to reduce functional decline and improve quality and quantity of life [12]. Failure to identify impairments early can lead to adverse outcomes, such as death, loss of independence, and a diminished ability to do activities and meet goals they value most in life. Therefore, establishing a patient’s baseline function will facilitate monitoring the trajectory of their health [13].

Current functional assessment tools in SCD

Current validated assessment tools used to evaluate health and function in adults with SCD are limited in what they are able to measure. The only physical performance test routinely used to assess patients with SCD is the six-minute walk test (6MWT), a measure of cardiorespiratory function and screening tool for pulmonary hypertension [14]. It has limited utility as it does not include assessments of strength or balance, which are factors that are especially vital to maintaining health, independence, and function in late life. Available condition-specific assessment tools, such as the Adult Sickle Cell Quality of Life Measurement System, ASCQ-Me, provide patient-reported data about important areas of health in adults with SCD, such as mental health, pain, sleep, and fatigue. However, these measures are limited in their ability to identify age-related conditions, such as frailty and dependence in activities of daily living and instrumental activities of daily living (ADL/IADL) [15].

Comprehensive Geriatric Assessment

Comprehensive Geriatric Assessment (CGA) is a process used to assess the capabilities and vulnerabilities in older adults and can be used to assess an individual’s physiologic or functional age. It measures multiple domains of health including functional status, physical performance, cognitive function, psychological state, nutritional status, social support, comorbidities, and polypharmacy [16]. The CGA gives a more accurate representation of a patient’s ability to adapt to the demands of daily life and can unearth unsuspected impairments in function often missed by routine clinical evaluations [10]. Geriatricians have used CGA for decades to guide therapeutic interventions. Oncologists most notably use CGA to assess risk of toxicity from chemotherapy in older adults and have also included younger adults with hematologic malignancies in these studies [10, 17, 18].

Data collection

Participants entered their demographics, complications from SCD, social history (e.g., education, annual household income, living arrangements, employment status), and healthcare utilization into a REDCap database. Investigators also recorded SCD complications, healthcare utilization, and steady-state laboratory values from the electronic medical record. All participants were assessed at steady-state, which we defined as greater than 6 weeks after their last hospitalization and greater than 2 weeks after their last emergency department (ED) or sickle cell day hospital visit. We confirmed participants were at steady-state by reviewing the medical record and asking the participant. We managed the data collection using REDCap electronic data capture tools [19, 20]. We included consensus measures from the Phenotypes and eXposures (PhenX) Toolkit when available [21]. Conflicts between self-report and investigator entered observations were handled by using medical history and healthcare utilization as documented in the electronic medical record.

Description of measures in the SCD-FA

The SCD-FA includes a combination of validated patient-reported questionnaires and performance-based measures administered by the study team (Table ​(Table1).1). This assessment focuses on key areas that are at the intersection of SCD and geriatrics collaboratively selected by SCD providers, geriatricians, and exercise specialists. We included measures from the oncology geriatric assessment developed by Hurria et al. [16, 17]. Measures were originally selected based on validity, brevity, reliability, and prognostic value [16, 17].

