What is the role of a PET (Positron Emission Tomography) scan in diagnosing dementia in a geriatric patient?

PET Scan in Dementia Diagnosis

For patients with cognitive impairment undergoing dementia evaluation, obtain FDG-PET when the underlying pathological process remains unclear after baseline clinical assessment and structural brain imaging (MRI or CT), as it provides superior diagnostic accuracy for differentiating dementia subtypes compared to clinical evaluation alone. 1

Algorithmic Approach to PET Imaging in Dementia

Step 1: Initial Structural Imaging

• Begin with MRI brain without contrast (or CT if MRI contraindicated) to exclude structural mimics like subdural hematomas, mass lesions, and to assess atrophy patterns 1
• Use semi-quantitative scales including medial temporal lobe atrophy (MTA) scale, Fazekas scale for white matter changes, and global cortical atrophy (GCA) scale 1

Step 2: When to Order FDG-PET

Order FDG-PET in the following scenarios:

• Diagnostic uncertainty persists after structural imaging and specialist evaluation, preventing adequate clinical management 1
• Atypical clinical presentations including nonamnestic presentations, rapid or slow disease progression, or etiologically mixed presentations 1
• Early-onset dementia (age <65 years) where typical atrophy patterns may be absent 1
• Need to differentiate between Alzheimer's disease and frontotemporal dementia, as FDG-PET demonstrates disease-specific metabolic patterns with 89.6% diagnostic accuracy 2, 3
• Documented cognitive decline of at least 6 months with recently established dementia diagnosis 4

FDG-PET demonstrates specific patterns:

• Alzheimer's disease: hypometabolism in parietal and temporal lobes, precuneus, and posterior cingulate gyrus (sensitivity 75-99%, specificity 71-93%) 2, 5
• Frontotemporal dementia: hypometabolism in prefrontal, frontal, and anterior temporal regions (sensitivity 60%, positive predictive value 78.5%) 4, 3
• Dementia with Lewy bodies: decreased occipital glucose metabolism 3

Step 3: When to Order Amyloid PET

Amyloid PET should be ordered by dementia specialists only and is appropriate for: 1

• Persistent or progressive unexplained mild cognitive impairment 1, 2
• Possible Alzheimer's disease with unclear clinical presentation or atypical course 1, 2
• Progressive dementia with early age of onset 1, 2
• Required before initiating antiamyloid monoclonal antibody therapy 1, 2
• When FDG-PET results remain inconclusive in suspected Alzheimer's disease 1

Cost considerations dictate obtaining FDG-PET before proceeding to amyloid imaging. 1

Step 4: Interpreting Amyloid PET Results

Negative amyloid PET:

• Indicates sparse to no neuritic plaques, inconsistent with neuropathological Alzheimer's disease diagnosis 6
• Reduces likelihood that cognitive impairment is due to Alzheimer's disease 6
• Reliably points toward non-Alzheimer's disease dementia such as frontotemporal dementia 7
• Does not completely rule out Alzheimer's disease, especially with strong clinical symptoms 7

Positive amyloid PET:

• Indicates moderate to frequent amyloid neuritic plaques present in Alzheimer's disease 6
• Does not establish a diagnosis of Alzheimer's disease or other cognitive disorder 6
• May occur in other neurologic conditions and older people with normal cognition 6
• Can predict cognitive and functional decline in atypical Alzheimer's disease presentations 1

Step 5: Combined PET Modalities

When FDG-PET and amyloid PET are used together, they achieve 97% sensitivity and 98% specificity for Alzheimer's disease pathology. 1, 4

• When amyloid and FDG-PET results are incongruent, consider mixed dementia 1, 7
• Integrated PET/MRI systems represent the optimal approach, combining structural and functional imaging 4

Step 6: Alternative When PET Unavailable

• If FDG-PET cannot be practically obtained, perform SPECT regional cerebral blood flow (rCBF) study for differential diagnosis, though it has inferior sensitivity (65-85% for Alzheimer's disease) compared to FDG-PET 1, 5
• DaTscan (¹²³I-Ioflupane SPECT) can establish diagnosis of cognitive impairment linked to Lewy Body Disease when diagnosis remains unconfirmed after specialist evaluation 1
• Obtain FDG-PET before proceeding to DaTscan due to cost considerations 1

Critical Pitfalls and Caveats

Avoid FDG-PET in these situations:

• Severe stage dementia with global impairments shows diffuse hypometabolism regardless of underlying cause and provides no diagnostic value 4
• Hypometabolism has limited specificity in neuropsychiatric cohorts, with up to 40% of primary psychiatric disorder patients showing abnormal findings 4

Important limitations:

• A normal FDG-PET supports exclusion of neurodegenerative etiologies but does not completely exclude frontotemporal dementia, particularly in definite genetic cases 4
• Positive amyloid scans can occur in cognitively normal subjects who do not develop Alzheimer's disease and may occur in non-Alzheimer's disease dementias 2
• Amyloid PET has not been established for predicting development of dementia or monitoring responses to therapies 6
• Interpretation requires consideration of pretest probability, age, clinical presentation, and possibility of multiple pathologies 4

Clinical impact data:

• Amyloid PET changed medical management in 67.8% of MCI patients and 65.9% of dementia patients in the IDEAS study 2
• In early-onset or atypical Alzheimer's disease presentations, amyloid PET led to diagnosis change in 67%, improved diagnostic confidence in 81.5%, and altered patient management in 80% of cases 1