Twenty Six

Question 1

What is a subjective definition of frailty? Objective? IANA?

Answer 1

1. Subjective: A syndrome in which a person under stressful

conditions is at increased risk of being able to carry out essential

activities of daily living (ADL’s), i.e., becomes disabled. It should

be distinguished from disability and as such can be considered to

be pre-disability.

2. Objective (Fried et al., J Gerontol (2001;56A:M146)

 Weight Loss (10 lbs in 1 year) 
 Exhaustion (self-report) 
 Weakness (grip strength – lowest 20%) 
 Walking speed (15 feet – slowest 20%) 
 Low physical activity (Kcals/week – lowest 20%) 

3. IANA definition:

Fatigue

Resistance (1 flight of stairs)

Aerobic (walk one block)

Illnesses (>5)

Loss of weight (5% in 1 year).

Question 2

What are basic ADLs? Instrumental?

Answer 2

Basic (Katz): Transfer, toilet, bathe, dress, eat, continence

Instrumental (Lawton): Shopping, cooking, finances, household activities, Telephone

Question 3

Describe the natural history (steps) of frailty? Outcomes?

Answer 3

Frailty → ↓ Mobility → ↓ Social Activity → ↑ Falls → ↑ Fear of Falling → ↓↓ Mobility → Incontinence

Outcomes: ↓ function; hip fracture; hospitalization; institutionalization; death

Question 4

What are 8 causes of frailty?

Answer 4

1. Decreased food intake
2. Excess Muscle Loss (Sarcopenia)
3. Decline in Executive Function
4. Decline in Balance
5. Diseases, eg., Congestive Heart Failure, Diabetes, Anemia, COPD, Polymyalgia Rheumatica
6. Pain
7. Iatrogenesis (Polypharmacy)
8. Elder Abuse

Question 5

What are anorexia and weight loss associated with? How can they be detected early? What is the anorexia of aging? What are some causes?

Answer 5

1. Anorexia and weight loss lead to death in older persons. Also associated with increased hip fractures, anemia, fatigue, pressure ulcers and immune dysfunction
2. Two scales S.N.A.Q. and MiniNutritional Assessment (MNA) are useful to detect early problems (see appendix)
3. There is a physiological weight loss that occurs with aging. It is called the anorexia of aging.
4. Age-related causes of the anorexia of aging include:

i. Decreased taste and smell
ii. Alterations in fundal compliance and gastric emptying
iii. ↑ cholecystokinin
iv. ↑ leptin (due to low testosterone in males)
v. ↑ cytokines (due to increased fat and subclinical disease)

Question 6

MEALS ON WHEELS? Other causes?

Answer 6

Medications (e.g., digoxin, theophylline, cimetidine)

Emotional (e.g., depression)

Alcoholism, elder abuse, anorexia tardive

Late life paranoia

Swallowing problems

Oral factors

Nosocomial infections (e.g., tuberculosis)

Wandering and other dementia related factors

Hyperthyroidism, Hypercalcemia, Hypoadrenalism

Enteral problems (e.g., gluten enteropathy)

Eating problems

Low salt, low cholesterol and other therapeutic diets

Stones (cholecystitis)

The major other causes of weight loss are dehydration, cachexia (due to marked

excess cytokines (TNFα, IL-6 from conditions such as cancer, CHF, COPD, and

renal and liver failure) and sarcopenia.

Question 7

What is sarcopenia? When is it clinically significant?

Answer 7

Definition: Age-related loss of muscle mass. Myosteatosis refers to age related increase

of fat within muscle. Clinically significant sarcopenia is defined as 2 standard deviations

below the mean appendicular muscle mass of healthy young persons.

Question 8

What is sarcopenic obesity?

Answer 8

Sarcopenic Obesity or “Fat Frail”: These are persons who are overweight but have also

lost muscle mass. Most obese persons have a greater muscle mass than thin persons.

Obese sarcopenia is a better predictor of future disability and mortality than is non-obese

sarcopenia.

Question 9

What are some causes of sarcopenia?

Answer 9

Causes of Sarcopenia:

Low birth weight

Low physical activity

Low testosterone (androgens) (males > females)

Low IGF-1 (insulin growth factor-1) and low Mechanogrowth factor

Low Vitamin D (<30 ng/ml)
\
Low protein intake perhaps especially creatine and branch chain aminoacids

Increased cytokines

Motor unit loss (?↓ Ciliary Neurotrophic Factor)

Peripheral Vascular Disease

? Excess myostatin

Question 10

Describe the biochem of sarcopenia.

Answer 10

Muscle cells live a Ying-Yang existence where hypertrophy and repair (satellite cells) balance atrophy and apoptosis.

Anabolic agents (GH, testosterone, IGF-1) drive the AKT-mTOR system which in conjunction with amino acids leads to protein synthesis and inhibits the atrophy system 
by phosphorylating FOXO and thus inhibiting it from activating atrogin.

Cell atrophy occurs when caspase 3 cleaves actomysin to actin and myosin which then are transported by ubiquitins to the Proteasome (cell death chamber) to be chopped into small peptides and aminoacids. This system is controlled by Atrogin I and MURF I. MURF I is activated by cytokines.

Muscle regeneration occurs when myogenic stem cells are diverted from becoming adipocytes and become satellite cells. This system is driven by testosterone and MGF and inhibited by myostatin.

Question 11

What is the treatment of sarcopenia?

Answer 11

1. Exercise (resistance)
2. Increased protein intake
3. Anabolic agents. Future may be Selective Androgen Receptor Molecules (SARMS) such as Ostarine
4. ? Myostatin antagonists, e.g., Peptobodies
5. Vitamin D