Frontotemporal dementia: Past, present, and future.

INTRODUCTION: The history of frontotemporal dementia (FTD) is both old and new. This study explores its historical roots, dating back to the 19th century, while recognizes it as a distinct neurological entity only a few decades ago. METHODS: This qualitative study and literature review provides an overview of FTD's historical background, birth, evolution, and future directions. RESULTS: Recognition of FTD was hindered by rigid perceptions of dementia, the division between neurology and psychiatry, reliance on IQ-based assessment, limited neuroimaging capabilities, and lack of pathological proof. Overcoming these barriers involved revisiting early pioneers' approaches, focusing on focal impairment, establishing non-Alzheimer's disease cohorts, fostering collaboration, and developing diagnostic criteria. Current gaps include the need for biology-oriented psychiatry education, biological biomarkers, and culturally sensitive, objective clinical instruments predicting underlying pathology. DISCUSSION: Independent multidisciplinary centers are essential. The future of FTD lies in disease-modifying therapies, presenting new opportunities for healthcare professionals and researchers.

History of Pick's disease.

After a short summary of Arnold Pick's biography, the history of how Pick's disease (PiD) was reported is presented, from its clinical symptoms to its molecular characterization. The macroscopic description of frontotemporal atrophy by Pick is recounted followed by a description of the histological lesions observed by Alzheimer and the progressive characterization of the disease. The subsequent diagnosis has since relied on ultrastructural findings as well as immunohistochemical and biochemical techniques. The discovery of the role of the microtubule-associated τ-protein, encoded by chromosome 17, more specifically of the 3R isoform, has led to the inclusion of PiD in the 3R tauopathies. Today, both sporadic and familial PiDs, including the more frequent behavioral form, are considered as frontotemporal dementias. Experimental models have reproduced some of the lesions but the prion-like hypothesis concerning PiD has not, as yet, been proven.

[From Arnold Pick's original descriptions to frontotemporal dementia: the present enlightened by the past an historical approach]. / Des observations originales d'Arnold Pick à la démence frontotemporale : regard sur le présent à partir du passé Un aperçu historique.

Since its seminal characterization, Pick's disease (PiD), was marked by a double ambiguity. Sometimes, with reference to original Pick's descriptions, PiD was macroscopically defined by a circumscribed frontotemporal cerebral atrophy, independently of its causes. Sometimes, on the other hand, it was histologically characterized by absence of Alzheimer pathology and considered as a special form of degenerative process. However, this special degenerative process was defined either by the particular topography of neuronal loss or by specific histological changes, which were described by Alzheimer. Therefore, individualization of PiD and its relationships with Alzheimer's disease have long been controversial, particularly in the United States, despite the clarification provided by French authors in the 1960s, Swiss authors in the 1970s and Swedish and English authors in the 1980s. The term of Frontotemporal dementia (FTD) was choosed by the last authors in 1994 to avoid the debates on the definition of PiD, and to characterize a particular degenerative process without Alzheimer pathology or other diseases. However, the definition and nature of FTD currently remain ambiguous because the term FTD is applied either to clinical syndromes with different presentations according to predominant frontal or temporal atrophy, and regardless of histologic pathology, or to a particular degenerative process, hereditary or sporadic. Notwithstanding neuropathologic and genetic advances in the last decades, significant challenges remain for FTD therapeutic research as a result of the degenerative processes complexity and lack of parallelism between clinical, neuropathological, and genetic data.

'Limits and current knowledge of Pick's disease: its differential diagnosis'. A translation of the 1957 Delay, Brion, Escourolle article.

This article is a translation of a French article by Delay, Brion, and Escourolle. In a seminal article published in French in 1957 these authors summarized the work of previous researchers and reviewed a wide sample of frontotemporal dementia (FTD) cases formerly referred to as Pick's disease. The authors were among the first to define the critical clinical and anatomical differences between Alzheimer's disease (AD) and FTD and they even delineated distinctive FTD subtypes making possible the advances that now constitute the base of our studies. Reviewing their work allows us to appreciate the progress research has made.

Episodic memory in frontotemporal dementia: a critical review.

