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Dementia and Aphasia-AD, FTD & Aphasia

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Dementia and Aphasia-AD, FTD & Aphasia 特別講演 Dementia and Aphasia-AD, FTD & aphasia Shunichiro Shinagawa, Bruce L. Miller Key words : Alzheimer’s disease, frontotemporal dementia, primary progressive aphasia Alzheimer’s disease（AD）and frontotemporal dementia（FTD）are two different type of neurodegenerative dementia, which can cause aphasic symptoms. Problems in memory, visuospatial are the predominant symptoms in AD, while behavioral and language manifestations are core features in FTD. There have been many changes is concept and history of primary progressive aphasia （PPA）, recent studies have divided the syndromes into three subtypes based on type of aphasia, distribution of atrophy, and underlying histopathology :（i）nonfluent variant PPA ;（ii）semantic variant PPA ; and（iii）the logopenic variant of PPA. Relationship between neurodegenerative dementia and PPA provides us a unique window into brain-behavior relations. （1）Alzheimerʼs disease and frontotemporal relatively preserved memory, which is different from dementia AD. Alzheimer’s disease（AD）is a progressive neurodegenerative disorder characterized by accu- （2）History of classification for aphasic mulation of amyloid plaques, neurofibrillary tangles, syndrome due to neurodegenerative and neuronal loss especially in posterior brain disease regions 1）. ADisthemostcommoncausesof Arnold Pick first described the relationship between dementia in adults over 65 years old ; problems in aphasia and dementia in clinical and anatomical paper memory, visuospatial navigation, reading and writing more than 100 years ago. He described the presenta- are the predominant symptoms. In contrast, fron- tion of focal language deterioration as a sign of a totemporal dementia（FTD）is one of the most dementia and helped to introduce the concept of a common forms of dementia in adults younger than 65 neurodegenerative disease beginning focally : “Sim- years, withfrontal and anterior temporal lobe ple progressive brain atrophy can lead to symptoms of predominant neurodegeneration due to several local disturbance through local accentuation of the pathologies 2）. Unique behavioral and language man- diffuse process” 3）. Sadly, these conditions did not ifestations are core features of FTD, which can be attract much researcher interest until recently. The divided into several clinical subtypes based on the revival of interest in these syndromes was indicated by early and predominant symptoms. Patients have a series of seminal papers by Brun and Gustafson, and Mesulam’s description of slowly progressive aphasia Memory & Aging Center, Department of Neurology, in 1982 4）; the syndrome with progressive aphasias University of California San Francisco, San Francisco, California, USA without dementia in their early stage. The term 認知神経科学 Vol. 15 No. 3 2014 165 subsequently renamed as Primary progressive aphasia Consequently, recent studies of PPA have divided （PPA）in 1987 5）. PPA is an impairment of language the syndromes into three subtypes :（i）nonfluent comprehension and expression without peripheral variant PPA（nfvPPA）, used to known as PNFA ;（ii） sensory and motor deficits. The language impairment semantic variant PPA（svPPA）, a used to known as must be insidiously progressive in nature to rule out SD ; and（iii）the logopenic variant of PPA（lvPPA） non-neurodegenerative causes suchas stroke or head used to known as LPA. trauma. The language disorder must be the primary deficit for about 2 years or more. （3）Three subtypes of PPA On the other hand, the selective degeneration of the These three subtypes are associated with different frontal and temporal regions, which can be related with localizations of cortical atrophy and with differences in behavioral and aphasic symptoms, gives rise to the pathological background. Figure 1 shows Character- term FTD. First, FTD divided into three subtypes by istic patterns of atrophy in the three variants of PPA. Neary et al. based on the early and predominant Voxel-based morphometry was used to identify symptoms in 1998 6）, : behavioral variant FTD regions where each variant showed volume loss （bvFTD）; semantic dementia（SD）, and progressive relative to controls（p < 0.05, corrected for multiple nonfluent aphasia（PNFA）. Patients withbvFTD comparisons）. Table 1 shows clinical features, present withmarked changesin personality and region of cortical atrophy, and most common behavior such as disinhibition, apathy, loss of underlying pathology of three variant of PPA. sympathy, compulsive behaviors, hyperorality. SD is characterized by a fluent anomic aphasia and behavior- （3-1）non-fluent variant Primary Progres- al changes. Patients with PNFA present slow, sive Aphasia effortful speech, impaired production and comprehen- nfvPPA is a progressive