Frontal Behavioral Inventory Research Articles

Cognitive Impairment in Neuro-Behcet's Disease and Multiple Sclerosis: A Comparative Study

Both multiple sclerosis (MS) and neuro-Behcet's disease (NBD) can cause a cognitive dysfunction mainly involving the executive functions. We conducted this study to clarify the probable differential cognitive/behavioral profiles of MS and NBD. Twenty consecutive cases with parenchymal NBD (13 male, seven female), and 20 cases with MS (five male, 15 female) were evaluated. Both groups had a thorough neurological examination; an evaluation for Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Beck's Depression Scale; and a detailed neuropsychological evaluation masked to the diagnosis. Among the two groups, male/female ratio differed significantly while other demographic and clinical features were not different. In California Verbal Learning Test, both short- and long-term delayed recall and cued recognition were worse in neuro-Behcet's cases. They had impaired semantic clustering and increased false positives. Stroop Test was also more impaired in neuro-Behcet's cases. They needed significantly more trials to complete the first category of the Wisconsin Card Sorting Test and had a poorer total Frontal Behavioral Inventory Score. Our results suggest that neuro-Behcet's patients have a more severe “frontal”-executive dysfunction than MS patients.

Fluorodeoxyglucose positron emission tomography in semantic dementia after 6 months of memantine: an open‐label pilot study

To follow up on the increases we reported in normalized metabolic activity in salience network hubs from a 2-month open-label study of memantine in frontotemporal dementia (FTD). We repeated fluorodeoxyglucose positron emission tomography (FDG-PET) after 6 months of drug use and subjected the data to Statistical Parametrical Mapping (SPM) analysis to reveal clusters of significant change from baseline. We also sought correlations between changes in behavioral disturbances on the Frontal Behavioral Inventory (FBI) and the PET signal. Recruitment of one progressive nonfluent aphasia and one behavioral variant FTD precluded statistical analysis for any FTD subtype other than semantic dementia (SD). The baseline-to-6-month interval showed increased normalized metabolic activity in the left orbitofrontal cortex (p < 0.002) for five participants with SD. The 2-6-month interval revealed a late increase in normalized metabolic activity in the left insula (p < 0.013), right insula (p < 0.009), and left anterior cingulate (p < 0.005). The right anterior cingulate showed both an initial increase and a delayed further increase (2-6 months, p < 0.016). FBI scores worsened by 43.3%. One participant with SD opted not to continue memantine beyond 2 months yet showed similar FDG-PET increases. Increases in normalized cortical metabolic activity in salience network hubs were sustained in SD over a 6-month period. Because one participant without medication also showed these changes, further investigation is recommended through a double-blind, placebo-controlled study with FDG-PET as an outcome measure.

Frontotemporal Dementia Behavioral Variant: Which Factors Underly Caregiver Strain? (P04.225)

Objective: We intended to find out whether severity of dementia, the frontal dysexecutive syndrome, parkinsonian motor symptoms, impaired instrumental activities of daily living (IADL), deficits in the Barthel index or behavioral and neuropsychiatric abnormalities contribute to caregiver strain in frontotemporal dementia behavioral variant (FTDbv). Background FTDbv is characterised by dementia, neuropsychiatric and behavioral abnormalities, sometimes parkinsonian motor symptoms, impaired IADL, and may be associated with substantial caregiver strain. Design/Methods: Consecutive patients with FTDbv and Alzheimer dementia (AD) were evaluated for cognition (CERAD+; frontal assessment battery, FAB, Dubois 2000), IADL (LawtonB Rivermead, Whiting 1980), Barthel Index, parkinsonian motor symptoms (Unified Parkinson Disease Rating Scale, UPDRS) and behavioral abnormalities (Neuropsychiatric inventory, NPI, Cummings 1994; Frontal Behavioral Inventory, FBI, Kertesz 2000). Results: Thirty-three patients with early FTDbv (Neary 1998) and 29 with probable AD (McKhann 1984) were examined. MMSE was similar in both groups (median 22). Age was higher in the AD group (mean 66 versus 75, p Conclusions: Preliminary data of our series confirms previous studies that caregiver strain is more severe in FTDbv than in AD. Behavioral abnormalities, assessed by NPI and FBI, but not severity of dementia or frontal dysexecutive impairment, parkinsonian motor symptoms, impairment in ADL or depression correlate with caregiver strain. FBI and NPI, informant based inventories, correlated to one another and revealed neuropsychiatric symptoms which probably contribute to caregiver strain in FTDbv. Supported by: Jubilaumsfonds of the Austrian National Bank Project number 13240. Disclosure: Dr. Ransmayr has received personal compensation for activities with Abbot, Allergan, Biogen-Idec, Boehringer-Ingelheim, Cephalon, Esai, GSK, Lundbeck, Merck-Serono, Merz, Novartis, The Austrian Neurological Society, The Austrian Parkinson Society, Austrial Alzheimer Society, BAIL, Sanofi-Aventis and UCB as a consultant, speaker, and board member.Dr. Ransmayr has received research support from Abbot, BIAL, Biogen-Idec, Lundbeck, Novartis, Sanofi-Aventis. Dr. Steffelbauer has nothing to disclose. Dr. Schmidegg has nothing to disclose. Dr. Struhal has nothing to disclose.

