Screening Tests for Asymptomatic Relatives of Alzheimer's Patients
For an asymptomatic patient with a relative diagnosed with Mixed Alzheimer's disease, routine neuroimaging such as CT head is not recommended as a screening tool. The focus should be on cognitive screening starting at age 55-65, with basic labs to exclude reversible causes, but structural brain imaging is reserved for when cognitive impairment is actually detected or when atypical features are present.
Age to Begin Cognitive Screening
Begin standardized cognitive screening at age 55 if there is a strong family history of early-onset Alzheimer's disease in first-degree relatives. 1 For individuals without such high-risk features, screening can reasonably begin at age 65. 1
- Blood biomarker tests for amyloid pathology are recommended for triaging in primary care only for patients aged ≥55 years, as most AD biomarkers have not been well studied in younger populations. 1
- Patients younger than 55 years could be tested if suspicion for amyloid pathology is high due to a family history of early-onset AD dementia in first-degree relatives. 1
- For confirmatory testing, age ≥65 years is recommended given the higher rate of amyloid positivity in this age group. 1
Recommended Screening Tests Beyond Basic Labs
Cognitive Testing (Primary Screening Tool)
Administer the Montreal Cognitive Assessment (MoCA) or Mini-Mental State Examination (MMSE) as the primary screening tool. 2 The MMSE with a cut point of 23/24 or 24/25 is appropriate for most primary care populations, though sensitivity and specificity vary by age and education level. 1
- Use validated informant-based tools such as the AD8, Alzheimer's Questionnaire (AQ), or IQCODE to assess changes in cognition, function, and behavior from a reliable informant. 2
- Cognitive screening should be performed when signs or symptoms emerge, not as universal screening in asymptomatic individuals. 1
Laboratory Testing
Complete the following basic laboratory workup to exclude reversible causes: 2
- Complete metabolic panel (electrolytes, glucose, calcium, renal and liver function)
- Thyroid function (TSH, free T4) as hypothyroidism commonly mimics dementia
- Vitamin B12, folate, and homocysteine levels
- Lipid panel and A1C (as you mentioned already performing)
When NOT to Order CT Head or MRI
Routine structural neuroimaging (CT or MRI) is not indicated for asymptomatic screening, even with a positive family history. 1, 3
Neuroimaging should only be obtained when: 1, 2
- Cognitive impairment has been documented on formal testing
- Atypical features are present (e.g., early-onset symptoms, rapid progression, focal neurological signs)
- There is need to exclude other pathology (stroke, tumor, normal pressure hydrocephalus)
- Results will change management decisions
Advanced Biomarker Testing (When Cognitive Decline is Detected)
If cognitive screening reveals impairment, consider advanced testing: 1, 2
Amyloid PET/CT Indications
Amyloid PET/CT is appropriate when: 1
- Patient is <65 years with suspected AD
- MCI or dementia has atypical features
- Prognostic information is needed
- Results will change management decisions
- CSF biomarkers are equivocal or inconclusive
MRI Brain (Not CT)
If neuroimaging is indicated after cognitive impairment is detected, MRI brain without contrast is preferred over CT head. 1 MRI provides superior assessment of:
- Hippocampal atrophy
- Temporal lobe changes
- White matter disease
- Vascular contributions to cognitive impairment
CSF Biomarkers
Consider lumbar puncture for Aβ42, total tau, and phosphorylated tau when diagnosis remains uncertain after initial workup. 2
Monitoring Schedule for At-Risk Individuals
If initial cognitive screening is normal, repeat cognitive assessment annually starting at age 65, or every 6-12 months if mild cognitive impairment is detected. 2
- Heightened surveillance should continue even if initial screening is negative, as risk can change over time. 1
- Annual assessments should include cognitive testing, functional status evaluation, and screening for depression/anxiety. 2
Critical Pitfalls to Avoid
Do not order "routine" CT head scans for asymptomatic patients with family history alone. 1 This represents low-value care and exposes patients to unnecessary radiation and potential false-positive findings leading to further unnecessary testing.
Do not rely solely on patient self-report of memory concerns. 2 Approximately 40-50% of older adults report subjective memory symptoms, but corroborative history from an informant using structured tools is essential for accurate assessment. 1
Recognize that the U.S. Preventive Services Task Force concludes that evidence for universal cognitive screening in asymptomatic older adults is insufficient (I statement). 1, 3 However, clinicians should remain alert to early signs or symptoms and evaluate appropriately when concerns arise.