What is the diagnostic approach for a geriatric patient presenting with symptoms of Alzheimer's disease and dementia, considering their medical history and potential comorbidities such as hypertension, diabetes, and cardiovascular disease?

How to Diagnose Alzheimer's Disease and Dementia

Diagnose Alzheimer's disease and dementia through a structured six-step evaluation that includes obtaining collateral history from an informant, administering validated cognitive testing (MoCA preferred), assessing functional decline in daily activities, performing targeted laboratory testing and brain MRI, and considering AD biomarkers when diagnostic uncertainty persists after initial evaluation. 1, 2

Step 1: Obtain Detailed History from Patient AND Informant

You must interview both the patient and a reliable informant (family member or close friend) together and separately, as patients with dementia often lack insight into their cognitive changes (anosognosia). 1, 3

Key Historical Elements to Document:

• Cognitive changes: Memory problems, word-finding difficulties, getting lost in familiar places, difficulty with complex tasks 1
• Temporal pattern: Gradual onset over months to years (not sudden over hours/days), with clear-cut worsening over time 1
• Functional decline: Specific changes in instrumental activities of daily living (IADLs) including medication management, financial management, driving/transportation, household tasks, cooking, and shopping 1, 2, 3
• Behavioral/neuropsychiatric symptoms: Depression, apathy, agitation, delusions, hallucinations, sleep disturbances—these often precede cognitive symptoms 1
• Sensory and motor function: Gait changes, parkinsonism, visual problems 1

Use structured instruments: AD8 questionnaire or Alzheimer's Questionnaire to systematically capture longitudinal decline 2, 3

Step 2: Perform Objective Cognitive Testing

Administer the Montreal Cognitive Assessment (MoCA) rather than MMSE, as MoCA is superior for detecting mild cognitive impairment and early dementia due to comprehensive assessment of executive functions and visuospatial abilities. 2, 3

• MoCA scores: <26/30 suggests cognitive impairment 2
• Alternative rapid screening: Mini-Cog (3-item recall plus clock draw) takes <3 minutes; scores <3 indicate possible dementia 3

If examination is inconclusive despite symptoms, refer for formal neuropsychological testing to definitively establish whether dementia is present. 2, 4

Step 3: Assess Functional Status with Structured Tools

Document specific functional impairments using validated instruments: Pfeffer Functional Activities Questionnaire (FAQ) or Disability Assessment for Dementia (DAD). 2, 3

Key distinction for diagnosis:

• Mild Cognitive Impairment (MCI): Objective cognitive impairment with preserved independence in functional abilities 1
• Dementia: Cognitive impairment severe enough to interfere with independence in daily activities 1

Step 4: Exclude Reversible Causes and Contributing Factors

Order Tier 1 laboratory testing systematically before attributing symptoms to neurodegenerative disease: 2, 3

• Complete blood count with differential
• Comprehensive metabolic panel
• Thyroid function tests (TSH)
• Vitamin B12, folate, homocysteine levels
• Consider: RPR/VDRL (syphilis), HIV testing in appropriate populations

Review ALL medications for cognitive contributors: anticholinergics, benzodiazepines, opioids, antihistamines, muscle relaxants. 2, 3

Screen for conditions that exacerbate cognitive symptoms: 1

• Depression (use PHQ-9 or Cornell Scale for Depression in Dementia) 3
• Obstructive sleep apnea
• Excessive alcohol consumption
• Delirium superimposed on dementia

Step 5: Obtain Structural Neuroimaging

Order brain MRI (preferred over CT) in the following situations: 2, 3

• Cognitive symptoms began within the last 2 years
• Unexpected or rapid decline in cognition or function
• Recent significant head trauma
• Age <65 years at symptom onset
• Focal neurological signs on examination

MRI is superior to CT for detecting vascular lesions, regional atrophy patterns (medial temporal/hippocampal atrophy in AD), white matter hyperintensities, and alternative diagnoses (tumor, subdural hematoma, normal pressure hydrocephalus). 2, 5

Step 6: Establish Diagnostic Formulation

Integrate findings to determine three diagnostic levels: 1, 2

A. Cognitive Functional Status:

• Cognitively unimpaired
• Mild Cognitive Impairment (MCI)
• Dementia

B. Cognitive-Behavioral Syndrome:

Most common AD presentation is amnestic (impaired learning and recall of recently learned information, plus deficits in at least one other cognitive domain). 1

