Unexplained functional decline

Unexplained functional decline is a loss of the ability to perform daily activities (mobility, self care, household tasks, work, cognition, social participation) over weeks to months, without a cause evident at first contact.

In older adults it is usually the presenting feature of an acute illness, a drug effect, depression, dementia or frailty.

In adults of any age with chronic disease, malnutrition and weight loss ("adult failure to thrive") fall under this presentation: the picture of weight loss, poor appetite, inactivity, social withdrawal and loss of independence.

Clinical relevance. Decline in function is a sensitive but non specific sign of disease. A new infection, heart failure, anaemia, hypothyroidism, hyponatraemia or a medication can reduce function before any classical symptom appears. Early correction can restore independence; delay leads to deconditioning, falls, pressure injury, institutionalisation and death.

Definitions.

• Basic activities of daily living: bathing, dressing, toileting, transfers, continence, feeding.
• Instrumental activities: shopping, cooking, housework, medications, finances, telephone use, transport.
• Frailty: a state of reduced physiological reserve with vulnerability to minor stressors. Clinical Frailty Scale 1 (very fit) to 9 (terminally ill); 5 or more indicates frailty.
• Sarcopenia: loss of muscle mass with reduced strength (grip strength under 27 kg in men, under 16 kg in women) or performance (gait speed 0.8 m/s or less).
• Adult failure to thrive: weight loss of 5% or more in 6 months, low appetite, low physical activity and cognitive or mood change, with loss of independence.

Classification by tempo. Acute (days, an acute illness or delirium), subacute (weeks), chronic progressive (months, neurodegeneration, malignancy, chronic organ failure).

Classification by domain.

• Physical: weakness, balance or gait failure, pain, breathlessness, fatigue, sensory loss.
• Cognitive and psychiatric: dementia, delirium, depression, anxiety, grief.
• Nutritional: weight loss, poor intake, dysphagia, dental problems.
• Social and environmental: isolation, bereavement, caregiver loss, poverty, housing, abuse, neglect.
• Iatrogenic: drugs, hospitalisation, immobility.

Mechanisms. Reduced reserve in several organ systems means that a small insult tips the person under the threshold for independence. Chronic inflammation (interleukin 6, tumour necrosis factor) drives muscle catabolism, anorexia and fatigue. Immobility causes loss of about 1% to 3% of muscle strength each day of bed rest in older people.

History. (Corroborate with a relative or carer.)

• Which functions are lost, when, in what order, and how fast. Comparison with function 6 and 12 months ago.
• Recent falls, fractures, admissions, surgery, infections, bereavement, change of home or carer.
• Weight, appetite, swallowing, dentition, thirst, bowel and bladder function.
• Symptoms by system: breathlessness, cough, chest pain, palpitations, abdominal pain, urinary symptoms, headache, visual and hearing change, pain, joint and muscle symptoms, sleep.
• Cognition and mood: memory, confusion, hallucinations, personality change, low mood, loss of interest, anxiety, suicidal thoughts.
• Complete drug list including over the counter and traditional remedies: sedatives, anticholinergics, opioids, antihypertensives, diuretics, digoxin, antipsychotics, antiepileptics, polypharmacy (five or more drugs). Alcohol and tobacco.
• Social: living alone, carer strain, finances, food access, safety, abuse, neglect.
• Chronic disease history: heart failure, chronic obstructive pulmonary disease, kidney disease, diabetes, Parkinson disease, cancer, HIV, tuberculosis.
• Goals and preferences, advance care plans.

Examination.

• Vital signs, orthostatic blood pressure, oxygen saturation, temperature, weight, body mass index, mid upper arm circumference.
• Hydration, pallor, jaundice, oedema, lymph nodes, thyroid, breast, rectal examination and prostate where indicated.
• Heart, chest, abdomen (masses, organomegaly, bladder, faecal loading).
• Mouth: dentition, candidiasis, ulcers. Skin: pressure injury, bruising.
• Neurological: gait, balance (timed up and go, over 12 seconds indicates fall risk), power, tone, reflexes, sensation, cranial nerves, tremor, rigidity.
• Cognition (Mini-Cog, Abbreviated Mental Test, Montreal Cognitive Assessment), delirium screen (4AT), mood (Geriatric Depression Scale, PHQ-9).
• Vision and hearing.
• Function: grip strength, gait speed over 4 metres, chair stand test (five stands).

