Abstract
The presymptomatic stages of frontotemporal dementia (FTD) are still poorly defined and encompass a long accrual of progressive biological (preclinical) and then clinical (prodromal) changes, antedating the onset of dementia. The heterogeneity of clinical presentations and the different neuropathological phenotypes have prevented a prior clear description of either preclinical or prodromal FTD. Recent advances in therapeutic approaches, at least in monogenic disease, demand a proper definition of these predementia stages. It has become clear that a consensus lexicon is needed to comprehensively describe the stages that anticipate dementia. The goal of the present work is to review existing literature on the preclinical and prodromal phases of FTD, providing recommendations to address the unmet questions, therefore laying out a strategy for operationalizing and better characterizing these presymptomatic disease stages.
Highlights
Developing the framework of preclinical disease stages as well as mild cognitive and/or behavioral and/or motor impairment (MCBMI)-frontotemporal dementia (FTD) continues to pose a challenge, and two aspects should be considered for future studies
We should first carefully define the criteria of MCBMI, which may be conceptualized as a “risk state.”
MCBMI may represent the prodromal state of FTD, and in some cases, it may refer to a neuropsychiatric condition different from FTD, especially in late-onset cases in which different neuropathologies including Alzheimer’s disease (AD) may coexist, or to a non-progressive or reversible stage
Summary
Is there a “no disease” phase in genetic FTD preceding the onset of preclinical disease?. Present work is to review the existing literature on the preclinical and prodromal phases of FTD, discussing and proving recommendations to the nine pressing questions that need a proper definition (see Box 1). This provides a starting point for operationalizing and better characterizing preclinical and prodromal disease stages of FTD.
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