How to diagnose and treat the easily overlooked culprit of dementia "frontotemporal degeneration"?

*Only for medical professionals to read and refer to the NCN 2021 exciting content express, not to be missed.
In the field of dementia, everyone's understanding of Alzheimer's disease is gradually deepening, but there is insufficient understanding of frontotemporal degeneration, another important cause of dementia
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The 24th National Neurology Conference of the Chinese Medical Association gave us the opportunity to learn about frontotemporal degeneration——Professor Yu Jintai from the Huashan Hospital affiliated to Fudan University gave a wonderful report on the diagnosis and treatment of frontotemporal degeneration.

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Part 1 basic concept: frontotemporal lobar degeneration ≠ frontotemporal dementia (frontotemporal lobar degeneration, FTLD) and frontotemporal dementia (frontotemporal dementia, FTD) are not completely equivalent concepts
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The difference between the two concepts is only two words, and it is very easy for everyone to confuse
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FTLD is a group of neurodegenerative diseases characterized by selective progressive atrophy and degeneration of the frontal and/or temporal lobes, which are clinically, pathologically and genetically heterogeneous
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Among neurodegenerative dementias under 65, FTLD is the second cause after Alzheimer's disease
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The following figure (Figure 1) summarizes the scope of FTLD, and the pathological proteins, pathological changes and related pathogenic genes corresponding to each phenotype can be clearly seen
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From the clinical phenotype, the frontotemporal lobe degeneration spectrum disease includes the following 7 types: (1) Amyotrophic lateral sclerosis: amyotrophic lateral sclerosis, ALS
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(2) FTD with concurrent motor neuron disease: FTD with concurrent motor neuron disease, FTD-MND
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(3) Semantic variant primary progressive aphasia: semantic variant primary progressive aphasia, svPPA
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(4) Behavior variant FTD: behavioral variant FTD, bvFTD
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(5) Nonfluent variant primary progressive aphasia: nonfluent variant primary progressive aphasia, nfvPPA
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(6) Corticobasal degeneration: corticobasal degeneration, CBD
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(7) Progressive supranuclear palsy: progressive supranuclear palsy, PSP
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Figure 1: Frontotemporal degeneration category [1] Frontotemporal dementia, or FTD, is a group of dementia syndromes with progressive mental behavior abnormalities, executive dysfunction, and language dysfunction as the main clinical manifestations.
Its pathological characteristics are selective Progressive atrophy of the frontal and/or temporal lobes, including bvFTD, svPPA and nfvPPA
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Figure 1 circles the types included in FTD, and it can be seen that FTD is a subset of FTLS
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FTD is a dementia syndrome, and frontotemporal degeneration has a motor symptom syndrome in addition to dementia syndrome
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Part 2 Epidemiology and survival of FTLD FTLD is a large group of diseases that are common but easily overlooked by everyone
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Among the various types of FTLD, everyone is familiar with ALS.
In fact, the incidence of PSP is dozens of times that of ALS
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However, in clinical work, doctors often lack knowledge of PSP, and patients with PSP are often diagnosed with diseases such as Parkinson's syndrome
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Although there is currently no FTLD epidemiological data in China, the 2016 Neurology magazine published an epidemiological study of 1.
69 million FTLDs in 2 regions in the UK, which shows that FTLD is more common (Figure 2) [2]
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The study also shows the survival period of various types of FTLD.
It can be seen that svPPA has the longest survival period and PSP has the shortest survival period, as shown in Figure 3 [2]
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Figure 2: Epidemiological survey of FTLD in two regions of the UK: A: number of patients per 100,000; B: age distribution; C: distribution of various types of FTLD by age; D: total number of patients of various types of FTLD[2] Figure 3: Survival period of each type of FTLD (blue: time from onset to diagnosis of neurodegenerative disease; yellow: time to specific diagnosis of FTLD; green: time to death) Part 3 FTLD clinical pathology Phenotype, imaging characteristics, pathological characteristics, and genetic aspects to understand the clinicopathological conditions and associations of FTLD
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The clinical phenotype spectrum of FTLD can be divided into three categories: behavioral and executive dysfunction, language dysfunction, and motor dysfunction
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The specific clinical phenotypes under each category are shown in Figure 4
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Figure 4: FTLD clinical phenotype spectrum (picture from Professor Yu Jintai PPT) Many clinical phenotypes of FTLD often have characteristic imaging features
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For example, bvFTD is manifested as atrophy of the frontal temporal lobe; nfvPPA is manifested as atrophy of the posterior frontal lobe and insular lobe, and is asymmetric; svPPA is often atrophy of the temporal pole of the dominant hemisphere; the right variant svPPA is manifested as a non-dominant hemisphere Significant atrophy; PSP can be manifested as a hummingbird sign
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These types of imaging manifestations are shown in Figure 5
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Figure 5: Some FTLD-type MRI findings (picture from Professor Yu Jintai's PPT) FTLD pathological changes include Tau protein, sarcoma fusion RNA binding protein (RNA-binding protein fused in sarcoma, FUS) and DNA binding protein-43 (transactive response) DNA-binding protein 43, TDP-43) and so on
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The clinical and pathological correspondences of FTLD are intricate (Figure 6).
The same pathological change can correspond to multiple clinical phenotypes; the same clinical phenotype may also correspond to multiple pathological changes; clinical inference through pathological changes or pathological inference through clinical It is very difficult to change
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Figure 6: The clinical and pathological correspondence between FTLD is intricate [3] 30%-50% of FTLD is related to genes.
Genetic factors play an important role in the pathogenesis of FTLD.
Common genes include MAPT, GRN, C9orf72 and so on
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Unlike other types of dementia, if FTLD is suspected, it is often necessary to advise patients to undergo genetic testing
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After reviewing the correspondence between FTLD genes, pathology and clinical phenotypes, it can be found that the correspondence between FTLD genes and pathology is better (Figure 7)
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The clinical research of FTLD abroad is mostly based on the classification of the gene phenotype
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There is a huge population size behind common diseases, and research results may benefit more people.
Therefore, in addition to genetic research on rare diseases of the nervous system, genetic research on common diseases should also be strengthened
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Figure 7: The corresponding relationship between FTLD gene and pathology is good.
[4] In terms of the therapeutic drug treatment of Part 4FTLD, the US FDA has not approved any drugs for the treatment of FTLD.