This review offers a critical appraisal of the literature on episodic memory performance in frontotemporal dementia. Historically, description of patients diagnosed with what was then known as Pick's disease included the presence of memory deficits and an underlying amnestic syndrome was noted in some of these patients. Over the last 20 years, however, the clinical view has been that episodic memory processing is relatively intact in the frontotemporal dementia syndrome. In particular, patients with the subtypes of behavioural variant frontotemporal dementia and progressive non-fluent aphasia are reported to perform within normal limits on standard memory tests. In the third clinical presentation of frontotemporal dementia, semantic dementia, relatively intact episodic memory against a significantly impaired semantic memory was regarded as the hallmark. This position was instrumental in the development of clinical diagnostic criteria for frontotemporal dementia in which amnesia was explicitly listed as an exclusion criterion for the disease. The relative intactness of episodic memory, therefore, appeared to be a useful diagnostic marker to distinguish early frontotemporal dementia from Alzheimer's disease, in which early episodic memory disturbance remains the most common clinical feature. We argue that recent evidence questions the validity of preserved episodic memory in frontotemporal dementia, particularly in behavioural variant frontotemporal dementia. In semantic dementia, a complex picture emerges with preservation of some components of episodic memory, notably recognition-based visual memory and recall of recent autobiographical events. We propose a critical synthesis of recent neuropsychological evidence on retrograde and anterograde memory in light of neuroimaging and neuropathological findings, demonstrating involvement of medial temporal structures in frontotemporal dementia, structures known to be critical for episodic memory processing. We further argue that the multifactorial nature of most memory tests commonly used clinically fail to capture the memory deficits in frontotemporal dementia and that sensitive assessment tools of memory are needed. Together, recent clinical and experimental findings and the historical evidence represent a strong case for a re-evaluation of the importance of memory disturbance in the clinical diagnosis of frontotemporal dementia.

The birth and early evolution of the frontotemporal dementia (FTD) concept.

An historical overview of the development of the concept of frontotemporal dementia is presented, regarding the last 30 years, using as a backbone the conferences held on this theme, with a start in 1986 in Lund, Sweden. Since then, a dramatic increase in research activities and publications has rapidly expanded our knowledge in this field, a step necessary for the ultimate goal to find an effective treatment of this devastating disorder.

Argentina's early contributions to the understanding of frontotemporal lobar degeneration.

Over a 100 years have passed since Pick's description of what is now termed frontotemporal lobar degeneration (FTLD). FTLD is a topic of intense current research interest yet some relevant contributions by non-English speaking authors have received little attention, which makes the history of FTLD research incomplete. In the hopes of filling some of the gaps in the history of FTLD research, the present article introduces fundamental work carried out in Argentina during the first half of the 20th century by Christfried Jakob and Braulio A. Moyano. Jakob's neurophilosophy, as well as his empirical descriptions on dementia and theoretic insights into the role of the frontal lobes are highlighted. Moyano's works on frontotemporal dementia (FTD), specifically concerning language deficits and the concept of focal pathology in Alzheimer disease presenting with progressive aphasia are introduced. These early contributions are examined in the light of the current knowledge on FTLD, highlighting some of the authors' early original contributions, as well as their misconceptions. These authors remain largely unknown despite the fact that their contributions were fundamental in kindling interest in behavioral neurology in Latin America, which continues to this day.

[Amusia and aphasia of Bolero's creator--influence of the right hemisphere on music]. / Amuzija i afazija tvorca Boléra--utjecaj desne hemisfere na glazbu.

OBJECTIVES: The experience with cortical localization (BA 44, 45, 22) of language (Broca, Wernicke and others) in the left hemisphere has been repeatedly tested over the last 150 years and is now generally accepted. A single case report with autopsy findings (Leborgne, Tan tan), has enabled to localize the seat of spoken language in the left third frontal convolution. As music and language have a lot in common and even share the same hearing system, it is logical to try to localize the cognitive centers for music too. METHODS: The disabling neurological disease illness of Maurice Ravel (1875-1937), a French impressionist composer, is not the right example to localize music center as that of Broca's language center, but it demonstrates the role of the right hemisphere in music production. In the last five years of his life, Ravel suffered from an unknown disease that affected the left hemisphere causing aphasia, apraxia, alexia, agraphia and amusia. It was the reason why Ravel could not compose during the last years of his life. In contrast to Ravel, Shebalin and Britten continued writing music works of their own although aphasic after having sustained two strokes to the left hemisphere. While lacking clinical cases with selective ablative brain lesions, research into the music localization can be done using modern imaging technologies such as fMRI and PET. RESULTS: Exercising music (professionally) develops analytical process in the left hemisphere whereas other individuals process music in their right hemisphere. There is right ear (left hemisphere) predominance in musicians and vice versa in musical amateurs. Music lateralization towards the right hemisphere is seen in women and in inattentive listeners. It can be subject to cultural influence, so the Japanese process their traditional popular music in the left hemisphere, whereas Westerners process the same music in the right hemisphere. Music and language are processed separately; they are localized in homologous regions of the opposite hemispheres. In 1937, Ravel underwent neurosurgical procedure performed by Vincent; autopsy was not done. It is believed that the cause of hi disease was primary progressive aphasia associated with Pick's disease. CONCLUSION: Boléro and Concerto for the Left Hand were the last Ravel's works (the onset of his disease), so it is possible that the projected the influence of the healthy right hemisphere onto his music (and on the creative process) because Ravel's left hemispher was damaged. Indeed, in these last music works one can feel the predominance of changes in pitch (timbre), i. e. right hemisphere, in comparison to only few changes of melody (left hemisphere).