disorder of language sion of grammar. expression and motor speech 8）. Anatomically, it is For almost 2 decades, cases of PPA were generally associated with atrophy, hypometabolism and categorized as SD or PNFA within FTD spectrum. hypoperfusion of the left perisylvian area : frontal However, recent clinico-pathological researches re- operculum, premotor and supplementary motor areas vealed that there are many clinical subtypes in and anterior insula 10）. Patients present withslow, pathological proven AD cases, and FTD has many effortful speech, impaired production and comprehen- heterogeneous pathological backgrounds such as tau sion of grammar, and motor speechdeficits. Apraxia pathology, TDP-43（TAR DNA-binding protein 43） of speech, defined as difficulty initiating speech, a pathology, and FUS pathology 7）. Moreover, there slow rate of speechor incorrect sequencing or are some patients withprogressive language impair- omission of phonemes, is highly characteristic of ment who do not fit into the SD and PNFA of FTD nfvPPA, while dysarthria is more variably present. spectrum : a third, more recently defined subtype of Comprehension is spared for single words and for all primary progressive aphasia called as logopenic except the complex syntactic structures. Reading is progressive aphasia（LPA）8,9）. Patients withLPA non-fluent and effortful, while writing is agrammatic have impaired word-finding withhesitantspeechand and features phonemic paraphasias. impaired repetition. In addition to the aphasia, neuropsychological tests 166 Japanese Journal of Cognitive Neuroscience may show mild deficits in executive function, with （3-2）semantic variant Primary Progressive relatively spared episodic memory and visuospatial Aphasia function. Behavioral disturbances are less frequent svPPA is characterized by a fluent, anomic aphasia and severe than in bvFTD and svPPA, reflecting less and behavioral changes with remarkable, often damage in the orbitofrontal areas and the right asymmetric degeneration of the anterior temporal hemisphere in general 11）. Pathologically, nfvPPA is lobes 12）. Patients withprimarily left -sided predomi- usually associated witha tauopathybut occasionally nant atrophy present initially with progressive loss of other pathologies. word knowledge and meaning about words, objects and concepts ; so called ‘semantic’ knowledge. This is obvious as a fluent aphasiawithpoor speechcontent and semantic paraphasic errors, but intact syntax, prosody and motor speech, which may not be meaningful. When the disease disproportionately involves the right temporal lobe, deficits in knowledge of facial emotion, diminished recognition of familiar faces and deficits in empathy for others predominant the clinical syndrome. Anomia is the most common symptom. The inability to name an object is matched by the patient’s inability to give a detailed description of the object. In addition, patients withsvPPA havea multimodal agnosia and are unable to recognize word meanings via Figure 1. Characteristic patterns of atrophy in the three written, auditory, olfactory and visual modalities 13）. variants of PPA Reprinted from Gorno-Tempini et Patients withsvPPA present a surface dyslexia while al.（2004） Table 1. Clinical features, distribution of atrophy and underlying pathology of three variant of primary progressive aphasia most common clinical features region of cortical atrophy underlying pathology Poor confrontation naming semantic variant PPA Anterior and ventral temporal lobe FTLD-TDP Impaired single-word comprehension Effortful speechwithspeechsound errors non-fluent variant PPA Left inferior frontal and insula FTLD-tau Grammatical errors in language production Impaired single-word retrieval Left posterior temporal and inferior logopenic variant PPA Impaired repetition of phrases and sent- AD parietal ences PPA : primary progressive aphasia AD : Alzheimer’s disease FTLD-tau : frontotemporal lobar degeneration withtau -positive pathology FTLD-TDP : frontotemporal lobar degeneration withTDP43 -positive pathology 認知神経科学 Vol. 15 No. 3 2014 167 reading ; a condition in which the patient has phrase repetition is characteristically impaired, while difficulty reading words withirregular pronunciations, reproduction of short, single words can be spared. for example, yacht is pronounces “ya-ch”. These This same mechanism can cause impairment in language symptoms are known more generally as sentence comprehension, which is influenced more by “Gogi（word-meaning）aphasia” in Japan. Two lengthand probability of a sentence than by its systems of letters were used in writing Japanese, Kana grammatical complexity. （phonogram）and Kanji（phonogram）. svPPA pa- Imaging abnormalities in the left temporoparietal tients is not impaired at reading of Kana because of its junction area, left posterior superior temporal,
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