Neurobehavioral Dysfunction in Patients with Subcortical Vascular Mild Cognitive Impairment and Subcortical Vascular Dementia

Amnestic mild cognitive impairment (MCI) is considered to be a prodromal stage of Alzheimer's disease. Likewise, subcortical vascular MCI (svMCI) is considered as a prodromal stage of subcortical vascular dementia (SVaD). The objective of this study was to investigate neuropsychiatric features in patients with svMCI compared to healthy controls and patients with SVaD. We evaluated 31 patients with svMCI, 42 with SVaD, and 28 healthy controls who underwent neuropsychiatric assessments using the Neuropsychiatric Inventory (NPI) and the Frontal Behavioral Inventory (FBI). On both the NPI and FBI, SVaD patients had the most severe neuropsychiatric symptoms, followed by svMCI patients and then healthy controls, suggesting that svMCI might be a prodromal stage of SVaD in terms of neuropsychiatric abnormalities. When we compared the differences of mean scores between negative and positive symptoms in FBI, negative symptoms tended to be more predominant than positive symptoms in both svMCI and SVaD patients, but the tendency was stronger in SVaD patients than in svMCI patients. These results suggest that vascular cognitive impairment with small vessel disease would start with both negative and positive neuropsychiatric symptoms and progress to present more severe negative symptoms. These behavioral ratings may be useful for early detection of vascular cognitive impairment associated with small vessel disease.

Neuropsychological correlates of theory of mind in patients with early Parkinson's disease

The theory of mind is the ability to attribute mental states to oneself and others and to understand that others have beliefs, desires and intentions different from one's own. The aim of the study was to explore the neuropsychological correlates of theory of mind in patients affected by early Parkinson's disease (PD). Thirty-three PD patients and 33 age-, sex-, and education-matched control subjects underwent the Frontal Assessment Battery, as well as tasks assessing "cognitive" and "affective" theory of mind, and memory abilities; questionnaires evaluating behavioral disorders and quality of life were also administrated. Although the 2 groups did not differ on neuropsychological tasks, PD patients' performance on tasks assessing cognitive and affective theory of mind was significantly worse than controls. Moreover, PD patients had more behavioral disorders and worse quality of life than controls. After covarying for behavioral and quality of life scores, the differences between patients and controls on theory of mind tasks remained significant. "Cognitive" theory of mind was associated with Frontal Assessment Battery score and 2 domains of quality of life scale, whereas "affective" theory of mind scores correlated only with behavioral scales such as the Frontal Behavioral Inventory and Apathy Evaluation Scale. The results demonstrate that both affective and cognitive aspects of theory of mind are simultaneously impaired in early PD and suggest that deficits in the 2 subcomponents of theory of mind may be linked to dysfunction of different frontosubcortical circuitries in early PD.