Red flags.

• Acute onset with confusion, fever, hypotension or tachypnoea (sepsis, delirium).
• Rapid weight loss, night sweats, haemoptysis, dysphagia, change in bowel habit, new lumps (malignancy, tuberculosis).
• Focal neurological signs, new headache, gait change with incontinence (stroke, subdural haematoma, normal pressure hydrocephalus).
• Chest pain, new breathlessness, syncope.
• Suicidal ideation.
• Signs of abuse or neglect.
• Severe hyponatraemia, hypercalcaemia, uraemia or hypoglycaemia on tests.

Acute illness presenting atypically. Pneumonia, urinary tract infection, sepsis, myocardial infarction, heart failure, pulmonary embolism, stroke, acute abdomen, acute kidney injury, faecal impaction, urinary retention, fracture, pain.

Infection. Tuberculosis, HIV, endocarditis, abscess, osteomyelitis, hepatitis, chronic urinary infection, pressure injury sepsis, COVID-19 and other viral illness.

Cardiorespiratory. Heart failure, aortic stenosis, arrhythmia, chronic obstructive pulmonary disease, interstitial lung disease, pulmonary hypertension, anaemia.

Metabolic and endocrine. Hypothyroidism, hyperthyroidism (apathetic form), diabetes mellitus (hyper and hypoglycaemia), adrenal insufficiency, hyponatraemia, hypercalcaemia, hypokalaemia, vitamin B12 and folate deficiency, vitamin D deficiency, chronic kidney disease, chronic liver disease, malnutrition.

Neurological. Dementia (Alzheimer, vascular, Lewy body, frontotemporal), delirium, Parkinson disease and atypical parkinsonism, normal pressure hydrocephalus, subdural haematoma, stroke, peripheral neuropathy, myopathy, motor neurone disease, cervical or lumbar myelopathy, epilepsy.

Psychiatric. Depression, anxiety, psychosis, alcohol or substance use disorder, grief, apathy.

Malignancy. Solid organ tumours, haematological malignancy, metastatic disease, paraneoplastic syndromes.

Musculoskeletal. Osteoarthritis, osteoporotic fracture, polymyalgia rheumatica, giant cell arteritis, rheumatoid arthritis, sarcopenia, osteomalacia, foot disease.

Sensory. Visual loss (cataract, macular degeneration, glaucoma), hearing loss.

Drugs. Sedatives, benzodiazepines, opioids, anticholinergics, antipsychotics, antihypertensives with hypotension, diuretics with dehydration or electrolyte loss, digoxin toxicity, beta blockers, statins with myopathy, polypharmacy.

Social. Isolation, neglect, abuse, poverty, malnutrition from food insecurity.

1. Assess function with a validated tool (Barthel index, Katz index, Lawton scale) and establish the time course. Rule out delirium, sepsis and acute illness first.
2. First line tests: full blood count with film, ESR and C reactive protein, urea, creatinine and electrolytes (sodium, potassium), calcium (corrected), phosphate, magnesium, liver function tests, albumin, glucose or HbA1c, thyroid stimulating hormone, vitamin B12, folate, ferritin, 25 hydroxyvitamin D, creatine kinase, urinalysis, and urine culture if symptomatic.
3. ECG, chest radiograph, oxygen saturation. Natriuretic peptide if heart failure is suspected.
4. Infection screen as indicated: blood cultures, HIV test with consent, sputum for acid fast bacilli and tuberculosis polymerase chain reaction, hepatitis serology.
5. Cognitive and mood testing; delirium resolves in days to weeks and should be reassessed after acute illness.
6. Malignancy search directed by symptoms and age appropriate screening: CT of chest, abdomen and pelvis when weight loss is unexplained, faecal immunochemical testing, endoscopy, mammography, PSA with counselling, serum protein electrophoresis and free light chains.
7. Brain imaging (CT or MRI) when there are focal signs, new cognitive change, falls with head injury, or gait disturbance with incontinence.
8. Nutritional assessment (Malnutrition Universal Screening Tool or Mini Nutritional Assessment, body mass index, albumin only as a marker of inflammation).
9. Swallow assessment, dental review, hearing and vision tests.
10. Full geriatric assessment covering medical, functional, cognitive, psychological, social and environmental domains.

