Longitudinal cognitive biomarkers predicting symptom onset in presymptomatic frontotemporal dementia

Jiskoot, Lize C.; Panman, Jessica L.; Asseldonk, Lauren van; Franzen, Sanne; Meeter, Lieke H.H.; Kaat, Laura Donker; Ende, Emma L. van der; Dopper, Elise G.P.; Timman, Reinier; Minkelen, Rick van; Swieten, John C. van; Berg, Esther van den; Papma, Janne M.

doi:10.1007/s00415-018-8850-7

Cited by 55 publications

(85 citation statements)

References 54 publications

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“…MAPT mutation carriers were the only group impaired on both immediate and delayed recall at baseline, whereas GRN and C9orf72 mutation carriers were only impaired on immediate recall. This is in line with a previous study by Jiskoot et al [16] that demonstrated significant decline on the RAVLT recall test in the presymptomatic stage of MAPT mutation carriers, with a further decline in participants that converted to symptomatic FTD during follow-up. This is further corroborated by the finding that the RBMT direct and delayed recall trials were most sensitive to differentiate MAPT mutation carriers from non-carriers.…”

Section: Discussionsupporting

confidence: 93%

“…The most profound decline was seen on attention/mental processing speed and memory. Memory problems have previously been described in GRN as a symptom characterizing progressed disease stages [16], although it could also be associated with the profound impairment in attention/mental processing speed [31].…”

Section: Discussionmentioning

confidence: 96%

“…The former could be helpful in providing psycho-education and counseling to the patient and caregiver on the expected clinical presentation and disease course. Moreover, selection of the most sensitive tests per genetic defect enables shortening of the neuropsychological test battery thereby relieving patient burden [16]. Executive tasks, such as letter fluency, and tasks for attention and mental processing speed, such as TMT and SCWT, were most sensitive to detect GRN-associated FTD, whereas memory recall deficits seem a promising marker in MAPTassociated FTD.…”

Section: Discussionmentioning

confidence: 99%

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Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

et al. 2020

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Introduction Trials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify genespecific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations. Methods We examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described longitudinal (M = 22.6 months, SD = 16.6) data in a subsample (n = 27). Results Patients showed overall cognitive impairment, except memory recall, working memory and visuoconstruction. GRN patients performed lower on executive function (mean difference − 2.1; 95%CI − 4.1 to − 0.5) compared to MAPT and lower on attention compared to MAPT (mean difference − 2.5; 95%CI − 4.7 to − 0.3) and C9orf72 (mean difference − 2.4; 95%CI − 4.5 to − 0.3). Only MAPT patients were impaired on delayed recall (mean difference − 1.4; 95%CI − 2.1 to − 0.7). GRN patients declined rapidly on attention and memory, MAPT declined in confrontation naming, whereas C9orf72 patients were globally impaired but remained relatively stable over time on all cognitive domains. Discussion This study shows gene-specific cognitive profiles in bvFTD, which underlines the value of neuropsychological tests as outcome measures in upcoming trials for genetic bvFTD.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

et al. 2020

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“…This might suggest that additional frontal executive function in aMCI increases risk for AD rather than FTD. However, since frontal-executive dysfunction is a hallmark of FTD symptomatology and FTD may have a sneaky onset 13 , it is possible that these patients may develop FTD.…”

Section: Discussionmentioning

confidence: 99%

Frontal-executive dysfunction affects dementia conversion in patients with amnestic mild cognitive impairment