Extrapyramidal Syndromes in Frontotemporal Degeneration

Descriptions of extrapyramidal (EP) involvement in Pick's disease (renamed recently as FTD) appeared 80 years ago. CBD pathology was confirmed as a common substrate for primary progressive aphasia (PPA). We suggested that CBD and PPA should be included with frontal lobe dementia as Pick complex. PSP was prototype for "subcortical dementia", and aphasia and apraxia, considered unusual for PSP, are now seen as a rule. The overlap of PSP and CBD is considerable. We recently reviewed our cohort with EPS in FTD and identified 22 patients with the movement disorder as a first syndrome and another larger group of 48 patients who developed EPS after an initial onset with a cognitive disorder: aphasic, behavioral or both. All cognitive onset CBD/PSP patients and all but two with motor onset developed aphasia during the course of their illness. General cognitive and behavioral measures are similar for each presentation, but language scores are worse in cognitive onset cases, reflecting the frequency of aphasic presentations. Anomic patients become non-fluent, logopenic, agrammatic and mute. Using the Frontal Behavioral Inventory (FBI), a questionnaire specifically designed for the spectrum of apathy and disinhibition displayed by patients with FTD, we have documented the behavior change in CBD/PSP with motor and cognitive onsets. The significant personality changes consisted of apathy, disinhibition, perseveration and inattention, some of the core symptoms of FTD. In 18 autopsied cases, 15 had tau pathology. The overlap of CBD/PSP with PPA and bvFTD suggests a spectrum of related entities and predicts tau-positive pathology. Cross-sectional studies without significant follow-up may not observe the subsequent development language or behavior deficit, or the evolution from PPA and/or FTD-bv to CBD/PSP.

Clinical Correlates of White Matter Tract Degeneration in Progressive Supranuclear Palsy

To use diffusion tensor imaging to assess white matter tract degeneration in progressive supranuclear palsy (PSP) and to investigate correlates between tract integrity and clinical measures. Case-control study. Tertiary care medical center. Twenty patients with probable PSP and 20 age- and sex-matched healthy controls were enrolled. All patients with PSP underwent standardized clinical testing, including the Frontal Behavioral Inventory and Frontal Assessment Battery to assess behavioral change, the PSP Rating Scale to measure disease severity, the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (parts II and III) to measure motor function, and the PSP Saccadic Impairment Scale to measure eye movement abnormalities. Fractional anisotropy and mean diffusivity were measured using region of interest analysis and tract-based spatial statistics. Compared with controls, abnormal diffusivity was observed predominantly in the superior cerebellar peduncles, body of the corpus callosum, inferior longitudinal fasciculus, and superior longitudinal fasciculus in patients with PSP. Fractional anisotropy values in the superior cerebellar peduncles correlated with disease severity (r = -0.59, P = .006), inferior longitudinal fasciculus correlated with motor function (r = -0.51, P = .02), and superior longitudinal fasciculus correlated with severity of saccadic impairments (r = -0.45, P = .047). The results of this study demonstrate that PSP is associated with degeneration of the brainstem, association, and commissural fibers and that this degeneration likely plays an important role in clinical dysfunction.

Gray matter correlates of behavioral severity in progressive supranuclear palsy

Behavioral changes occur in progressive supranuclear palsy. This study aimed to identify the anatomic correlate of behavioral severity in progressive supranuclear palsy. We performed standardized tests of behavioral severity (Frontal Behavioral Inventory), cognitive severity (Mini-Mental State Examination), motor severity (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III), and a 3.0-T volumetric head magnetic resonance imaging scan in 18 prospectively recruited subjects meeting National Institute of Neurological Diseases and Stroke-Society of Progressive Supranuclear Palsy criteria for probable progressive supranuclear palsy. Atlas-based parcellation was utilized to obtain regional gray matter volumes of frontal, temporal, and parietal lobe, and caudate and putamen, and voxel-based morphometry was used to assess voxel-level gray matter loss. We performed correlation analyses between total Frontal Behavioral Inventory score and gray matter volume, as well as assessed gray matter volume across three groups defined according to behavioral severity (mild, moderate, and severe) based on total Frontal Behavioral Inventory score. Specific behaviors, with the exception of apathy that occurred in 83% of the subjects, were relatively infrequent. There was no association between Frontal Behavioral Inventory and cognitive or motor severity. Regions of the frontal lobe, particularly, the lateral posterior frontal cortex, significantly correlated with the total Frontal Behavioral Inventory score when using both regional volume and voxel-level analyses. The groupwise analyses also supported these findings. The presence of apathy correlated with atrophy of the putamen. Behavioral severity in progressive supranuclear palsy appears to be associated with volume loss of frontostriatal regions, in particular, lateral posterior frontal lobe and putamen.

