Mild Cognitive Impairment

Mild cognitive impairment is a measurable decline in one or more cognitive domains that is greater than expected for age and education, with preserved independence in daily activities. It may be an early stage of Alzheimer disease, Lewy body disease or vascular disease, or it may be caused by a reversible condition.

The prevalence is about 15 to 20% in people over 60 years, rising with age. About 10 to 15% each year progress to dementia in specialist clinics, and some people revert to normal.

Subtypes. Amnestic (memory predominant, often Alzheimer disease), non-amnestic (executive, language or visuospatial), single domain or multiple domain.

Risk factors. Age, APOE e4 allele, hypertension, diabetes, hearing loss, depression, social isolation, physical inactivity, obesity, smoking, alcohol excess and head injury.

Pathophysiology.

Early neurodegenerative or vascular change causes network dysfunction in the medial temporal and frontoparietal regions before function is lost.

Amyloid and tau accumulation, small vessel disease and Lewy body pathology are the commonest substrates.

• A concern about cognition raised by the patient, an informant or the clinician, usually memory lapses, word finding difficulty or poor planning.
• Objective impairment on testing, usually 1 to 1.5 deviations under the mean score for age.
• Daily function essentially intact, with minor trouble with complex tasks (finances, medicines).
• Mood and sleep change, anxiety or apathy; REM sleep behaviour disorder or hyposmia in prodromal Lewy body disease.

Red flags.

• Rapid decline over weeks to months, or onset under 65 years.
• Focal neurological signs, seizures, gait disorder or incontinence early.
• Prominent behavioural or language change, or hallucinations.
• Cancer history, immunosuppression or a toxic exposure.

• Cognitive screening (Montreal Cognitive Assessment or similar) followed by detailed neuropsychological testing; informant history of function.
• Screen for depression, anxiety, sleep apnoea, delirium and drug effects (anticholinergics, benzodiazepines, opioids).
• Blood tests: full blood count, electrolytes, calcium, renal, liver and thyroid function, B12, folate, glucose and HbA1c; HIV and syphilis serology when risk is present.
• MRI of the brain (atrophy pattern, vascular change, other causes); FDG-PET, amyloid PET or cerebrospinal fluid or plasma biomarkers (amyloid and tau) in selected patients to define Alzheimer disease.
• Hearing and vision assessment; EEG when seizures or encephalitis are possible.

Differential diagnosis. Normal ageing, depression, delirium, early dementia, medication effects, sleep disorders, hypothyroidism, B12 deficiency, subdural haematoma, normal pressure hydrocephalus and alcohol related cognitive impairment.

• Treat reversible contributors: depression, sleep apnoea, hearing loss, B12 deficiency, thyroid disease and drugs with anticholinergic or sedative effects.
• Vascular risk control: blood pressure under 130/80 mmHg, glucose and lipid control, stop smoking and limit alcohol.
• Lifestyle: aerobic exercise (150 minutes each week), cognitive and social engagement, a Mediterranean style diet and hearing aids when needed.
• Cholinesterase inhibitors and memantine have no benefit in mild cognitive impairment and are not used.
• Early Alzheimer disease with confirmed amyloid pathology: lecanemab 10 mg/kg intravenously over about 1 hour every 2 weeks, given by a specialist centre. Maximum 10 mg/kg each infusion. Monitor with MRI before the 5th, 7th and 14th infusions for amyloid related imaging abnormalities, and for infusion reactions. APOE e4 testing before treatment because homozygotes have a higher risk of oedema and haemorrhage. Avoid with anticoagulants, a history of large haemorrhage, multiple microhaemorrhages on MRI, and in pregnancy; no renal or hepatic adjustment. Availability and funding vary.
• Donanemab is an alternative: 700 mg intravenously every 4 weeks for the first 3 doses, then 1400 mg every 4 weeks. Maximum 1400 mg each infusion. Monitor MRI before the 2nd, 3rd, 4th and 7th infusions and for infusion reactions. Avoid with anticoagulants, a history of large haemorrhage and multiple microhaemorrhages on MRI, and in pregnancy. Availability and funding vary.
• Treat depression: sertraline 50 mg orally once daily, increased by 50 mg every 1 to 2 weeks as needed to 100 to 200 mg daily. Maximum 200 mg daily. Continue for at least 6 to 12 months after remission. Monitor mood and suicidal thoughts, sodium, bleeding and serotonin toxicity. Reduce dose (or use alternate days) in hepatic impairment; no renal adjustment; avoid with monoamine oxidase inhibitors.
• Plan ahead: capacity, driving review, medicines support and advance care discussion.

Monitoring. Reassess at 6 to 12 months with repeat cognitive testing; earlier if function falls.

Referral and escalation. Memory clinic for atypical features, young onset, rapid decline or biomarker testing; geriatric or psychiatric services as needed.

Special groups. Older adults: review polypharmacy. People with Down syndrome: baseline cognitive records and yearly screening.