On the right side? A longitudinal study of left- versus right-lateralized semantic dementia

Abstract

The typical presentation of semantic dementia is associated with marked, left predominant anterior temporal lobe atrophy and with changes in language. About 30% of individuals, however, present with predominant right anterior temporal lobe atrophy, usually accompanied by behavioural changes and prosopagnosia. Here, we aimed to establish whether these initially distinct clinical presentations evolve into a similar syndrome at the neural and behavioural level. Thirty-one patients who presented with predominant anterior temporal lobe atrophy were included. Based on imaging, patients were categorized as either predominant left (n = 22) or right (n = 9) semantic dementia. Thirty-three Alzheimer's disease patients and 25 healthy controls were included for comparison. Participants completed the Addenbrooke's Cognitive Examination, a Face and Emotion Processing Battery and the Cambridge Behavioural Inventory, and underwent magnetic resonance imaging annually. Longitudinal neuroimaging analyses showed greater right temporal pole atrophy in left semantic dementia than Alzheimer's disease, whereas right semantic dementia showed greater orbitofrontal and left temporal lobe atrophy than Alzheimer's disease. Importantly, direct comparisons between semantic dementia groups revealed that over time, left semantic dementia showed progressive thinning in the right temporal pole, whereas right semantic dementia showed thinning in the orbitofrontal cortex and anterior cingulate. Behaviourally, longitudinal analyses revealed that general cognition declined in all patients. In contrast, patients with left and right semantic dementia showed greater emotion recognition decline than Alzheimer's disease. In addition, left semantic dementia showed greater motivation loss than Alzheimer's disease. Correlational analyses revealed that emotion recognition was associated with right temporal pole, right medial orbitofrontal and right fusiform integrity, while changes in motivation were associated with right temporal pole cortical thinning. While left and right semantic dementia show distinct profiles at presentation, both phenotypes develop deficits in emotion recognition and behaviour. These findings highlight the pervasive socio-emotional deficits in frontotemporal dementia, even in patients with an initial language presentation. These changes reflect right anterior temporal and orbitofrontal cortex degeneration, underscoring the role of these regions in social cognition and behaviour.

Reading words and other people: A comparison of exception word, familiar face and affect processing in the left and right temporal variants of primary progressive aphasia

“…This may relate to early misdiagnosis of right temporal cases (see Discussion). We also observed evidence of asymmetric spread of atrophy to posterior temporal regions (Brambati, Rankin, et al, 2009; Kumfor et al, 2016; Rohrer et al, 2009). The L-svPPA group, on average, exhibited 22.3% volume loss in the left cTL (range = 0–36%) and 4.3% in the right cTL (0–16%).…”

“…At initial clinical presentation, atrophy is typically bilateral though usually asymmetric with more extensive left hemisphere involvement. Over time, atrophy spreads through the initially less affected contralateral rostral temporal cortex and also to ipsilateral ventromedial frontal, insular and infero-posterior temporal regions (Brambati, Rankin, et al, 2009; Kumfor et al, 2016; Rogalski et al, 2014). Less frequently (approximately 30% of cases), patients present with greater right than left rostral temporal involvement.…”

The Relationship between Behavioural Changes, Cognitive Symptoms, and Functional Disability in Primary Progressive Aphasia: A Longitudinal Study

“…For patients in the earlier stages of disease, this may have impacted on their clinical presentation, with right-sided patients exhibiting worse behavioural symptoms than patients with predominantly left-sided temporal lobe atrophy. With progression, however, the clinical profile of these subtypes becomes similar as left-sided svPPA also exhibit behavioural symptoms [25,26]. Paradoxically, semantic deficits appear not to be a main contributing factor to functional decline, given that they appear very early in the disease and at a time when ADL function is very well preserved.…”

Primary progressive aphasia: conceptual evolution and challenges

“…Evidence from a longitudinal cohort, however, demonstrates that those cases develop marked language deficits, demonstrating that irrespective of the initial clinical presentation, all sv-PPA cases evolve into a similar syndrome at the neural and behavioral level. 45 This convergent clinical progression shows not only the common nosology in both sv-PPA presentations, but it also suggests the relevance of observing the clinical trajectory to refining diagnosis. Of clinical importance, unlike other variants, almost all cases with sv-PPA develop some degree of behavioral symptoms such as agitation and delusions that can become disruptive and require pharmacological intervention.…”

“…43,44 Longitudinal studies in the other variants, in contrast, have demonstrated that sv-PPA presents the slowest rate of progression and semantic disintegration remains the most salient deficit and declines in a fairly stereotyped manner. 41,45,46 Similarly, expressive language deficits in nfv-PPA remains the most salient clinical problem, and before other linguistic deficits become prominent, extrapyramidal deficits often emerge. 47,48 The widespread and heterogeneous clinical involvement in lv-PPA has been the main motivation to suggest that this variant should be excluded from the spectrum of PPA presentations.…”