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Functional MRI (fMRI) differentiates DLB from AD

New research reveals promise of another brain imaging technique to differentiate between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD).  Functional magnetic resonance imaging (fMRI) revealed distinct differences between individuals with clinically diagnosed DLB from those with AD.  fMRI is a specialized type of MRI scan that measures changes in blood flow related to brain activity, and has grown in prominence due to its relatively low invasiveness, absence of radiation exposure and its relatively wide availability.  fMRI also offers the advantage of being collected during the same session as the structural MRI scan, which is commonly used when diagnosing dementia.  At the present time, fMRI is a research tool only.

Neurons are cells in the brain which process and transmit information by electrical and chemical signaling and require increased levels of glucose and oxygen when activated.  Because neurons do not have internal reserves of glucose and oxygen, this must be delivered through hemoglobin in red blood cells.  Resting state blood-oxygen-level dependence (BOLD) fMRI measures the change in oxygen levels in hemoglobin that is delivered to neurons.  In many studies, this is expressed as “connectivity”, that is how strong the relationship is between two brain regions.

Primary investigator, Dr. James Galvin of New York University, and colleagues studied 88 participants enrolled in a longitudinal study of memory and aging, including 15 with DLB, 35 with AD, and 38 healthy controls.  In addition to fMRI scans, nearly all participants were underwent PET scans with Pittsburgh compound B (PiB), which reveals amyloid deposits (a neuropathological hallmark of Alzheimer’s disease).  All healthy controls had negative PET results, ensuring no pre-clinical Alzheimer’s disease was present, and all AD controls had a positive PET result.  6 out of 13 DLB controls who underwent PET also had positive results, indicating the presence of some Alzheimer’s pathology.

Dr. Galvin and colleagues studied parts of the brain contained within the Default Mode Network (DMN). The DMN is a collection of brain regions that are most active at rest and decrease in activity once the brain begins to perform a task.  The DMN is important for self-evaluation, remembering the past and planning the future.  Once a task begins that requires focused attention, the activity of the DMN decreases dramatically. The DMN has previously been studies as a region of vulnerability in AD, but to date no one has looked at this region in DLB.

Because there are no reliable biomarkers available to diagnose DLB, participants with DLB were recruited from a specialty dementia practice and met published DLB criteria.

  • DLB participants had at least a 2 year gap between the initial onset of dementia and development of motor symptoms, in order to eliminate PD dementia as the clinical diagnosis.
  • The DLB group contained more men than the Control or AD group, thus the investigators had to take into account (also known as “controlling for”) any effects due to gender
  • In the DLB group, 100% had extrapyramidal symptoms, 80% had cognitive fluctuations using the Mayo Clinic Fluctuation questionnaire, 20% had recurrent visual hallucinations using the Neuropsychiatric Inventory, and 47% had features suggestive of REM sleep behavior disorder using the Mayo Clinic Sleep Questionnaire.
  • Six DLB patients were taking dopaminergic agents and all were taking cholinesterase inhibitors.  All the AD patients were taking cholinesterase inhibitors.
  • Patients with AD did not exhibit any core DLB features (fluctuating cognition, visual hallucinations or parkinsonism).

Results:

  • The major findings were that the DLB group had significant differences in the connectivity of the DMN compared with controls and AD. The DLB cases had reversal of connectivity patterns typically seen in controls and AD. Most notably, the DLB cases had increased connectivity between the DMN (resting brain) and dorsal attention networks (active brain).  While the significance of these differences is not yet fully understood, it would suggest that individuals with DLB may “slip” between alert and resting states leading to increased daytime sleepiness, incoherent or illogical thoughts, alterations in attention, alertness and concentration and staring spells.  Dr Galvin’s group is now exploring this possibility in a follow-up study.  
  • One of the limitations of the present study is the small sample size.  It would be interesting to test whether DLB cases with AD pathology are different from those individuals without AD pathology; however the number of cases was not sufficiently large to address this question.

This research suggests distinct patterns of activity that may assist in differentiating DLB from AD, and understanding how changes in brain connectivity may explain individual symptoms associated with disease.  However further research with larger numbers of DLB cohorts will be necessary before BOLD fMRI could be used as a diagnostic test.

The results were published online by Neurology, the journal of the American Academy of Neurology, before print April 27, 2011