Advances in Diagnosis

Increasingly, research findings have highlighted pathological differences and potential biomarkers for differential diagnosis between DLB and Alzheimer’s. In a study published in September 2015 in Neurobiology of Aging,7 Dr Peraza and colleagues used resting-state functional magnetic resonance imaging to investigate differences in functional brain networks between 22 DLB patients and 24 Alzheimer’s patients who were cognitively matched. They found that “in Alzheimer’s there are disconnections of the temporal cortices from the rest of brain, while in DLB these disconnections occur in parietal and occipital cortices,” he told Neurology Advisor. “The parietal cortices host neuronal circuitry in charge of our attention and spatial perception mechanisms, hence the related impairments in these regions with DLB.”

Studies involving other imaging modalities have similarly shown key differences between DLB and Alzheimer’s. Using MRI in a cohort of patients in an early disease state (MCI or prodromal),8 researchers “found that Alzheimer’s patients initially have an atrophy in the parietal lobes and hippocampi – this fact was well-known previously — and that DLB patients initially have atrophy in the insula,” said study co-author Frederic Blanc, MD, PhD, a neurologist and geriatrician at the University of Strasbourg. Future research should investigate whether insular atrophy in particular could be useful in DLB diagnosis, he said.


Continue Reading

In a study published in the International Journal of Geriatric Psychiatry in November 2015,9 researchers investigated the “diagnostic performance of brain acetylcholinesterase (AChE) activity measurement using N-[(11) C]-methyl-4-piperidyl acetate (MP4A) and PET in patients” with DLB and Alzheimer’s. Their findings showed a consistent cholinergic deficit in the 14 DLB patients as compared to the 25 Alzheimer’s patients, suggesting that “PET measurement of brain AChE activity may be useful for the differential diagnosis between DLB and Alzheimer’s,” the authors wrote.

Working With What’s Available

While researchers expand their investigations into the diagnostic utility of those techniques, there are currently neuroimaging tests that can facilitate differential diagnosis. “For instance, with structural magnetic resonance imaging (sMRI), an experienced radiographer might assess if there is structural damage in the hippocampi which is indicative of Alzheimer’s,” Dr Peraza said. “Additionally, with dopaminergic imaging it is possible to assess for the presence of Lewy body disease by studying the integrity of the dopaminergic system.”

Other forms of testing that have shown promise in research trials are EEG,10 cardiac scintigraphy,11 analysis of cerebrospinal fluid biomarkers,12 and memory and visual tasks. In a study published in 2015, Dr Salmon and colleagues tested autopsy-confirmed DLB and Alzheimer’s patients on various recognition memory tasks.13 According to results, recognition memory spans were lower in DLB patients than in Alzheimer’s patients, possibly “due to greater fronto-striatal involvement in DLB and a corresponding decrement in cooperative interaction between working memory and secondary memory processes,” the authors wrote. “Assessment of recognition memory span may contribute to the ability to distinguish between DLB and Alzheimer’s relatively early in the course of disease.”

In another recent study, Dr Salmon and colleagues found that “patients with DLB are significantly more impaired than patients with Alzheimer’s on a task that requires discrimination of the direction of motion in complex visual stimuli,” he said.14

Look and Listen

Dr O’Brien advises that clinicians should ask patients with cognitive problems and their caregivers whether the patient is experiencing visual hallucinations, variations in cognition, and sleep disturbance, particularly REM sleep behavior disorder (RBD).

Findings published in the Lancet Neurology in 2013 show that 82% of patients with idiopathic RBD had developed a neurodegenerative disease when they were assessed at a follow-up session years later.15 The authors concluded that idiopathic RBD “represents the prodromal phase of a Lewy body disorder.” Clinicians should also look carefully for motor signs in patients with dementia, added Dr O’Brien.

Along with various tools and diagnostic criteria, clinical training and experience are essential in differentiating between DLB and Alzheimer’s, especially at the early stages when variations may be nearly indiscernible. “An experienced clinician will notice that in an Alzheimer’s patient, fluctuations in cognition are related to memory, such as forgetting things, which is the main characteristic of Alzheimer’s, while in a DLB patient these fluctuations are related to attention deficits, as when the patient might appear distant when having a conversation,” said Dr Peraza. Clinicians should be aware of these nuances and seek DLB-specific training or the opinion of a more experienced colleague if necessary.

References

  1. What is LBD?. Lewy Body Dementia Association Web site. https://www.lbda.org/category/3437/what-is-lbd.htm. Accessed January 25, 2016.
  2. Caregiver Burden in Lewy Body Dementias (white paper). Lewy Body Dementia Association. 2010.
  3. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005; 65(12):1863-72.
  4. Slaets S, Le Bastard N, Theuns J, et al. Amyloid pathology influences aβ1-42 cerebrospinal fluid levels in dementia with lewy bodies. J Alzheimer’s Dis. 2013; 35(1):137-46.
  5. McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet. 2000.356(9247):2031-6.
  6. Emre M, Tsolaki M, Bonuccelli U, et al. Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010 Oct. 9(10):969-977.
  7. Peraza LR, Taylor JP, Kaiser M, et al. Divergent brain functional network alterations in dementia with Lewy bodies and Alzheimer’s disease. Neurobiol Aging. 2015; 36(9):2458-67. 
  8. Blanc F, Colloby SJ, Philippi N, et al. Cortical Thickness in Dementia with Lewy Bodies and Alzheimer’s Disease: A Comparison of Prodromal and Dementia Stages. PLoS One. 2015; 10(6):e0127396. 
  9. Shimada H, Hirano S, Sinotoh H, et al. Dementia with Lewy bodies can be well-differentiated from Alzheimer’s disease by measurement of brain acetylcholinesterase activity-a [11C]MP4A PET study. Int J Geriatr Psychiatry. 2015; 30(11):1105-13. 
  10. Lee H, Brekelmans GJ, Roks G. The EEG as a diagnostic tool in distinguishing between dementia with Lewy bodies and Alzheimer’s disease. Clinl Neurophysiol. 2015; 126(9):1735-9. 
  11. Slaets S, Van Acker F, Versijpt J, et al. Diagnostic value of MIBG cardiac scintigraphy for differential dementia diagnosis. Int J Geriatr Psychiatry. 2015; 30(8):864-9. 
  12. Wennström M, Surova Y, Hall S, et al. The Inflammatory Marker YKL-40 Is Elevated in Cerebrospinal Fluid from Patients with Alzheimer’s but Not Parkinson’s Disease or Dementia with Lewy Bodies. PLoS One. 2015; 10(8):e0135458.
  13. Salmon DP, Heindel WC, Hamilton JM, et al. Recognition memory span in autopsy-confirmed Dementia with Lewy Bodies and Alzheimer’s Disease. Neuropsychologia. 2015; 75:548-55.
  14. Landy KM, Salmon DP, Galasko D, et al. Motion discrimination in dementia with Lewy bodies and Alzheimer disease. Neurology. 2015; 85(16):1376-82.
  15. Iranzo A, Tolosa E, Gelpi E, et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol. 2013; 12(5):443-53.