Distribution of brain atrophy in behavioral variant frontotemporal dementia

Kril, Jillian J.; Macdonald, Virginia; Patel, Smita S.; Png, Francoise Y.; Halliday, Glenda M.

doi:10.1016/j.jns.2005.02.003

Cited by 77 publications

(56 citation statements)

References 41 publications

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“…More importantly, the OFC region emerged as the most sensitive indicator of group membership: very few AD patients show atrophy of this brain region in the early stages of the disease, despite evidence of more generalized frontal atrophy [17,18]. The OFC region has been implicated in bvFTD on the basis of quantitative MRI measures [11], as well as by pathological studies [19]. Standardized neuropsychological tests which target the OFC region are rare.…”

Section: Discussionmentioning

confidence: 99%

Orbitofrontal Dysfunction Discriminates Behavioral Variant Frontotemporal Dementia from Alzheimer’s Disease

Hornberger

Savage

Hsieh

et al. 2010

Dement Geriatr Cogn Disord

100

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Background: Behavioral variant frontotemporal dementia (bvFTD) patients show prefrontal cortex dysfunction and atrophy. Methods: We investigated whether executive function in conjunction with prefrontal cortex atrophy discriminates bvFTD and Alzheimer’s disease (AD) patients efficiently at presentation. Results: AD and bvFTD patients were distinguishable by 89.5% on their performance of 3 executive tasks: the Hayling Test of Inhibitory Control, Digit Span Backward and Letter Fluency. Similarly, scan ratings showed that orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex regions distinguish both patient groups. More importantly, employing the Hayling error score in conjunction with the OFC atrophy rating showed that 92% of patients can be correctly classified into bvFTD and AD. Conclusion: A combination of OFC and disinhibition measures appears to be a powerful diagnostic tool in differentiating bvFTD from AD patients in this preliminary study.

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Section: Discussionmentioning

confidence: 99%

Orbitofrontal Dysfunction Discriminates Behavioral Variant Frontotemporal Dementia from Alzheimer’s Disease

Hornberger

Savage

Hsieh

et al. 2010

Dement Geriatr Cogn Disord

100

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“…However, somewhat counterintuitively, we observed parietal lobe atrophy yet functional connectivity increases in bvFTD. Since parietal lobe is not commonly an early site of pathologic damage in bvFTD, 34 atrophy is largely due to spreading of disease from the pathologically damaged frontal and temporal lobes. 34 Increased functional connectivity in this region is likely due to a disconnection from pathologically affected salience regions.…”

mentioning

confidence: 99%

“…Since parietal lobe is not commonly an early site of pathologic damage in bvFTD, 34 atrophy is largely due to spreading of disease from the pathologically damaged frontal and temporal lobes. 34 Increased functional connectivity in this region is likely due to a disconnection from pathologically affected salience regions. Therefore, atrophy and increased functional connectivity in this region may be resulting independently from pathologic changes occurring elsewhere in the brain.…”

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confidence: 99%

Altered functional connectivity in asymptomatic MAPT subjects

Josephs²,

et al. 2011

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Objective: To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD). Methods:In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest. Results:The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects. Conclusions:Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease. Neurology ® 2011;77:866-874 GLOSSARY AD ϭ Alzheimer disease; BOLD ϭ blood oxygenation level-dependent; bvFTD ϭ behavioral variant frontotemporal dementia; DMN ϭ default mode network; FOV ϭ field of view; FTD ϭ frontotemporal dementia; FWE ϭ familywise error; ICA ϭ independent component analysis; MPRAGE ϭ magnetization-prepared rapid acquisition gradient echo; PPND ϭ pallido-ponto-nigral degeneration; ROI ϭ region of interest; TE ϭ echo time; TIV ϭ total intracranial volume; TR ϭ repetition time.Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder characterized by behavioral and language deficits.1,2 A large proportion of subjects with FTD have an autosomal dominant pattern of inheritance, 3,4 with many showing mutations in the microtubule associated protein tau (MAPT) gene.5 Subjects with mutations in MAPT typically present with behavioral variant FTD (bvFTD), with poor semantic abilities, 6 -8 and show predominant temporal atrophy, with less severe involvement of frontal and parietal lobes.9,10 Families characterized by the presence of mutations in MAPT provide the ideal construct to identify preclinical disease changes. Case studies assessing imaging in asymptomatic MAPT carriers show

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“…In more advanced stages of bvFTD, the loss of frontal and temporal neurons becomes more severe with greater deep layer involvement as the disease spreads throughout the white matter to more posterior regions and the subcortex (42). Moreover, presynaptic proteins such as α-synuclein and neurofilament proteins would be lost during severe cases of bvFTD; these two proteins are relatively preserved in a number of mild cases of bvFTD (43).…”

Section: Mild (N=20)mentioning

confidence: 99%

Efficacy of memantine on neuropsychiatric symptoms associated with the severity of behavioral variant frontotemporal dementia: A six-month, open-label, self-controlled clinical trial

Pan

Quan

Zhou

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Previous studies have focused on the curative effects of memantine in patients with mild-to-moderate frontotemporal lobar degeneration (FTLD); however, its benefits in patients with moderate-to-severe FTLD have not been investigated. The present study explores the behavioral, cognitive and functional effects of memantine on behavioral variant frontotemporal dementia (bvFTD) in patients with mild and moderate-to-severe stage bvFTD. A total of 42 patients with bvFTD completed a 6-month treatment plan of 20 mg memantine daily in an open-label, self-controlled clinical trial. Patients were divided into two groups according to their Mini-Mental State Examination (MMSE) score: Mild (score, 21-26); and moderate-to-severe (score, 4-20). Primary endpoints included Neuropsychiatric Inventory Questionnaire (NPI-Q) and Clinic Dementia Rating (CDR) scores, and secondary endpoints comprised Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D), MMSE, Montreal Cognitive Assessment (MoCA), Activity of Daily Life (ADL) and Hamilton Depression Rating Scale (HAMD) scores. Memantine treatment had no effect on overall NPI-Q scores, with the exception of the agitation subdomain in all patients with bvFTD. However, patients with moderate-to-severe bvFTD exhibited a better performance than patients with mild bvFTD, demonstrated by improved NPI-Q total scores and subscales of agitation, depression, apathy and disinhibition. In the moderate-to-severe group, CDR and HAMD scores remained stable, but MMSE, MoCA and ADL scores were reduced after 6 months of treatment. Memantine was well-tolerated in patients. In conclusion, patients with moderate-to-severe bvFTD responded significantly better to memantine in comparison to patients with mild bvFTD with regard to their neuropsychiatric scores, while memantine did not present any cognitive or functional benefits in patients with mild bvFTD. A randomized, double-blind, placebo-controlled clinical trial with a larger number of patients is required to verify these promising results for patients with moderate-to-severe bvFTD.

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Distribution of brain atrophy in behavioral variant frontotemporal dementia

Cited by 77 publications

References 41 publications

Orbitofrontal Dysfunction Discriminates Behavioral Variant Frontotemporal Dementia from Alzheimer’s Disease

Orbitofrontal Dysfunction Discriminates Behavioral Variant Frontotemporal Dementia from Alzheimer’s Disease

Altered functional connectivity in asymptomatic MAPT subjects

Efficacy of memantine on neuropsychiatric symptoms associated with the severity of behavioral variant frontotemporal dementia: A six-month, open-label, self-controlled clinical trial

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