Erfan Bashar
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Alzheimer Disease — Diagnosis

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Educational scope notice: This is a study note for medical students, not medical advice, diagnosis, or treatment guidance. Clinical management should follow local protocols and current guidelines.

Diagnosing Alzheimer disease is a two-part challenge. Recognising dementia in a clearly impaired patient is straightforward. Detecting disease early enough to matter is the real problem. Pathology accumulates for over a decade before symptoms appear. Bedside assessment identifies disease late. Biomarkers identify it early.

The three core diagnostic requirements

All three must be met:

  1. Cognitive or behavioural symptoms that interfere with function. Not just a low test score but real-world decline: failing finances, cooking, dressing, or navigation.
  2. Decline from the patient’s previous level, not explained by delirium or major psychiatric disorder. Acute confusion in an ill elderly patient may be delirium. Withdrawn cognitive slowing may be pseudodementia from depression. Both are potentially reversible. Alzheimer decline is progressive and insidious.
  3. Objective impairment in at least two cognitive domains: memory, executive function, visuospatial abilities, language, and personality or behaviour. A single-domain deficit is not enough.

Collateral history from a caregiver or knowledgeable informant is essential throughout. Patients often lack awareness of their own decline.

The Mini-Mental State Examination

The MMSE is a 30-point bedside scale covering seven areas. Orientation (10 points) tests time then place. Temporal orientation fails first in Alzheimer disease. Registration (3 points) asks immediate repetition of three words. It tests encoding itself. Attention and calculation (5 points) uses serial sevens or spelling a word backwards.

Recall (3 points) asks for the three words after several minutes. It is the single most sensitive item for Alzheimer disease. It directly tests hippocampal memory formation. Language (8 points) covers naming, repetition, commands, and writing. Construction (1 point) asks the patient to copy intersecting pentagons. It tests parietal visuospatial function.

A score of 23 or below out of 30 suggests cognitive impairment, adjusted for education level. Approximate score bands run 24–30 normal, 20–23 mild, 13–20 moderate, and below 12 severe. Band boundaries vary between sources and shift with schooling, so they guide rather than classify. Alzheimer patients lose roughly 2–4 points per year.

A single low score never diagnoses dementia on its own. The criteria additionally require functional decline. A patient scoring 20 who still manages finances and navigates independently has mild cognitive impairment, not dementia.

The Montreal Cognitive Assessment (MoCA) is more sensitive for mild cognitive impairment. It detects executive dysfunction better. It is increasingly preferred for screening. The MMSE remains the more widely taught bedside instrument.

Biomarkers: detecting disease before symptoms

CSF biomarkers form the Alzheimer signature. Aβ42 falls because amyloid is pulled out of the CSF into brain plaques. Low CSF Aβ42 therefore marks brain amyloid burden. Total tau rises with the rate of neuronal death. Phosphorylated tau (p-tau) is more specific because it reflects tangle pathology rather than non-specific injury. The combined pattern — Aβ42 down, tau up, p-tau up — identifies Alzheimer pathology. An Aβ42/tau ratio improves accuracy.

Amyloid PET directly visualises cortical amyloid deposition. It confirms pathology even in preclinical stages. FDG-PET measures glucose metabolism as a proxy for neuronal activity. Alzheimer disease produces temporoparietal hypometabolism with relative sparing of occipital lobe and motor cortex. The pattern helps separate it from frontotemporal dementia (frontal and anterior temporal hypometabolism) and Lewy body dementia (occipitoparietal hypometabolism).

Structural MRI shows medial temporal lobe atrophy, particularly hippocampal volume loss, with posterior cingulate thinning. MRI also rules out mimics: tumours, vascular lesions, normal-pressure hydrocephalus, and subdural collections.

The diagnostic workflow in practice

  1. Clinical assessment. History from patient and caregiver, neurological examination, MMSE or MoCA.
  2. Structural imaging (MRI preferred; CT where MRI is impossible). Imaging excludes structural mimics and demonstrates characteristic atrophy.
  3. Biomarkers when atypical or early. CSF Aβ42/tau or amyloid PET adds value with atypical presentations. It also helps with differentials including frontotemporal or Lewy body dementia, or MCI where prognosis matters. MCI with positive amyloid PET carries a high probability of progression within years.
  4. FDG-PET where the Alzheimer versus frontotemporal distinction stays unclear after structural imaging and CSF.

Evidence anchors

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