Jung

Park

Cho

et al. 2020

Sci Rep

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Among mild cognitive impairment (MCI) patients, those with memory impairment (amnestic MCI, aMCI) are at a high risk of dementia. However, the precise cognitive domain, beside memory, that predicts dementia conversion is unclear. Therefore, we investigated the cognitive domain that predicts dementia conversion in a longitudinal aMCI cohort. We collected data of 482 aMCI patients who underwent neuropsychological tests and magnetic resonance imaging at baseline and were followed for at least 1 year. The patients were categorized according to number (1-4) and type of impaired cognitive domains (memory, language, visuospatial, and frontal-executive function). We evaluated dementia conversion risk in each group when compared to single-domain aMCI after controlling for age, education, diabetes and dyslipidemia. Baseline cortical thickness of each group was compared to that of 410 cognitively normal controls (NCs) after controlling for age, intracranial volume, diabetes and dyslipidemia. Compared to single-domain aMCI, aMCI patients with frontal-executive dysfunction at baseline had a higher risk of dementia conversion than aMCI patients with visuospatial or language dysfunction. Compared to NCs, aMCI patients with frontal-executive dysfunction had overall cortical thinning including frontal areas. Our findings suggest that aMCI patients with frontal-executive dysfunction have poor prognosis and,thus, should be considered for intervention therapy with a higher priority among aMCI patients. Mild cognitive impairment (MCI) is a transitional state between normal aging and dementia. MCI patients show dysfunction in one or more of the four major cognitive domains, namely language, visuospatial, memory, and frontal-executive function. Among the MCI patients, it has been well established that those with memory impairment (amnestic MCI, aMCI) are at a high risk of dementia, especially Alzheimer's dementia (AD) type 1. Additionally, previous studies have reported that among aMCI patients, multiple-domain cognitively impaired patients have poor prognosis compared to single-domain memory impaired patients 2. However, which cognitive domain, beside memory, that predicts dementia or AD conversion is not well established 3. aMCI is a heterogenous group with varied phenotypes, pathologies, and prognoses. Many studies have attempted the to classify aMCI patients into homogenous groups using various tools 3,4. Neuropsychological test is a widely-used, simple tool that can be easily utilized by primary physicians. Thus, although AD biomarkers such

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“…However, measurable episodic memory impairment in bvFTD patients may be as severe as in the patients with AD [15,[39][40][41][42][43]. Memory deficits have also been noted in the clinical memory tests of bvFTD patients at the presymptomatic stage [44,45]. Relatively spared episodic memory is, however, considered as one of the main features suggestive for bvFTD in the prevailing diagnostic criteria [2].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Prodromal Symptoms of Patients with Behavioral Variant Frontotemporal Dementia and Alzheimer Disease

Korhonen

Katisko

Cajanus

et al. 2020

Dement Geriatr Cogn Disord

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Introduction: Behavioral variant frontotemporal dementia (bvFTD) is the most common clinical subtype of frontotemporal lobar degeneration. bvFTD is often characterized by changes in behavior and personality, frequently leading to psychiatric misdiagnoses. On the other hand, substantial clinical overlap with other neurodegenerative diseases, such as Alzheimer disease (AD), further complicates the diagnostics. Objective: Our aim was to identify the main differences in early symptoms of bvFTD and AD in the prodromal stages of the diseases. In addition, patients with bvFTD were analyzed separately according to whether they carry the C9orf72 repeat expansion or not. Methods: Patient records of bvFTD (n = 75) and AD (n = 83) patients were analyzed retrospectively for memory and neuropsychiatric symptoms, sleeping disorders, and somatic complaints before the setting of the accurate diagnosis. Results: A total of 84% of bvFTD patients (n = 63) and 98.8% of AD patients (n = 82) reported subjective memory disturbances in the prodromal phases of the disease. bvFTD patients presented significantly more often with sleeping disorders, headache, inexplicable collapses, transient loss of consciousness, somatization, delusions, and hallucinations, suicidality, changes in oral behaviors, and urinary problems. In addition, poor financial judgement was frequently detected in patients with prodromal bvFTD. Aberrant sensations in the nose and throat without any physical explanation, regarded as somatizations, emerged only in bvFTD patients with the C9orf72 repeat expansion. Conclusions: Subjective reporting of impaired episodic memory is a poor indicator in differentiating bvFTD from AD. Sleeping disturbances, delusions, hallucinations, and unexplained somatic complaints in a patient with cognitive disturbances should prompt the clinicians to consider bvFTD as a possible diagnostic option behind these symptoms. The spectrum of symptoms in the prodromal stages of bvFTD may be more diverse than the latest criteria suggest.

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Longitudinal cognitive biomarkers predicting symptom onset in presymptomatic frontotemporal dementia

Cited by 55 publications

References 54 publications

Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

Frontal-executive dysfunction affects dementia conversion in patients with amnestic mild cognitive impairment

Comparison of Prodromal Symptoms of Patients with Behavioral Variant Frontotemporal Dementia and Alzheimer Disease

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