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Distinguishing Frontotemporal Dementia From Alzheimer Disease Through Everyday Function Profiles: Trajectories of Change.

ABSTRACT: Background: Different dementia syndromes display different patterns of everyday functioning. This article explored different patterns of functioning at baseline and trajectories of change in behavioral variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD).

Methods: Data from the Uniform Data Set of the National Alzheimer's Coordinating Centre were employed. The Functional Assessment Questionnaire assessed functioning at up to 7 follow-up visits. Independent t tests assessed variations in functioning between syndromes at baseline. Linear mixed-effect modeling explored longitudinal functional trajectories between syndromes.

Results: Data from 3351 patients (306 bvFTD and 3,045AD) were analyzed. At baseline, patients with bvFTD performed all daily activities poorer than AD dementia. Linear mixed models showed a significant effect of syndrome and time on functioning, and evidence of interaction between syndrome and time, with bvFTD showing a steeper decline for using the stove and travel.

Conclusions: Findings can help in the effective care planning of everyday functioning for bvFTD and AD dementia.

SUBMITTER: Giebel CM

PROVIDER: S-EPMC7423644 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Distinguishing Frontotemporal Dementia From Alzheimer Disease Through Everyday Function Profiles: Trajectories of Change.

Giebel Clarissa M CM Knopman David D Mioshi Eneida E Khondoker Mizanur M

Journal of geriatric psychiatry and neurology 20200213 1

<h4>Background</h4>Different dementia syndromes display different patterns of everyday functioning. This article explored different patterns of functioning at baseline and trajectories of change in behavioral variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD).<h4>Methods</h4>Data from the Uniform Data Set of the National Alzheimer's Coordinating Centre were employed. The Functional Assessment Questionnaire assessed functioning at up to 7 follow-up visits. Independent <i>t</i> tes ...[more]

PMID: 32054376

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Project description:IMPORTANCE:Neurodegenerative diseases can cause dysfunction of neural structures involved in judgment, executive function, emotional processing, sexual behavior, violence, and self-awareness. Such dysfunctions can lead to antisocial and criminal behavior that appears for the first time in the adult or middle-aged individual or even later in life. OBJECTIVE:To investigate the frequency and type of criminal behavior among patients with a diagnosed dementing disorder. DESIGN, SETTING, AND PARTICIPANTS:We conducted a retrospective medical record review of 2397 patients who were seen at the University of California, San Francisco, Memory and Aging Center between 1999 and 2012, including 545 patients with Alzheimer disease (AD), 171 patients with behavioral variant of frontotemporal dementia (bvFTD), 89 patients with semantic variant of primary progressive aphasia, and 30 patients with Huntington disease. Patient notes containing specific keywords denoting criminal behavior were reviewed. Data were stratified by criminal behavior type and diagnostic groups. MAIN OUTCOMES AND MEASURES:Frequencies of criminal behavior and ?² statistics were calculated. RESULTS:Of the 2397 patients studied, 204 (8.5%) had a history of criminal behavior that emerged during their illness. Of the major diagnostic groups, 42 of 545 patients (7.7%) with AD, 64 of 171 patients (37.4%) with bvFTD, 24 of 89 patients (27.0%) with semantic variant of primary progressive aphasia, and 6 of 30 patients (20%) with Huntington disease exhibited criminal behavior. A total of 14% of patients with bvFTD were statistically significantly more likely to present with criminal behavior compared with 2% of patients with AD (P?<?.001) and 6.4% were statistically significantly more likely to exhibit violence compared with 2% of patients with AD (P?=?.003). Common manifestations of criminal behavior in the bvFTD group included theft, traffic violations, sexual advances, trespassing, and public urination in contrast with those in the AD group, who commonly committed traffic violations, often related to cognitive impairment. CONCLUSIONS AND RELEVANCE:Criminal behavior is more common in patients with bvFTD and semantic variant of primary progressive aphasia than in those with AD and is more likely to be an early manifestation of the disorder. Judicial evaluations of criminality in the demented individual might require different criteria than the classic "insanity defense" used in the American legal system; these individuals should be treated differently by the law. The appearance of new-onset criminal behavior in an adult should elicit a search for frontal and anterior temporal brain disease and for dementing disorders.

Project description:Information on circulating miRNAs in frontotemporal lobar degeneration is very limited and conflicting results have complicated an interpretation in Alzheimer's disease thus far. In the present study we I) collected samples from multiple clinical centers across Germany, II) defined 3 homogenous patient groups with high sample sizes (bvFTD n = 48, AD n = 48 and cognitively healthy controls n = 44), III) compared expression levels in both CSF and serum samples and IV) detected a limited set of miRNAs by using a MIQE compliant protocol based on SYBR-green miRCURY assays that have proven reliable to generate reproducible results. We included several quality controls that identified and reduced technical variation to increase the reliability of our data. We showed that the expression levels of circulating miRNAs measured in CSF did not correlate with levels in serum. Using cluster analysis we found expression pattern in serum that, in part, reflects the genomic organization and affiliation to a specific miRNA family and that were specifically altered in bvFTD, AD, and control groups. Applying factor analysis we identified a 3-factor model characterized by a miRNA signature that explained 80% of the variance classifying healthy controls with 97%, bvFTD with 77% and AD with 72% accuracy. MANOVA confirmed signals like miR-320a and miR-26b-5p at BH corrected significance that contributed most to discriminate bvFTD cases with 96% sensitivity and 90% specificity and AD cases with 89% sensitivity and specificity compared to healthy controls, respectively. Correlation analysis revealed that miRNAs from the 3-factor model also correlated with levels of protein biomarker amyloid-beta1-42 and phosphorylated neurofilament heavy chain, indicating their potential role in the monitoring of progressive neuronal degeneration. Our data show that miRNAs can be reproducibly measured in serum and CSF without pre-amplification and that serum includes higher expressed signals that demonstrate an overall better ability to classify bvFTD, AD and healthy controls compared to signals detected in CSF.

Dataset Information

Distinguishing Frontotemporal Dementia From Alzheimer Disease Through Everyday Function Profiles: Trajectories of Change.

Publications

Distinguishing Frontotemporal Dementia From Alzheimer Disease Through Everyday Function Profiles: Trajectories of Change.

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