Olfactory impairment in frontotemporal dementia: A systematic review and meta-analysis

Frontotemporal dementia (FTD) presents clinically in three variants: one behavioral and two with progressive primary aphasia - non-fluent/agrammatic and semantic. Defined by the degenerative process and cerebral atrophy, olfactory dysfunction occurs in up to 96% of previous FTD case series. OBJECTIVE: the present study aims to critically synthesize data about the relationship between FTD and olfactory impairment to analyze the usefulness of olfactory evaluation tests as a complementary element in early diagnosis. METHODS: a database search was performed using the keywords “olfactory OR smell OR olfaction AND frontotemporal dementia”. We included studies that evaluated olfactory function in patients diagnosed with frontotemporal dementia, all subtypes, compared with age-matched healthy controls. For comparative purposes, the effect size was calculated using Cohen’s D. The studies selected were categorized according to dementia variant and olfactory test type. A meta-analysis was performed using forest plots - homogeneity was evaluated by statistical tests (i(2) and Cochran Q). RESULTS: ten articles met the inclusion criteria. Heterogeneity was classified as low for semantic dementia olfactory identification and behavioral variant olfactory discrimination groups (i(2) = 0 and 3.4%, respectively) and as moderate for the behavioral variant olfactory identification group (i(2) = 32.6%). CONCLUSION: patients with the frontotemporal dementia behavioral variant seem to present with alterations in odor identification, but with preserved discrimination. Scent identification also seems to be impaired in semantic dementia. Therefore, we conclude that olfactory evaluation in these patients is possibly impacted by cognitive alterations and not by sensory deficits. Application of olfactory tests may prove important in differentiating prodromal states from other types of dementia with more pronounced olfactory impairment.