Limits. Many older adults have several contributing causes at once. Albumin and weight are poor sole measures of nutrition. Cognitive screening tests are unreliable during delirium or depression. A single normal test round does not rule out a progressive process; review at 4 to 6 weeks.

Immediate. Treat sepsis, hypoxia, hypoglycaemia, dehydration, urinary retention and faecal impaction. Stop or reduce harmful drugs. Control pain.

Cause directed treatment.

• Delirium: find and treat the trigger, reorientation, sleep protection, hydration, glasses and hearing aids, mobilisation. Haloperidol 0.5 mg orally or intramuscularly (repeated after 1 hour; maximum 3 mg in 24 hours in older adults) only for distress or danger to others, avoiding it in Parkinson disease and Lewy body dementia.
• Infection: tuberculosis regimen isoniazid 5 mg/kg (maximum 300 mg), rifampicin 10 mg/kg (maximum 600 mg), pyrazinamide 25 mg/kg (maximum 2 g) and ethambutol 15 mg/kg daily for 2 months, then isoniazid and rifampicin for 4 months, with pyridoxine 10 mg daily. Other infections directed by site and organism.
• Hypothyroidism: levothyroxine 1.6 micrograms/kg orally once daily on an empty stomach; start 25 micrograms daily in older adults or coronary disease and increase every 4 to 6 weeks.
• Adrenal insufficiency: hydrocortisone 15 to 25 mg daily in divided doses; in crisis 100 mg intravenously then 200 mg over 24 hours.
• Depression: sertraline 25 mg orally daily for a week then 50 mg (maximum 200 mg) or mirtazapine 15 mg at night (maximum 45 mg), with psychological therapy; monitor sodium at 2 and 4 weeks in older adults.
• Anaemia and deficiencies: iron (ferrous sulphate 200 mg once daily or on alternate days), hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks then every 3 months, folic acid 5 mg daily for 4 months, colecalciferol 800 to 2,000 units daily (or 50,000 units weekly for 6 to 8 weeks for deficiency).
• Heart failure, chronic obstructive pulmonary disease, kidney disease, diabetes: optimise disease control and adjust drugs for kidney function.
• Parkinson disease: levodopa with carbidopa, increasing from 50 mg/12.5 mg three times daily as directed by neurology.
• Dementia: structured routine, carer support, safety review, cholinesterase inhibitor (donepezil 5 mg at night, increased to 10 mg after 4 to 6 weeks) in Alzheimer disease and Lewy body dementia.
• Polymyalgia rheumatica: prednisolone 15 mg daily with slow taper.
• Normal pressure hydrocephalus and subdural haematoma: neurosurgical referral.
• Polypharmacy: stop drugs without clear benefit, one change at a time, remove anticholinergics and sedatives, and review antihypertensives for orthostatic hypotension.

Nutrition. Dietary assessment, fortified diet, small frequent meals, oral nutritional supplements (1.5 to 2 kcal/mL, 2 to 3 servings daily) for malnutrition, dental treatment, treatment of dysphagia (texture modified diet), protein 1.0 to 1.2 g/kg daily, and enteral feeding only after a goals of care discussion.

Rehabilitation. Physiotherapy and occupational therapy (strength and balance training 3 times weekly for 12 weeks, mobility aids, home adaptations), early mobilisation, and falls prevention. Vitamin D and calcium. Review vision and footwear.

Monitoring. Reassess function and weight at 2 to 4 weeks, repeat blood tests at 4 to 6 weeks, and review medicines at each visit.

Referral and escalation. Geriatric medicine for full assessment. Neurology, psychiatry, oncology, cardiology or respiratory medicine as the cause emerges. Palliative care when decline is progressive and irreversible. Social services for carer support and safeguarding.

Admission. Sepsis, delirium with acute illness, inability to mobilise or care for self safely, severe electrolyte or glucose abnormality, acute neurological change, safeguarding concern, or unsafe discharge.

Safety netting. Return for new confusion, falls, fever, inability to eat or drink, chest pain, breathlessness, black stool, urinary retention, or if carers cannot cope.

Special groups. Older adults: frailty and geriatric assessment. Younger adults: HIV, tuberculosis, depression, substance use, endocrine disease and malignancy are leading causes. Children with failure to thrive need paediatric growth assessment, feeding history and screening. HIV and tuberculosis endemic regions: test early. End of life: discuss goals of care, advance care plans and resuscitation preferences.