ALZHEIMER’S DISEASE IMAGING
Wessam Bou-Assaly, MD
Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by the gradual onset of demetia. The pathologic hallmarks of the disease are beta-amyloid plaques, neurofibrillary tangles (NFTs), and reactive gliosis.
Alzheimer disease was first described in 1907 by Alois Alzheimer and has become one of the most common diseases in the aging population, ranking as the fourth most common cause of death.
It is the most common cause of dementia, responsible for 60-80% of all dementias.
The prevalence is strongly linked to age, with >1% of 60-64 year old patients being diagnosed with the condition, compared to 20-40% of those over 85-90 years of age.
Epidemiological risk factors include:
-Advanced age
-Female gender
- Apolipoprotein E (APOE) ε4 allele carrier status
-Current smoking
-Family history of dementia
-Mutations of amyloid precursor protein
DIAGNOSIS:
Clinical diagnosis is made by identifying progressive decline in memory both with clinical examinations and neuropsychologic tests and has been historically based on the the INCDS-ADRA criteria, which divides patients according to the certainty of the diagnosis into 5:
1. Definite: clinical diagnosis and histologic confirmation.
2. Probable: typical clinical syndrome without histologic confirmation 81% sensitive, 73% specific.
3. Possible: atypical clinical features without histologic confirmation.
IMAGING:
CT SCAN:
The initial criteria for CT scan diagnosis of Alzheimer disease includes diffuse cerebral atrophy with enlargement of the cortical sulci and increased size of the ventricles.
Disproportionate atrophy of the medial temporal lobe, particularly of the volume of the hippocampal formations (< 50%), is highly suggestive of AD.
Dilatation of the perihippocampal fissure is a useful radiologic marker for the initial diagnosis of Alzheimer disease, with a predictive accuracy of 91%. The hippocampal fissure is surrounded laterally by the hippocampus, superiorly by the dentate gyrus, and inferiorly by the subiculum. These structures are all involved in the early development of Alzheimer disease and explain the enlargement in the early stages.
MRI:
Magnetic resonance imaging (MRI) is considered the neuroimaging of choice for Alzheimer disease because it allows for accurate measurement of the 3-dimensional (3D) volume of brain structures, especially the size of the hippocampus and related regions.
MRI is also useful for excluding reversible causes of dementia syndrome, such as normal pressure pressure hydrocephalus, brain tumors, and subdural hematoma, and for excluding other likely causes of dementia, such as cerebrovascular disease.
The primary role of MRI in the diagnosis of Alzheimer disease is the assessment of volume change in characteristic locations which can yield a diagnostic accuracy of up to 87% .
The diagnosis should be made on the basis of two features:
1. Mesial temporal lobe atrophy.
2. Temporoparietal cortical atrophy.
Mesial temporal lobe atrophy can be viewed directly by assessing for hippocampal and parahippocampal decrease in volume, or indirectly by examining enlargement of the parahippocampal fissures.
The former is more sensitive and specific but ideally requires actual volumetric
calculations rather than simple visual assessment. These measures have been combined in
the “medial temporal atrophy score ” which has been shown to be predictive of
progression from mild cognitive impairment (MCI) to dementia.
Particularly relevant to early onset Alzheimer disease, is the presence of temporoparietal and parietal atrophy. This is often best seen on the interhemispheric surface of the parietal lobe by examining the posterior cingulate sulcal and
parietoccipital sulcal size and degree of atrophy of the precuneus and cortical surface of the parietal lobe. This has also been combined into a scoring system.
18-FDG Positron Emission Tomography (PET)
F-18 FDG PET typically shows bilateral temporoparietal, precuneus and posterior cingulate hypometabolism which is usually symmetric. Uptake may be asymmetric in the early stages.
Amyloid PET
Pittsburgh Compound B, along with newer compounds such as florbetapir, flutametamol, and florbetaben, are molecules that bind preferentially to beta-amyloid fibrils is being used with PET and may be able to improve the specificity of AD diagnosis, although there is considerable overlap with normal controls.
With increased cerebral amyloid-β (Aβ) deposition, increased activity is demonstrated in the cortex. It is particularly useful in excluding Alzheimer's disease as the cause of dementia, since a negative amyloid PET scan makes the diagnosis unlikely.
Wessam Bou-Assaly, MD is a Radiologist specialized in Neuroradiology and Head and Neck Imaging.
