Supplementary material

Methods

Physical frailty (Fried)

Participants were considered to be physically frail if they fulfilled ≥ 2 of 4 frailty criteria described by

Fried (1) (Table 1): unintentional weight loss, exhaustion, low physical activity and reduced handgrip

strength. Unintentional weight loss was defined as weight loss > 5% between round 4 and 5 and the

participant reporting not to be on a diet. Presence of exhaustion was assessed using the following

two statements of the Center for Epidemiologic Studies Depression scale (2) : “ I felt that everything I

did was an effort” and “I could not get going”. Participants answering a ‘moderate amount of the

time (3-4 days)’, or ‘most of the time’ to either of these questions were considered to be exhausted.

Low physical activity was defined as meeting all of the following three criteria: 1) < 10 th percentile of

a physical activity score consisting of low (<4 metabolic equivalents), middle (4-6.5 metabolic

equivalents), and high (>6.5 metabolic equivalents) physical activities and taking into account the

time spent on each activity; 2) <25th percentile of walking hours per week during the last 12 months;

3) failing to meet the Dutch physical activity guideline. Handgrip strength was measured using a

dynamometer (Jamar, Sammons Preston Rolyan). Cut-off points for handgrip strength in kg were

stratified by sex and BMI. Cut-off points for men were ≤29.0 kg for BMI ≤24.0, ≤30.0 kg for BMI 24.1-

26.0, ≤30 kg for BMI 26.1-28.0, and ≤32.0 kg for BMI >28.0. Cut-off points for women were ≤17.0 kg

for BMI ≤23.0, ≤17.3 kg for BMI 23.1-26.0, ≤18.0 kg for BMI 26.1-29.0, and ≤21.0 kg for BMI >29.0.

The cut-off points used for exhaustion and handgrip strength were identical to Fried (1).

Physical frailty (Gobbens)

Participants were considered physically frail according to Gobbens (3) when they fulfilled the

specified requirements for ≥ 4 of the following 8 criteria: exhaustion, unintentional weight loss,

reduced handgrip strength, perceived health, walking, balance, poor hearing, and poor vision (Table

1). Exhaustion, unintentional weight loss, and reduced handgrip strength were measured as

described above for physical frailty (Fried) (1). Limitations in walking due to health were assessed

with a question regarding 100 meter walking. Poor perceived self-reported health were those with a

self-reported health of less than good, on a scale with the following response categories: poor, fair,

good, very good, excellent. The question was taken from the 36-Item Short-Form Health Survey (4,

5). The Tandem Stand Balance Test was used to test balance in participants ≥ 60 years old. Failing or

refusing to do the test, or not being able to keep balance > 10 seconds, was considered a positive

score for this criterium (being < 60 years counted as a negative score). Hearing impairment (present

or absent) was also assessed by self-report, with questions on hearing in general, and experienced

difficulties in group conversations. Vision impairment (present or absent) was assessed in a similar

manner.

Cognitive frailty

Participants were considered cognitively frail when scoring < 10th percentile on global cognitive

functioning (Table 1). Global cognitive functioning was assessed with a neuropsychological test

battery. Memory function, information processing speed and cognitive flexibility were tested using

15 Words Verbal Learning Test (6), the Stroop Color–Word Test (7), the Word Fluency Test (8) and

the Letter Digit Substitution Test (9). Nooyens et al (10) describe the cognitive tests in more detail.

The cognitive tests were performed among participants ≥ 45 years old. Participant < 45 years old

were defined as not being cognitively frail. Cognitive scores were adjusted for level of education and

number of tests performed during follow-up.

Psychological frailty

Psychological frailty was defined as fulfilling both criteria for depression and criteria for general

mental health (Table 1). Depressive symptoms were assessed with 20 questions of the Center for

Epidemiologic Studies Depression scale. Those with a score of ≥16 (out of range of 0-60) were

defined to have a high risk of depression. Mental health status was measured with the Mental Health

Inventory 5 (5). Scores of five questions on a six-point scale were transformed into a total score (11)

ranging from 0 to 100 and a cut-off point of 60 was used to indicate a poor (≤60) mental health status

(12).

Social frailty

Social frailty was defined as meeting ≥ 2 of 3 criteria using the Loneliness scale, Social Support List-12

and a questionnaire about social participation from the Dutch Municipal Health Services Elderly

Monitor (Table 1). A cut-off point of ≥ 9 on the Loneliness scale (11 items with a score 0 or 1) was

used to indicate loneliness (13, 14). A score of < 24 (out of 48) on the 12 item Social Support List was

considered to indicate low social support (15). Finally, Participants in the lowest decile on The Dutch

Municipal Health Services Elderly Monitor (11), a questionnaire regarding social participation used in

the Dutch public health care for elderly people (15 items with a maximum score of 65), were

considered to have little social participation.

Supplementary Table 1. Characteristics table for physical frailty (Gobbens).

Legend: N (%) or mean (SD)

1BMI=body mass index: underweight (< 20 kg/m2), normal weight (20-24.9 kg/m2), overweight (25-29.9 kg/m2), and obesity (≥ 30 kg/m2).2physical activity: meet Dutch physical activity guideline (30 minutes of moderate to vigorous physical activity per day on at least 5 days per week). 3 multimorbidity: having two or more out of diabetes, cancer, myocardial infarction, cerebrovascular accident, and chronic respiratory symptoms.

Variables Physically frail (Gobbens)

(n=108)

N (%) or mean (SD)

Socio-demographic

sex (men) (%) 40 (37.0%)

age (yrs) (SD) 68.7 (9.1)

low level of education (%) 74 (68.5%)

Body composition

BMI1 (kg/m2) (SD) 30.0 (6.9)

underweight (%) 4 (3.7%)

normal weight (%) 25 (23.2%)

overweight (%) 31 (28.7%)

obese (%) 48 (44.4%)

Life-style

current smoker (%) 30 (28.3%)

physical activity2 (%) 46 (42.6%)

Health and disease

poor self-reported health (%) 90 (83.3%)

multimorbidity3 (%) 42 (39.3%)

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Supplementary Figure 1. The association between BMI (round 2) and frailty (round 5) (unadjusted

proportions). Physical frailty (Fried) (A), cognitive frailty (B), psychological frailty (C), and social frailty (D). Note:

In Round 2 the participants were 15 years younger than in Round 5.

Supplementary Figure 2. The association between BMI (round 2) and frailty (round 5) (adjusted proportions).

Physical frailty (Fried) (A), cognitive frailty (B), psychological frailty (C), and social frailty (D). Note: In Round 2

the participants were 15 years younger than in Round 5.