Table 1

Measures selected for the sickle cell disease functional assessment

Domains	Measures in each domain	Description
Functional Status	OARS Activities of Daily Living and Instrumental Activities of Daily Living	Measures the extent to which one is able to function independently. Scores range 0–28 with higher scores indicating more independence. (14 items)
	Physical Functioning Subscale of the SF-36	Component of the 36-Item Short Form Health Survey (SF-36). Measures extent to which health currently limits daily activities. Scores range 0–100, with higher scores indicating better physical functioning. (10 items)
	Karnofsky performance status—self and physician*	Global measure of physical ability. Scores 0–100 with higher scores indicating better performance (2 items). Score ≥80 indicates good performance status.
	Number of falls in last 6 months	Self-reported number of falls in the last 6 months. ≥1 fall indicates increased risk of subsequent falls. (1 item)
	Usual Gait Speed*	Comfortable walking pace on a 3-m (10 ft) course with an acceleration zone and deceleration zone. The fastest speed of 2 trials is used for the analysis. Scores compared to normative values based on age and gender.
	Timed Up and Go*	The time it takes to rise from a standard height chair (46cm), walk a distance of 10 ft (3 m), turn, walk back to the chair, and sit down again. Shortest time of 2 trials is used for the analysis. TUG assesses balance. TUG >10 s is associated with fractures in older adults and > 12 s indicates increased risk of falls.
	Dual-Task Performance*	Assesses the effects of simultaneously performing a cognitive and motor task: usual walking speed for 1 minute and a verbal fluency task using letters F, A, and S. Each task is performed once individually, then simultaneously twice using a different letter on each attempt. Scores are used to calculate whether cognitive-motor interference is present.
	Six-Minute Walk Test*	Distance walked in 6 minutes. 2-min and 6-min walking distances are recorded and heart rate recovery at 1 and 2 minutes. Scores compared to normative values based on age and gender.
	Seated Grip Strength*	Grip strength measured in triplicate alternating both hands using Jamar Technologies Hydraulic Hand Dynamometer while the participant remains seated in a standard height chair (46 cm). Scores compared to normative values based on age and gender.
	30-second Chair Stand*	Number of times one can rise to a standing position and sit back down in 30 seconds. Scores compared to normative values based on age and gender.
Comorbid Medical Conditions	OARS Physical Health questionnaire	Patient-reported comorbidity checklist and the degree to which the condition interferes with their daily activities. (27 items)
Psychological State	Mental Health Inventory-18 (MHI-18)	Includes anxiety, depression, behavioral control, and positive affect subscales. Total and subscale scores range 0–100, with higher scores indicating better mental health. (18 items)
Social Support/Social Activities	MOS Social Support Survey	Perceived availability of social support. Total score is on a 0–100 scale with lower scores indicating less support. (19 items)
	Social Functioning Subscale of the SF-36	Measures amount of time physical health or emotional health interfered with social activities over the last 4 weeks. Subscale scores range from 0-100 with higher scores indicating better social functioning. (1 item)
	MOS Social Activity Limitations Measure	Measures change in social activities and limitations in social activities compared to peers over the last 6 months. Mean of 2 items transformed to scores range 0–100 with higher scores indicating less limitations. (2 items)
Nutritional Status	Body Mass Index	Calculated by measuring height and weight. A low BMI for older adults is <22 kg/m2 and obesity is ≥30 kg/m2. (1 item)
	Unintentional Weight Loss	Unintentional weight loss in the last 6 months. Unintentional weight loss >5% in 6–12 months is associated with increased mortality. (1 item)
Cognition	Blessed Orientation-Memory-Concentration Test*	Measures temporal orientation, short-term memory, and concentration. Weighted score ranges 0-28 with higher scores indicating more impairment. A score >9 is concerning for cognitive impairment. (6 items)
	Montreal Cognitive Assessment*	Measures visuospatial skills, executive functions, memory, attention, calculation, concentration, language, abstraction, and orientation. On a scale of 0-30 with a score <26 indicating cognitive impairment. (16 items)
Medications	Comprehensive list of medications	Participant recorded medication list. Polypharmacy is defined as ≥5 prescribed medications.

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OARS Older Americans Resources and Services, MOS medical outcome study, SF-36 36-item Short Form, TUG timed up and go, BMI body mass index

*Indicates performance-based measures that must be administered by personnel

The 7 domains of the SCD-FA are functional status, comorbid medical conditions, psychological state, social support/social functioning, weight status, cognition, and patient-reported medication list. The oncology geriatric assessment included 3 provider-administered measures: Timed Up and Go (TUG), provider-reported Karnofsky Performance Status (KPS), and the Blessed Orientation Memory Concentration Test. We added 5 provider-administered physical performance measures to the TUG: usual gait speed, 6MWT with heart rate recovery, seated grip strength, 30-second chair stand, and dual-task performance (also includes cognitive component). We compared the results of each physical performance test to normative values based on age and gender where such data were available [22]. We added the Montreal Cognitive Assessment (MoCA) as an additional cognitive measure and the reading subtest of the Wide Range Achievement Test 5^th Edition to account for differences in academic achievement beyond stated education level. For a detailed description of each measure, see Table ​Table11 and published protocol [23].

Administering SCD-FA

Investigators who were SCD physicians received training and ongoing guidance on how to properly perform and analyze the physical function portions of the SCD-FA throughout the study. The SCD-FA was administered by first author and a trained research specialist in a quiet hallway in the sickle cell clinic.

Outcomes

The endpoints of this study are based on Consolidated Standards of Reporting Trials (CONSORT) extension to pilot and feasibility trials guidelines [24, 25].

Primary endpoint

The primary endpoint was the proportion of participants who completed the assessment in its entirety out of those that were consented. We defined feasibility as ≥80% of participants completing the SCD-FA.

Secondary endpoints

The secondary endpoints were proportion consenting, duration of the SCD-FA, adverse events, and acceptability. We defined feasibility for these secondary endpoints as (1) ≥80% providing written consent of those approached to participate, (2) a mean duration for completing the SCD-FA ≤120 min, and (3) no moderate or severe adverse events within 48 h after completing the SCD-FA.

