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Journal of Alzheimer’s Disease 40 (2014) 33–36 DOI 10.3233/JAD-131448 IOS Press

Short Communication

Memory and Orientation in the Logopenic and Nonfluent Subtypes of Primary Progressive Aphasia Emma C. Flanagana , Sicong Tua,b,c , Samrah Ahmedd , John R. Hodgesa,b,c and Michael Hornbergera,b,c,e,∗ a Neuroscience

Research Australia, Sydney, NSW, Australia of Medical Sciences, University of New South Wales, NSW, Australia c Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, NSW, Australia d Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK e Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK b School

Accepted 23 October 2013

Abstract. Memory and orientation were investigated as predictors of underlying Alzheimer’s disease (AD) pathology in patients with logopenic (lv) and non-fluent (na) variants of primary progressive aphasia (PPA). Memory and orientation scores from Addenbrooke’s Cognitive Examination were compared between 26 lv-PPA, 29 na-PPA, 59 AD, and 90 controls using analysis of variance. Forty-five patients underwent Pittsburgh compound B (PiB) positron emission tomography scans. Patients with lv-PPA performed poorer on memory and orientation than na-PPA and did not differ from the AD group. Post-hoc analysis on the PiB-scanned subgroup corroborated these results. Memory and orientation profiles may supplement language assessment in identifying patients with AD pathology. Keywords: Memory, orientation, PiB, PPA, lv-PPA, na-PPA

INTRODUCTION Three variants of primary progressive aphasia (PPA) are recognized in the International consensus criteria: nonfluent/agrammatic PPA (na-PPA), logopenic PPA (lv-PPA), and semantic PPA (SD) [1]. The syndrome of SD is well described and the diagnosis presents little difficulty in the majority of cases [2]. By contrast, the diagnosis of na-PPA and lv-PPA is challenging as ∗ Correspondence to: Dr. Michael Hornberger, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0SZ, UK. Tel.: +44 1223 760694; Fax: +44 1223 760694; E-mail: [email protected].

they share some features while the elicitation of key differentiating linguistic signs requires considerable expertise [1, 3]. The correct diagnosis is important since the majority of lv-PPA patients have underlying Alzheimer’s disease (AD) pathology while na-PPA patients do not. This raises the question of whether lvPPA patients have non-language symptoms similar to AD, which so far has been suspected but not yet systematically investigated. Current diagnostic criteria for PPA require isolated language deficits, with prominent initial memory impairment among the exclusionary criteria [1]. By contrast, patients with typical AD are characterized by early deficit in memory and orientation [4], and determining whether these deficits are also

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present in lv-PPA, and furthermore absent in na-PPA, could lead to improved diagnostic accuracy. Therefore, the current study explores memory and orientation performance in lv-PPA, na-PPA, and AD patients to determine whether performance on these measures could be employed as proxy measures to detect underlying AD pathology in the PPA groups and thus could complement language assessments of these patients. METHODS Consecutive patients who clearly met consensus diagnostic criteria were recruited from the Frontotemporal Dementia Clinic at Neuroscience Research Australia in Sydney. Diagnosis of the aphasic patients (17 lv-PPA, 13 na-PPA) was based on the International Consensus Criteria along with the clinical algorithm previously described [5]. AD patients (n = 59) were diagnosed according to diagnostic consensus criteria [1, 4]. Forty-five patients (17 lv-PPA, 13 na-PPA, 15 AD) underwent a positron emission tomography tracer 11C-Pittsburgh compound B (PiB PET). All included lv-PPA and AD cases showed positive neocortical retention of PiB, while all na-PPA cases were PiB negative. PiB profiles were determined based on positive uptake of amyloid protein consistent with established protocols [5]. Neocortical PiB uptake was based on an average uptake ratios of frontal, super parietal, lateral temporal, lateral occipital, and cingulate regions, and a cut-off ratio of 1.5 was applied to distinguish between ‘positive’ and ‘negative’ PiB profiles, with ‘positive’ profiles having ratios higher than this cut-off. Healthy control subjects (n = 90) were selected from the Frontier volunteer panel and age- and education-matched to the patient groups. All patients were tested on a general cognitive screen test, the Addenbrooke’s cognitive examination revised (ACE-R), which includes memory, orientation, and language subscores. Carers of patients completed a neuropsychiatric screening questionnaire (Cambridge Behavioral Inventory revised, CBI-R). Disease severity was assessed using the Rasch score of the Frontotemporal Dementia Rating Scale (FRS) [6], which ranks dementia severity based on different behavioral changes and impairments in everyday functioning that characterize frontotemporal dementia, of which PPA syndromes are variants, with lower Rasch scores indicating greater disease severity. The study was approved by the South Eastern Sydney and Illawarra Area Health Service and the University of New South Wales human ethics committees. Written informed consent was obtained from the participant or primary caregiver.

Data were analyzed using SPSS20 (IBM, Armonk, NY). Prior to any analysis, variables were plotted and checked for normality of distribution via ShapiroWilk tests. Demographic and neuropsychological data were analyzed across the groups via ANOVA, or with Kruskal-Wallis with pairwise comparisons performed using the Dunn [7] procedure, where assumptions for parametric tests were not met. Logistic regressions were performed using the ENTER method in order to evaluate diagnostic accuracy for memory and emotion scores between PPA groups. RESULTS Demographics, ACE-R, and CBI-R scores for all four groups are presented in Table 1. Comparisons of lv-PPA, na-PPA, AD, and control groups revealed no significant difference for age, gender, education, and disease duration (p’s > 0.05). Disease severity (FRS) in AD was significantly higher than in the other two patient groups (p’s < 0.05). Importantly, lv-PPA and na-PPA did not differ on FRS disease severity (p = 0.99). Comparison of the language subscore of the ACE-R showed an effect of group (χ2 (2) = 110.34, p < 0.001), with post-hoc comparisons revealing all patient groups performed worse than controls (p’s

Memory and orientation in the logopenic and nonfluent subtypes of primary progressive aphasia.

Memory and orientation were investigated as predictors of underlying Alzheimer's disease (AD) pathology in patients with logopenic (lv) and non-fluent...
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