The featured article is ‘Anosmia is very common in the Lewy Body Variant of Alzheimer’s Disease’ by Olichney and colleagues and freely available here. In the introduction, the authors note the difficulties that sometimes occur in distinguishing between Lewy Body Dementia and Alzheimer’s Disease and this is complicated by cases in which there is marked overlap between the two which they refer to as the ‘Lewy Body Variant of Alzheimer’s Disease’. The authors identify two clear aims in their study
1. To confirm earlier findings by McShane and colleagues who found increased anosmia in Lewy Body Dementia but not Alzheimer’s Disease
2. To see if the smell test can facilitate discrimination of Alzheimer’s Disease from Lewy Body Dementia (DLB)
The sample population consisted of people who had been assessed with an odour threshold test at the Alzheimer’s Disease Research Center (ADRC) in California and who had subsequently undergone necropsy between 1988 and 2001. The CERAD neuropathological criteria for probably/possible Alzheimer’s Disease in combination with DSM-III R criteria for dementia were used as well as consensus clinical criteria for DLB. 106 cases were identified (Alzheimer’s Disease 89; 17 Lewy Body Variant). All subjects had given written consent for this longitudinal research program. There had also been annual neurological reviews which included a detailed assessment of Parkinson’s related features. A detailed olfactory test was used with increasing concentrations of n-butyl alcohol being used if the person was unable to discriminate between this and a stimulus with no odour.
The presence or absence of anosmia or Lewy Bodies were the dependent variables and there were a number of independent variables such as severity of dementia and visual hallucinations used in the analysis. A regression model was constructed using backward and forward step regression analyses. Anosmia was present in 64.7% of cases of Lewy Body Dementia and 22.5% of cases of Alzheimer’s Disease and this difference between the group was significant at the 0.00045 level (using a Chi Squared test)!. The odour test attained 65% sensitivity and 78% specificity for LBV. However the test was less useful in smokers because of the relationship between smoking and olfaction (see Appendix 1). Indeed the sensitivity from the consensus diagnosis of DLB had 100% specificity but a low sensitivity. Adding anosmia to the diagnostic criteria had variable effects depending on the population – smokers or non-smokers. For instance in non-smokers, addition of anosmia produced a specificity of 88/89 but a sensitivity of 7/17. Higher education, low severity scores and Lewy Bodies were the three significant independent variables identified from the regression analysis.
In conclusion, the authors of the study found that anosmia is more common in Lewy Body Dementia than in Alzheimer’s Disease although it is also moderately correlated with dementia severity and in the Alzheimer’s Group was associated with a reduced survival period. The paper is well written, being easy to understand and conveying the methodology and results unambiguously. The results are clinically relevant and the authors are cautious in their conclusions while also indicating how they can be used. Subsequently there has been the suggestion that under circumstances in Parkinson’s Disease, biopsy of the Olfactory Bulb could be warranted (Appendix 2).
Steps To Treatment
STT 4 (Replication, Meta-analysis, Incorporation into diagnostic policies if appropriate, then one further step to treatment)
Beach T et al. Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy Body Disorders. Acta Neuropathol. 2009. 117(2). 169-74.
Katotomichelakis M et al. The effect of smoking on the olfactory function. Rhinology. 2007. 45(4). 273-80.
Olichney J et al. Anosmia is very common in the Lewy Body variant of Alzheimer’s Disease. J Neurol Neurosurg Psychiatry. 2005. 76. 1342-1347.
Appendix 1 – Smoking and Olfaction
In a study of 65 smokers – (median smoking period of 10 years0) and 49 non-smokers a significant inverse correlation between pack-years of smoking and odour threshold, odour discrimination and odour identification were found.
Appendix 2 – Olfactory Bulb and Alpha-synucleinopathy
In a study which included 328 post-mortems of people who had known Parkinson’s Disease, there was found to be a significant correlation of Olfactory Bulb Alpha-Synucleinopathy density scores and those in other regions at necropsy including limbic cortex. There was also a significant correlation with MMSE scores antemortem and scores on the Unified Parkinson’s Disease Rating Scale.
Steps To Treatment (STT)
STT = Steps To Treatment. An estimate of the number of steps between the results and translation into practice i.e. treatment. This is an opinion.
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