We assessed acceptability of the SCD-FA with a satisfaction survey at the end of each study visit. We included questions about acceptability of the time it took to complete the entire assessment, whether questions were difficult to understand, uncomfortable, or upsetting, and if there were measures that should be added or removed. Acceptability was defined as <20% reporting difficulties in understanding measures or reporting questions as upsetting or uncomfortable and at least 80% reporting the length of the SCD-FA as appropriate.

Feasibility results

Eighty percent of patients approached for the study consented, and 91% of consented participants completed the SCD-FA. The median duration of the assessment was 89 min (IQR 80–98 min), and there were no adverse events during or after the SCD-FA was performed (Fig. ​(Fig.11).

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Fig. 1

Consort diagram. We approached 55 participants for the study, consented 44, removed 4 due to multiple missed study visits, and performed the Sickle Cell Disease Functional Assessment in 20 younger adults and 20 older adults. Reasons participants gave for declining to participate are listed

On the acceptability survey, 95% reported that the length of the SCD-FA was appropriate. One participant found a question upsetting, which was about a history of drug use. Five percent reported that there was at least one item on the questionnaires that was difficult to understand. When asked about feedback on removing items from the SCD-FA, 10% recommended removing the MoCA due to difficulties performing certain portions.

Functional status

Thirteen percent of all participants were dependent in 1 or more ADL/IADL (20% of younger adults vs. 5% of older adults). Only 5% of all participants had a patient-reported KPS <80% and 2.5% had a physician-reported KPS <80% (KPS ≥80% indicates good performance status [30]). There was more variability on the Physical Functioning subscale of the 36-item Short Form Health Survey (SF-36) with a mean score for all participants of 77 (SD = 20) and a range of 25–100 on a scale of 0–100 [31]. Thirteen percent (5) of participants had a fall in the last 6 months (≥1 fall indicates an increased risk of subsequent falls [16]).

The results of the physical performance measures with the expected performance based on normative values for their age and gender and their equivalent functional age is summarized in Table ​Table3.3. For usual gait speed, younger adults had a mean walking speed of 1.10 (SD = 0.22) and older adults had a mean walking speed of 1.14 m/s (SD = 0.15). Usual gait speed by age shown in Fig. ​Fig.22 demonstrates that the majority (63%) of both younger and older males and females had a slow usual gait speed (<1.2 m/s) [32]. Gait speed did not significantly decrease with age. On the TUG, younger adults had a mean time of 9.2 seconds (SD = 2.2 s) and older adults had a mean time of 10.1 s (SD = 1.7). Sixty-eight percent of participants had a slow TUG time >10 s and 10% of participants had a TUG >12 s [33]. Both younger and older adults had a mean TUG time that was longer compared to the general population when stratified for age and gender (Table ​(Table3)3) [22, 27].

Table 3

Results of physical performance measures for younger adults (age 18–49, mean age 30; N = 20) and older adults (age ≥50, mean age 57; N = 20)

		Actual scores Mean ± SD	Performance for healthy norms by age and gender	Equivalent functional age (years)
Gait speed [26] (m/s)	Age 18–49	Male: 1.12 ± 0.23	Males: 1.46 ± 0.9	Males: 80–89
		Female: 1.09 ± 0.23	Female: 1.42 ± 1.3	Females: 80–89
	Age ≥50	Male: 1.09 ± 0.14	Males: 1.36 ± 2.1	Males: 80–89
		Female: 1.19 ± 0.15	Female: 1.30 ± 2.1	Females: 80–89
Timed Up Go [22, 27] (s)	Age 18–49	Male: 8.9 ± 1.6	Males: 8.6 ± 1.2	Males: 70–79
		Female: 9.5 ± 2.8	Females: 8.6 ± 1.2	Females: 70–79
	Age ≥50	Male: 10.7 ± 2.0	Males: 8.0 ± 2	Males: 80–89
		Female: 9.5 ± 1.1	Females: 8.0 ± 2	Females: 80–89
30-second chair stand [28] (#)	Age 18–49	Male: 15 ± 5	Males: N/A	Males: 65–69
		Female: 13 ± 5	Females: N/A	Females: 65–69
	Age ≥50	Male: 10 ± 4	Males: 16 ± 4.3	Males: 85–89
		Female: 12 ± 3	Females: 15 ± 4.0	Females: 75–79
6-min walk [22, 29] (m)	Age 18–49	Male: 585 ± 104	Male: 638 ± 44	Males: 60–69
		Female: 498 ± 118	Female: 593 ± 57	Female: 60–69
	Age ≥50	Male: 465 ± 73	Male: 572 ± 92	Males: 80–84
		Female: 499 ± 64	Female: 538 ± 92	Female: 70–74