Pick complex--historical introduction.

This historical summary follows the major conceptual developments of the cohesive rather than the fractionated view of the disease, named after Pick. Clinical and biologic evidence in favor the entity is discussed. The changing and proliferating knowledge and terminology requires the integration of several levels of descriptions, while keeping the work in the past in sight. A historical perspective helps to prevent the chaos of terminological confusion and reinventing the wheel.

Frontotemporal dementia--Part I. History, prevalence, clinical forms.

The authors report a comprehensive publication consisting of three parts going into the details of history, prevalence, clinical forms, differential diagnosis, genetics, molecular pathomechanism, pathology, clinical diagnosis and treatment of frontotemporal dementia (FTD). The first part of the present review deals with history, prevalence and clinical forms of FTD. The prototypical FTD with circumscribed atrophy was first described by Arnold Pick; Alois Alzheimer found the intraneural inclusions in the patients' brain. Later it was recognised that many patients had neither the atrophy nor the cellular changes, but genetic mutations have been identified. Frontotemporal dementia is a degenerative condition with unknown etiology in the frontal and anterior temporal lobes of the brain. It is a progressive neurobehavioral syndrome characterized by early decline in social interpersonal conduct, early impairment in the regulation of personal conduct, early emotional blunting, and early loss of insight. There are no reliable epidemiological studies on the prevalence of FTD, but it is well-accepted that FTD is a common cause for dementia before the age of 65 (it constitutes approximately five percent of all irreversible dementias). The nomenclature of the FTD has been confusing and continues to be. Three major clinical syndromes can be identified: 1 frontal variant FTD (dementia of frontal type) in which changes in social behavior and personality predominate, 2. in semantic dementia (progressive fluent aphasia) there is a breakdown in the conceptual database which underlies language production and comprehension, 3. in progressive nonfluent aphasia the phonologic and syntactic components of language are affected. The authors report two cases, which can point to clinical symptoms and forms, and mention the problems of the differential diagnosis and therapy.

Arnold Pick's concept of dementia.

Arnold Pick (1851-1924) provided the first description of the neurodegenerative disease associated with his name; but his importance to the field of neuroscience goes far beyond this eponymous gift. His view that the process of dementia should be seen as a mosaic of circumscribed neuropsychological deficits and not as a diffuse degradation of mental abilities is essential for progress in a cognitive neuropsychological approach to the study of dementias.

The exceptional brain of Maurice Ravel.

This historical review describes the brain disease which afflicted the great impressionist-classicist composer Maurice Ravel (1875-1937). The usual interpretation of the symptoms Ravel exhibited during his disease is primary progressive aphasia / Pick's disease. Some authors see this as the cause for his lost musical creativity during the last years of his life. By contrast, in our review it is presented why a car accident in 1932, with the probable consequence of a mild to moderate traumatic brain injury, could be the key event in his life, triggering the loss of his ability to compose. In addition, the influence of Ravel's disease on his musical style is evaluated. Although some authors see a link, we try to explain why there is no clear evidence for this.

[Early history of Pick's disease]. / Zur Frühgeschichte der Pickschen Erkrankung.

The development of the concept of Pick's disease can be divided into three periods. From 1892 on Arnold Pick reported a series of patients presenting cognitive disturbances, personality changes and focal symptoms such as aphasia and apraxia. Pick, however, like his contemporaries, did not conceive of a new nosological entity. The major event during the second period was the outline of histological characteristics like argentophilic inclusion bodies by Alois Alzheimer. During the 1910s however, Alzheimer's extremely important observation remained unnoticed. Further historical research is necessary to clarify why Alzheimer's subtype of dementia was hurriedly regarded as a disease, whereas Pick's was not. Political factors such as Kraepelin's strategic considerations seem to have played an essential role. In accordance with major research criteria of German neuropsychiatry, Pick's atrophy was constructed as a full-blown disease entity in the 1920s. This concept gained acceptance in the German and Anglo-American scientific community and was the starting point for further investigations in the 1950s and 1960s.

[The importance of Arnold Pick for modern concepts of degenerative dementia. Retrospect and appreciation]. / Die Bedeutung Arnold Picks für moderne Konzepte degenerativer Demenzen. Erinnerung und Würdigung.

It will be shown that the contribution of Arnold Pick (1851-1924) goes far beyond the first description of the disorder associated with his name. His view that the process of dementia should not be conceptualised as a diffuse degradation of mental abilities but as a mosaic of circumscribed neuropsychological deficits is as modern now as it was then and is a prerequisite for the differential diagnosis of degenerative dementias during life.