Joint Program in Nuclear Medicine

Autosomal Dominant Alzheimer's Disease

John P. Kalabat, MD
Alan J. Fischman, MD PhD

September 30, 2003

Presentation

A 34-year-old woman presented with confusion.

Imaging Findings

Fluorodeoxyglucose positron emission tomographic (FDG-PET) coronal (A), sagittal (B), and axial (C) images show diffuse hypometabolism of the bilateral frontal, parietal, and temporal lobes with relative sparing of the primary sensorimotor cortex (shown with long arrows), primary visual cortex (shown by arrows), and subcortical structures (shown with arrowheads) of the brain.

Diagnosis

Autosomal Dominant Alzheimer’s Disease

Discussion

The majority of cases of Alzheimer’s disease occur sporadically. Less than 10% of cases are familial.

On pathology, senile plaques and neurofibrillary tangles are seen. Unfortunately, diagnosis this way can only be done after death or by biopsy.

On clinical examination, progressive, chronic deficits in middle aged and older patients are often seen. Deficits include memory loss, language disorders, and impaired visuospatial skills.

Alzheimer’s Disease Imaging Findings by FDG-PET

There is decreased whole brain metabolism progressing from the posterior parietal and temporal cortex to frontal lobes.
Parietal and temporal lobes tend to be more severely involved over time.
Early findings include temporal and parietal hypometabolism, which is frequently asymmetric.
Later, involvement may be more symmetric with frontal involvement.
Very late in the disease, one may find generalized hypometabolism, with relative sparing certain areas, including the primary sensorimotor cortex, primary visual cortex, and subcortical structures of the brain.

Differential diagnosis by PET includes bilateral parietal subdural hematomas and bilateral parietal radiation ports.

Variations in pattern on PET can occur in some patients with advanced age, and in patients with severe visuospatial disturbances. In some patients with advanced age, biparietal and bitemporal hypometabolism can be less severe. In patients with severe visuospatial disturbance, parietal and occipital hypometabolism occurs including the primary visual cortex.

Anatomic Imaging Studies

Anatomical studies for Alzheimer’s disease include MRI and CT. These are generally considered part of routine workup. They usually reveal nonspecific atrophy. Medial temporal lobe atrophy is suggestive in proper clinical setting. Anatomic studies are most helpful in ruling out other causes of dementia.

Functional Imaging and Alzheimer’s disease

Single photon emission computed tomography (SPECT) perfusion studies can be performed with ECD and HMPAO. Perfusion abnormalities usually parallel PET findings. When comparing PET and SPECT, it is easier to separate a normal healthy volunteer from Alzheimer is patient with PET. There is generally good concordance between perfusion and glucose metabolism in the temporoparietal and posterior cingulate areas. More variable concordance can be seen in the frontal cortex and the cerebellum.

Dynamic susceptibility-contrast MR perfusion imaging is done with Rapid T2*-weighted imaging of the brain during intravenous injection of a bolus of paramagnetic contrast material. MR perfusion measurements of cerebral blood volume closely parallel changes in FDG. MR perfusion may be a lower cost alternative to PET.

Thereapy

The mainstay of Alzheimer’s disease therapy includes acetylcholinesterase inhibitors. They are indicated for only mild to moderate cases. Accurate diagnosis of early Alzheimer’s is needed if patients are to benefit.

Utility of PET

The literature suggests it is not cost effective to add functional imaging to the standard diagnostic work-up for Alzheimer’s disease. The reasoning is that therapy safe and may be given to people with a general diagnosis of dementia empirically. However, reversible causes of dementia may be less likely to be diagnosed with this line of reasoning (such as depression), and these patients may not receive appropriate treatment.

A potential role of PET is to follow a patient during therapy to determine the effectiveness of therapy. Improved cerebral glucose metabolism has been demonstrated after therapy with cholinesterase inhibitors.

References

Kumar A, Schapiro MB, Grady C, et al. High-resolution PET studies in Alzheimer’s disease. Neuropsychopharmacology 1991;4:35-46

Jagust WJ, Friedland RP, Budinger TF, Koss E, Ober B. Progression of regional cerebral metabolic abnormalities in Alzheimer’s disease. Neurology 1988;38:909-12

Pamela M. McMahon, Sally S. Araki, Eileen A. Sandberg, Peter J. Neumann, and G. Scott Gazelle. Cost-Effectiveness of PET in the Diagnosis of Alzheimer Disease Radiology 2003 228: 515-522

Gonzalez RG, Fischman AJ, Guimaraes AR, et al. Functional MR in the evaluation of dementia: correlation of abnormal dynamic cerebral blood volume measurements with changes in cerebral metabolism on positron emission tomography with fludeoxyglucose F18. AJNR Am J Neuroradiol 1995; 16:1763-1770

Smith GS, de Leon MJ, George AE, et al. Topography of cross sectional and longitudinal glucose metabolic deficits in Alzheimer is disease. Pathophysiologic implications. Arch Neurol 1992;49:1142-50

Jeffrey R. Petrella, R. Edward Coleman, and P. Murali Doraiswamy Neuroimaging and Early Diagnosis of Alzheimer Disease: A Look to the Future Radiology 2003; 226: 315-336.

Karl Herholz, Helge Schopphoff, Mathias Schmidt, R¸diger Mielke, Wolfgang Eschner, Klemens Scheidhauer, Harald Schicha, Wolf-Dieter Heiss, and Klaus Ebmeier. Direct Comparison of Spatially Normalized PET and SPECT Scans in Alzheimer’s Disease. J. Nucl. Med. 2002 43: 21-26.

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J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu