Olfactory impairment in posterior cortical atrophy

INTRODUCTION Olfactory dysfunction develops in many neurodegenerative diseases, and is an early feature of the most common neurodegen-erative disorder, Alzheimer's disease (AD). 1–5 Anatomically, the central olfactory pathways traverse brain regions implicated in the common neurodegenerative diseases, including the mesial temporal and inferior frontal lobes. 6–10 Phenotypically, AD shows substantial diversity with several important variant syndromes, notably posterior cor-tical atrophy (PCA), 11 which is underpinned by AD pathology in over 70% of cases across series. Olfactory impairment in PCA might act as an early signal of underlying AD pathology in these clinically atyp-ical cases; while if olfactory processing were spared in PCA, this would imply that olfac-tion depends chiefly on disease topography. However, there is presently very little information concerning olfaction in PCA. Here we compared olfactory function prospectively in cohorts of patents with PCA and typical AD (tAD). Neuroanatomical associations of odour identification were assessed using voxel-based morphometry (VBM). We hypothe-sised that PCA would be associated with olfactory impairment qualitatively similar to tAD, but less severe (reflecting differential involvement of olfactory cortex); and that deficits of odour identification in both syndromes correlate with grey matter loss in anteromedial temporal and inferior frontal lobes. 2 6–10 METHODS Fifteen patients fulfilling consensus criteria for PCA, 11 10 patients fulfilling The National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for tAD and 32 healthy control (HC) subjects participated. Cerebrospinal fluid (CSF) measurements, available for four patients with PCA, revealed a raised total-τ:β-amyloid ratio (>1) in each case, consistent with underlying AD. Informed consent was obtained from all subjects and the study had local ethics committee approval. All subjects had a comprehensive general neuropsychological assessment which corroborated the clinical impression in both disease groups (see online supplementary table S1). Further details about the behavioural assessments are in online supplementary material. Olfactory processing was assessed using the 40-item, four-alternative-forced-choice University of Pennsylvania Smell Identification Test (UPSIT: British version). 12 We modified the standard UPSIT in two ways: on each trial, the subject was asked to categorise the source of the odour as edible or inedible (see online supplementary table S2) before identifying it; and target-foil choices were name-picture combinations rather than odour names alone, to maximise available response cues. Group differences were assessed using analysis of variance (ANOVA) or χ 2 tests (Stata V.12.1), adjusting for cognitive severity, verbal processing measures , age …