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

Abstract

ABSTRACT. 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 (i2 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 (i2 = 0 and 3.4%, respectively) and as moderate for the behavioral variant olfactory identification group (i2 = 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.

Chronic neuropsychiatric sequelae of SARS‐CoV‐2: Protocol and methods from the Alzheimer's Association Global Consortium

“…Neuroimaging in sub‐acute COVID‐19 patients also provided evidence of regional involvement of the olfactory bulb and its first‐ and second‐order projections 29–34 . We note too that involvement of the olfactory cortical network in early Alzheimer's disease (AD) is well established, and olfactory dysfunction is a strong clinical correlate of mild cognitive impairment (MCI) in AD and other forms of dementia 35–37 …”

“…166,167 Olfactory impairment is also correlated with tau pathology and neuroinflammation in patients with ADRD 168 and predictive of dementia diagnosis in several pathologies. 36,37 As mentioned in the introduction, SARS-CoV-2 invades the olfactory bulb, and this is the likely explanation for the prevalent anosmia in infected patients. [20][21][22][24][25][26][27] This mechanism has been well established in experimental animals 26 and is well supported by imaging studies of sub-acute COVID-19 patients.…”

“…[29][30][31][32][33][34] We note too that involvement of the olfactory cortical network in early Alzheimer's disease (AD) is well established, and olfactory dysfunction is a strong clinical correlate of mild cognitive impairment (MCI) in AD and other forms of dementia. [35][36][37] Other possible (or additive) pathological mechanisms that may underlie chronic neurological consequences of SARS-CoV-2 infection include persistent cytokine-mediated inflammation, antibodymediated autoimmunity, and cerebrovascular pathology. These all contribute to the acute neurological complications of COVID-19 and may act as predisposing factors or ongoing insults for chronic or progressive neurological impairment.…”

International consensus statement on allergy and rhinology: Olfaction

“…The olfactory sensory neural pathway includes numerous brain regions implicated in the pathophysiology of a number of developmentally mediated neuropsychiatric disorders 919–944 . Notably, in the past two decades, the literature concerning psychophysical OF and its associated structural brain, physiological, and clinical correlates has exponentially grown, providing crucial insights into the developmental and clinical aspects of these neuropsychiatric disorders.…”

Development of the Spanish Version of Sniffin’s Sticks Olfactory Identification Test: Normative Data and Validity of Parallel Measures

“…Olfactory tests are necessary tools for adequate assessment of olfactory function [ 1 ]. The use of olfactory assessment tests has become more relevant in recent years, due to clinical and research findings that indicate the existence of olfactory alterations derived from traumatic injuries as brain injury [ 2 , 3 ], in surgical or medical procedures for the treatment of some diseases such as larynx tumors requiring partial or total laryngectomy [ 4 ], treatment with radiotherapy [ 5 ], or pathologies with alterations of the sense of smell such as arterial hypertension [ 6 ], liver disease [ 7 , 8 ], diabetes mellitus [ 9 , 10 ], rhinitis, sinusitis [ 11 , 12 ], autoimmune diseases [ 13 , 14 ], inflammatory diseases [ 15 ], anxiety [ 16 , 17 ], major depression [ 18 , 19 , 20 , 21 ], schizophrenia [ 22 ], autism [ 23 ], and neurodegenerative diseases [ 24 , 25 ], such as frontotemporal dementia [ 26 , 27 , 28 ], amyotrophic lateral sclerosis [ 29 ], Parkinson’s disease [ 30 , 31 , 32 , 33 ], or Alzheimer’s disease [ 33 , 34 , 35 , 36 ].…”