Non-amnestic presentations include: 1

• Language variant (word-finding difficulties)
• Visuospatial variant (object agnosia, impaired face recognition, getting lost)
• Executive dysfunction variant (impaired reasoning, judgment, problem-solving)

C. Etiological Diagnosis:

Probable AD dementia requires: 1

• Gradual onset over months to years
• Clear-cut worsening of cognition
• Prominent cognitive deficits in pattern described above
• Absence of substantial cerebrovascular disease, Lewy body features, frontotemporal dementia features, or other active neurological disease

Critical caveat: In patients >80 years old, mixed etiology dementia is the rule, not the exception—most harbor multiple brain pathologies (AD + vascular changes + other neurodegenerative diseases). 1, 5 These patients present with atypical or non-amnestic symptoms. 1, 5

Step 7: Consider AD Biomarker Testing (When Indicated)

Order biomarker testing when clinical diagnostic uncertainty persists after completing the above evaluation. 2

Biomarker Options:

Cerebrospinal fluid (CSF) analysis via lumbar puncture: 1, 2

• Measures amyloid-beta (Aβ42/40 ratio), phosphorylated tau (p-tau 217, p-tau 181), total tau
• Sensitivity: 85-90%, Specificity: 80-84% for AD pathology 2

Amyloid PET imaging: 1, 2

• Directly visualizes amyloid plaques in brain
• Sensitivity: 89-98%, Specificity: 88-100% against autopsy 2

Plasma biomarkers (emerging): p-tau 217, p-tau 181, Aβ42/40 ratio 1

Biomarker interpretation for AD likelihood: 1

• High: Both amyloid (A+) and tau/neurodegeneration (T+/N+) biomarkers positive
• Intermediate: One positive, one negative, or one untested
• Low: Both amyloid and tau/neurodegeneration biomarkers negative

Molecular biomarker confirmation is necessary for consideration of new disease-modifying therapies (anti-amyloid monoclonal antibodies like aducanumab, lecanemab). 1

Special Considerations for Geriatric Patients with Comorbidities

In patients with hypertension, diabetes, and cardiovascular disease, strongly consider mixed Alzheimer's and vascular dementia. 5

Imaging findings suggesting mixed pathology: 5

• MRI showing both medial temporal/cortical atrophy (AD pattern) AND white matter hyperintensities, lacunar infarcts, or microbleeds (vascular pattern)
• Elevated Aβ42/40 ratio (atypical for pure AD, suggests mixed pathology) 5

Aggressively manage vascular risk factors as this can slow progression: 5

• Target HbA1c <7.5% (avoid hypoglycemia)
• Initiate/optimize statin therapy (LDL <100 mg/dL)
• Control hypertension
• Screen for atrial fibrillation (obtain ECG)

Common Pitfalls to Avoid

Do not diagnose probable AD dementia when: 1

• Substantial cerebrovascular disease present (stroke temporally related to cognitive decline, multiple infarcts, severe white matter disease)
• Core Lewy body features present (visual hallucinations, parkinsonism, REM sleep behavior disorder, fluctuating cognition)
• Prominent behavioral/personality changes suggesting frontotemporal dementia
• Rapid progression suggesting prion disease

Do not miss depression mimicking or coexisting with dementia: More than half of patients who develop MCI/dementia had depression or irritability symptoms beforehand. 1 Always screen systematically. 3

Do not rely on patient self-report alone: Anosognosia is common; informant history is essential for accurate diagnosis. 1, 3

Longitudinal Monitoring Strategy

Schedule follow-up visits every 6-12 months for stable patients, every 3-4 months if behavioral symptoms or rapid decline. 3

At each visit, reassess: 3

• Cognitive function (repeat MoCA/MMSE)
• Functional status (FAQ/DAD)
• Behavioral symptoms (NPI-Q)
• Caregiver burden
• Medication review
• Nutritional status

Repeat MRI in 12-18 months to assess for new infarcts or progression of white matter disease, or sooner if acute cognitive decline or new focal neurological symptoms. 5