Frontotemporal Lobar Degeneration: A Clinical Approach
Frontotemporal Lobar Degeneration: A Clinical Approach
In 1892, Arnold Pick described patients with presenile dementia, aphasia, and lobar atrophy. This entity was subsequently referred to as Pick disease, and the characteristic inclusion bodies associated with this condition, identified by Alois Alzheimer in 1911, were named Pick bodies in Pick's honor. In 1957, Delay, Brion, and Escourolle and in 1974 Constantinidis, Richard, and Tissot delineated the clinical and anatomical differences between Alzheimer disease (AD) and Pick disease, emphasizing that atrophy in Pick disease was frontally predominant, while in AD more posterior. Their classification schemas recognized that there were prominent extrapyramidal syndromes associated with Pick disease and that only a minority of cases had classic Pick bodies. In 1982, Marsel Mesulam identified aphasia syndromes in patients with left-predominant hemispheric atrophy, collectively termed PPA (now including nfvPPA, svPPA, and logopenic variant PPA [lvPPA]). Though Pick's first cases would currently be classified as svPPA of left-predominant atrophy (l-svPPA), in the past "Pick dementia" was considered synonymous to what is now called bvFTD. A right-predominant atrophy svPPA (r-svPPA) also exists and presents with early behavioral deficits, whereas its syndromic convergence and pathologic homology to l-svPPA allows both syndromes to be classified as svPPA (see below). Recent discoveries of specific proteinopathies (e.g., tau, TDP-43, FUS) as well as genetic mutations (e.g., GRN, MAPT, C9Orf72) has opened avenues for new therapeutic interventions.
Epidemiologically, FTLD incidence is three to four cases per 100,000 person-years, with an estimated 20,000 to 30,000 cases in the United States at a given moment. It is the third most common cause of degenerative dementia after AD and dementia with Lewy bodies, accounting for 5 to 10% of all pathologically confirmed cases. Additionally, it is the second most common presenile dementia in patients younger than 65 years old after AD. Tau-positive cases tend to exhibit older disease onset and slower progression than TDP-43 and FUS FTLD subtypes. Table 1 contains epidemiologic features of FTLD subtypes, recognizing that diagnosis in most studies was based on pre-2011 diagnostic criteria.
Historical Perspective and Epidemiology
In 1892, Arnold Pick described patients with presenile dementia, aphasia, and lobar atrophy. This entity was subsequently referred to as Pick disease, and the characteristic inclusion bodies associated with this condition, identified by Alois Alzheimer in 1911, were named Pick bodies in Pick's honor. In 1957, Delay, Brion, and Escourolle and in 1974 Constantinidis, Richard, and Tissot delineated the clinical and anatomical differences between Alzheimer disease (AD) and Pick disease, emphasizing that atrophy in Pick disease was frontally predominant, while in AD more posterior. Their classification schemas recognized that there were prominent extrapyramidal syndromes associated with Pick disease and that only a minority of cases had classic Pick bodies. In 1982, Marsel Mesulam identified aphasia syndromes in patients with left-predominant hemispheric atrophy, collectively termed PPA (now including nfvPPA, svPPA, and logopenic variant PPA [lvPPA]). Though Pick's first cases would currently be classified as svPPA of left-predominant atrophy (l-svPPA), in the past "Pick dementia" was considered synonymous to what is now called bvFTD. A right-predominant atrophy svPPA (r-svPPA) also exists and presents with early behavioral deficits, whereas its syndromic convergence and pathologic homology to l-svPPA allows both syndromes to be classified as svPPA (see below). Recent discoveries of specific proteinopathies (e.g., tau, TDP-43, FUS) as well as genetic mutations (e.g., GRN, MAPT, C9Orf72) has opened avenues for new therapeutic interventions.
Epidemiologically, FTLD incidence is three to four cases per 100,000 person-years, with an estimated 20,000 to 30,000 cases in the United States at a given moment. It is the third most common cause of degenerative dementia after AD and dementia with Lewy bodies, accounting for 5 to 10% of all pathologically confirmed cases. Additionally, it is the second most common presenile dementia in patients younger than 65 years old after AD. Tau-positive cases tend to exhibit older disease onset and slower progression than TDP-43 and FUS FTLD subtypes. Table 1 contains epidemiologic features of FTLD subtypes, recognizing that diagnosis in most studies was based on pre-2011 diagnostic criteria.
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