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The drug treatment of FTLD is mainly aimed at symptomatic treatment of behavioral, motor and cognitive disorders
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The effectiveness and adverse reactions of some drugs are shown in Figure 8.
In clinical practice, the medication should be selected based on the specific types of patients and the characteristics of the drugs
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It can be seen that a clear diagnosis is the cornerstone of subsequent drug treatment
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The clinical manifestations of FTLD follow a trend from asymptomatic to mild symptoms to typical symptoms
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Therefore, in terms of treatment, different treatments need to be given according to the stage of the disease: active prevention when asymptomatic, disease modification treatment when there are pathophysiological changes, and symptomatic treatment at the late stage
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Figure 8: Summary of drug effectiveness and adverse reactions: Professor Yu systematically explained the concept, pathology, epidemiology, clinical pathology, and treatment of FTLD.
Each part is interlocked, with both basic knowledge and international research.
And cutting-edge progress
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After reading this article, I believe you have a better understanding of FTLD
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At this annual meeting, Professor Yu Jintai also shared the "Interpretation of the 2021 Expert Consensus on the Management of Post-Stroke Cognitive Impairment" on the "Famous Doctor Kung Fu Tea" column of the medical doctor station
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Welcome to the medical doctor station to watch it .

Expert profile Professor Yu Jintai, young Yangtze River scholar of the Ministry of Education, professor, chief physician, doctoral supervisor, outstanding talent of Fudan University, executive deputy director of the Institute of Neurology of Fudan University, leader of the cognitive sub-specialty of the Department of Neurology of Huashan Hospital, currently Served as a national committee member of the Behavioral Medicine Branch of the Chinese Medical Association, the deputy head of the Neuropsychology and Behavior Group of the Chinese Medical Association Neurology Branch, the deputy editor-in-chief of the SCI journal Ann Transl Med, and the senior editorial board member of J Alzheimers Dis
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Presided over a number of general and major projects of the National Natural Science Foundation of China, led the formulation of Alzheimer's evidence-based prevention international guidelines, and published many academic papers in top journals such as Lancet Neurology and Alzheimers Dement
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References: [1]Meeter LH,Kaat LD,Rohrer JD,van Swieten JC.
Imaging and fluid biomarkers in frontotemporal dementia.
Nat Rev Neurol.
2017;13(7):406-419.
[2]Coyle-Gilchrist IT, Dick KM,Patterson K,et al.
Prevalence,characteristics,and survival of frontotemporal lobar degeneration syndromes.
Neurology.
2016;86(18):1736-1743.
[3]Olney NT,Spina S,Miller BL.
Frontotemporal Dementia.
Neurol Clin.
2017;35(2):339-374.
[4]Sieben A,Van Langenhove T,Engelborghs S,et al.
The genetics and neuropathology of frontotemporal lobar degeneration.
Acta Neuropathol.
2012;124(3):353- 372.
The content of this article is compiled from the lecture of Professor Yu Jintai at the 24th National Neurology Conference of the Chinese Medical Association-"Clinical Diagnosis and Treatment Practice of Frontotemporal Degeneration"
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