Progressive aphasia in Chinese speakers: clinical and neuroradiological findings

Abstract

Objective: Identifying the specific cause of dementia is increasingly important as effective, disease-specific treatments become available. For example, clinicians need a method to accurately differentiate frontotemporal dementia (FTD) from dementia of the Alzheimer's type (DAT). The first symptom of DAT is typically memory loss, while the hallmarks of FTD are behaviour and language disturbance. However, both disorders cause an insidious, gradually progressive de-mentia that lacks distinctive physical signs, and patients with FTD frequently meet diagnostic criteria for AD. It is not surprising therefore that FTD is frequently misdiagnosed. Neuroimaging studies show characteristic differences of grey matter abnormalities in FTD and DAT. In FTD, MRI studies report regional patterns of grey matter atrophy in primarily frontal lobe regions (see Figure 1), similar to the regional patterns of functional changes measured by reduced cerebral blood flow and glucose metabolism from SPECT and PET studies. By comparison, brain atrophy in DAT is initially observed in medial temporal lobe regions, whereas functional changes are more prominent in the parietal lobe (including posterior cingulate gyrus and lateral parietotemporal areas). The frontal lobe regions are generally spared in DAT until late stages. New MRI findings have also shown a different regional distribution of white matter loss in DAT and fMRI. One means of distinguishing FTD and DAT is via assessment of aphasia. Primary progressive aphasia (PPA) is a language disorder characterised by a gradual and isolated deterioration of language function. All patients with PPA display word retrieval impairments (anomia) in the early stages of the illness. However, there are at least two distinct variants of PPA labelled fluent and non-fluent. In the fluent variety, speech production is largely preserved whereas comprehension and semantic memory are impaired. In non-fluent aphasia (NFA), speech is characterised by agrammatic output with speech comprehension, with semantic memory and also episodic memory intact. Progressive aphasia has been reported in several languages including English, French, German, Italian, Japanese, Portuguese, Spanish and Turkish. The pattern of language deterioration in fluent and non-fluent cases is remarkably similar across different languages despite differences in grammatical features. Here we report a study of Chinese speaking patients with dementia investigating the hypothesis that progressive aphasia distinguishes between FTD and DAT. Methods. Patients were recruited from Queen Mary Hospital, Hong Kong and classified using a Cantonese version of the Mini-Mental State Examination. All patients were diagnosed based upon information obtained from clinical history and physical examination. The MR images were used to rule out other major neuropathologies. Imaging was performed on a 3 Tesla (Phillips) MRI system. An experienced radiologist reviewed the severity of white matter signal hyperintensities (WMSH) on MRI. Results. The main findings were: (i) FTD is associated with nonfluent and fluent aphasia, (ii) DAT is associated with memory disorder, (iii) FTD is associated with more extensive brain degradation than DAT. Conclusions. The regional brain alterations suggest that FTD and DAT are each associated with a characteristic distribution of clinical and neuropathological degradation. Brain imaging provides additional diagnostic information to distinguish DAT from FTD in Chinese speakers.