Mild cognitive impairment — evaluation, treatment and outcome

Definition and criteria. MCI is (i) a subjective disorder of memory and/or other cognitive domains, (ii) objective impairment of memory and/or other cognitive domains, and (iii) no significant impact on activities of daily living — so patients do not meet criteria for dementia. The NIA-AA core clinical criteria are concern about a change in cognition (from patient, informant or clinician), impairment in one or more cognitive domains greater than expected for age and education, preservation of independence in functional abilities (mild difficulty with complex tasks is allowed, with minimal aids), and not demented. No thresholds are defined for the degree of impairment. The DSM-5 equivalent is mild neurocognitive disorder.

Clinical evaluation. History from both patient and an informant, focused on the impact on usual activities, lifestyle, the history of the cognitive disorder, and above all whether functional decline has occurred — the point that separates MCI from dementia. Old age alone does not cause cognitive impairment severe enough to render a person dysfunctional, so decline must not be dismissed as ageing.

Cognitive and functional testing. A standardised mental status test plus neuropsychological testing, which is especially useful when the mental status score is normal but function or behaviour has changed (high baseline intelligence) or the score is low without functional deficit (low educational level), and for differentiating depression from dementia. Function is documented with Lawton IADL and basic ADL scales; mood with the Geriatric Depression Scale.

Exclude the treatable — the same three questions used for any confusional presentation. (i) Has the onset been acute (hours to days)? (ii) Are there physical factors — medical illness, sensory deprivation, drugs? (iii) Are psychological factors — depression, psychosis — contributing? Investigate with complete blood count, glucose, blood urea, electrolytes (mEq/L), calcium and phosphorus (mg/dL), liver function tests, TSH (µIU/mL), vitamin B12 (pg/mL), syphilis and HIV serology if suspected, and CT or MRI head where indicated. MCI is heterogeneous and may be due to AD, other neurodegenerative disease, depression, vascular lesions or traumatic brain injury.

Biomarkers where available. NIA-AA research criteria stratify by amyloid markers (CSF Aβ42, amyloid PET) and neuronal injury markers (CSF total tau and p-tau, MRI atrophy, FDG-PET/SPECT hypometabolism): “high likelihood” MCI due to AD = both positive; “intermediate likelihood” = one positive with the other untested; “unlikely due to AD” = both negative. The IWG criteria for prodromal AD require abnormal CSF Aβ1-42 and tau or an abnormal amyloid PET (IWG-2). Most countries, including India, lack national guidelines on biomarker use, which limits harmonisation.

Treatment. No intervention has classically been shown to prevent progression to dementia, and cholinesterase inhibitors are not licensed for MCI. Management therefore centres on: an informed discussion of diagnosis and prognosis with arrangements for ongoing review and support; treating contributory conditions — depression with citalopram, sertraline or mirtazapine (minimal cognitive side effects), hypothyroidism, B12 deficiency, sleep apnoea and alcohol excess; withdrawing anticholinergic and other cognition-impairing drugs; controlling vascular risk factors, especially hypertension, which may favourably influence the course of both degenerative and vascular cognitive impairment; and physical activity and multicomponent exercise, the intervention with the most promising evidence (FINGER positive for multidomain intervention; MAPT largely negative). Add cognitive training, driving and safety assessment, and advance planning.

MCI due to AD has become a treatable, biomarker-defined diagnosis. Lecanemab (FDA full approval July 2023, CLARITY-AD) and donanemab (FDA approval July 2024, TRAILBLAZER-ALZ 2) are licensed specifically for MCI due to AD or mild AD dementia with confirmed amyloid pathology, requiring APOE genotyping and serial MRI for amyloid-related imaging abnormalities (ARIA), with the EMA restricting use to non-APOE ε4 homozygotes. Confirmation of amyloid is now possible by blood: the FDA cleared the Lumipulse G pTau217/Aβ1-42 plasma ratio in May 2025 for symptomatic adults aged 55 and over, and the Alzheimer’s Association Clinical Practice Guideline (2025) endorses blood biomarkers in patients with objective cognitive impairment including MCI — as a triaging test at ≥90% sensitivity and ≥75% specificity, or as a substitute for amyloid PET or CSF at ≥90% for both. US POINTER (2025) confirmed benefit from structured multidomain lifestyle intervention in at-risk older adults.