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Fig. 2

Usual gait speed (meters/second) by age and gender among individuals with sickle cell disease The figure displays the fastest of 2 usual gait speed trials stratified by age decade. The mean gait speed for all participants was 1.12 m/s (95% CI 1.06, 1.18). The majority of participants (63%) had a gait speed slower than 1.2 m/s (the speed necessary to safely cross the street at an intersection). Twenty-five percent had a gait speed slower than 1 m/s

On the 6MWT younger adults walked a mean distance of 546 meters (SD = 116) and older adults walked a mean distance of 482 meters (SD = 69) (Based on American Society of Hematology guidelines, a 6MWT distance <333 m requires further evaluation for pulmonary hypertension in SCD [34]). On the 30-second chair stand test, younger adults completed a mean of 14 chair stands (SD = 5) and older adults completed a mean of 11 chair stands (SD = 4). For the 6MWT and the 30-second chair stand, younger adults had performance similar to people in their 60s and 70s in the general population and older adults had performance similar to people in their 70s and 80s (Table ​(Table3)3) [22, 28, 29]. There were expected gender difference in seated grip strength with mean maximum grip strength of 26 kg of force (SD 5.8) for younger females, 49 kg (SD 10.7) for younger males, 26 kg (SD 4.3) for older females, and 42 kg (SD 10.9) for older males (Fig. ​(Fig.3)3) [35–37].

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Fig. 3

Maximum seated grip strength by age group and gender in individuals with sickle cell disease. Boxplot of maximum seated grip strength of 3 trials on each hand. Mean grip strength by age group and gender is also represented by the star on each boxplot and compared to mean maximum grip strength normative values by age and gender in the United States published by Hanten et al. [35]

Cognitive functioning

On cognitive testing, the mean MoCA score for all participants was 26 (SD = 3). Thirty-five percent of younger adults and 50% of older adults had a MoCA score consistent with cognitive impairment (score <26 out of 30). When using score <23, which is a suggested optimal cutoff for non-Hispanic African Americans, 15% of younger adults and 25% of older adults had scores <23 [38]. Out of all participants, only 5% (2) had a score greater than 9 (concerning for cognitive impairment) on the Blessed Orientation Memory Concentration Test.

Weight status

The mean body mass index (BMI) for all participants was 26 kg/m² (SD = 5). Eighteen percent had a BMI categorized as obese (≥30 kg/m2) and 18% had a low BMI (<22 kg/m2). Thirteen percent reported having unintentional weight loss in the last 6 months.

Psychosocial measures

There was a wide range of results for the Medical Outcome Study Social Support Survey instrument with a mean score for all participants of 70 (SD = 21) and a range of 7–93 on a scale of 0–100 (with lower scores indicating less support). Older adults had a mean social support score of 72 (SD = 25) and younger adults had a mean score of 69 (SD = 18). Eighteen percent of all participants reported that their health interfered with their social activities at least some of the time in the last month, 35% reported that their social activity decreased in the last 6 months due to their condition, and 38% reported that their social activity was limited compared to their others their age because of their health. On the 18-item Mental Health Inventory (MHI-18), the mean score for all participants was 78 (SD = 14) with a range of 27–100 on a scale of 0–100 (with higher scores indicating better mental health). Younger adults had a mean mental health score of 77 (SD = 16) with a range 27–100, and older adults had a mean score of 79 (SD = 12) with a range 43–97. On the anxiety subscale of the MHI-18, 60% of younger adults and 20% of older adults had a score ≤75. On the depression subscale of the MHI-18, 30% of younger adults and 20% of older adults had a score ≤75.

Limitations

There are limitations to this study. First, there may be a selection bias given that participants are individuals who come to a SCD clinic in an academic center, were willing to participate in research studies, and able to meet the inclusion and steady-state criteria. Secondly, pain and SCD complications that are active at the time of the assessment may interfere with performance. These SCD complications can confound the results of measures, such as physical performance tests and psychosocial measures. Many SCD complications increase with age; therefore, with older participants, it becomes increasingly important to determine how pain and other specific complications affects results [4]. Lastly, there are limitations to interpretation of the results based on normative values available in the literature since many normative studies include few or no African Americans. Also, SCD-specific cut points have not been established. To address this, we have made every effort to compare results to populations that include a more diverse population. During validation of the SCD-FA, we will set cutpoints for individuals with SCD at levels that are predictive of relevant outcomes.

We would like to acknowledge the contribution of the patients who participated in this study. We would like to acknowledge our research specialist, Arvind Mallikarjunan, who assisted with performing the SCD-FA on participants. We would also like to acknowledge Arti Hurria for sharing materials used in the oncology geriatric assessment study; may she rest in peace. We would also like to acknowledge Harvey Cohen for providing advice on focused geriatric assessment and Heather Whitson for providing guidance on selecting geriatric specific measures for this pilot study.