Differential diagnosis of behavioral variant of fronto-temporal dementia (bvFTD)

SummaryBackgroundThe aim of the paper is the differential diagnosis of various types of Fronto-Temporal Dementia (FTD), with the focus on its behavioural variant (bvFTD).Material/MethodMaterial and Method. Screening was done in order to assess the depth of dementia with the short version of MMSE, while evaluation of various variants of FTD was performed with the use of such neuropsychological tests as Newcomb and Chicago Fluency Tests, Wechsler Memory Scale - III (WMS-III), Western Aphasia Battery (WAB-R), and the Boston Naming Test (BNT). Behaviour was evaluated with a Polish version of the Frontal Behavioral Inventory (FBInv). The inventory consists of 24 questions which enable an evaluation of social behaviour disorders. The study included 112 patients - 68 men and 46 women treated in the Reintegrative -Training Centre of the Foundation for Persons with Brain Dysfunctions in Kraków and in the Clinic for Developmental Psychiatry, Psychotic Disorders and Old Age Psychiatry, of the Medical University at Gdańsk, who were suffering from various types of dementia.ResultsIt was found that FTD patients scored the highest, while the VAD patients scored somewhat lower in the FBInv. At the same time the scores obtained by PPA patients were higher in comparison to the control groups, but not as high as in the case of patients with FTD. In the process of the neurotherapy of FTD patients we found a reduction of the behavioral disturbances, despite the progression of the illness.ConclusionsThe results obtained in the present study confirmed the diagnostic value of FBInv in the differential diagnosis of various types of FTD and in the evaluation of neurotherapy efficacy.

Differentiating the frontal variant of Alzheimer's disease

Individuals with a clinical diagnosis of Alzheimer's disease (AD) may have prominent features of executive dysfunction and language impairment as well as behavioral abnormalities early in the disease ('high frontality'). When this occurs differentiation from frontotemporal dementia (FTD) is difficult. It is hypothesized that AD patients with high frontality may have clinical and pathological features that distinguish them from less frontal AD patients. In a well-characterized cohort of people with cognitive impairment, we used the Frontal Behavioral Inventory (FBI) in an attempt to identify AD patients with prominent frontal features (high-FBI AD) and distinguish them from the remainder of AD patients (low-FBI AD). The 18 high-FBI AD patients were compared with the 26 FTD patients who had an FBI performed and the 53 other low FBI AD patients. The individual FBI items did not differ significantly between the FTD and the high-FBI AD patients, and the high FBI AD patients were more like the FTD patients than the other AD patients with respect to presence of a family history of AD, proportion with homozygous apolipoprotein E(4) status, disability as measured by the Disability Assessment for Dementia (DAD) Scale and the Functional Rating Scale (FRS) and neuropsychiatric impairment as measured by the Neuropsychiatric Inventory (NPI). Memory symptom duration was similar in the high FBI AD group compared to the low FBI AD group. There is a subgroup of AD patients with high frontality that can be clinically distinguished from the remainder of AD patients but which requires pathological verification.

What Is Semantic Dementia?

To describe a large, clinically defined cohort of patients with semantic dementia (SD) that highlights important, sometimes overlooked features and to compare it with similar entities. Cohort study. A cognitive neurology clinic. A population of 48 patients clinically diagnosed with SD was contrasted with 52 patients with progressive nonfluent aphasia, 42 patients with a behavioral variety of frontotemporal dementia, and 105 patients with Alzheimer disease on speech output characteristics, comprehension, naming, and repetition subtests of the Western Aphasia Battery, the Frontal Behavioral Inventory, and other cognitive tests. Neuroimaging was visually analyzed, and 6 patients with SD had autopsy. Of 37 patients with probable SD, 48.6% had semantic jargon; 21.6%, excessive garrulous output; and 75.7%, some pragmatic disturbance. Semantic substitutions were frequent in SD (54.1%) but phonological errors were absent, in contrast to progressive nonfluent aphasia with the opposite pattern. All but 3 patients with probable SD questioned the meaning of words. Patients with SD had significantly lower naming and comprehension scores, and their fluency was between progressive nonfluent aphasia and Alzheimer disease or behavioral frontotemporal dementia. Behavior was abnormal in 94.6% of patients with probable SD. Semantic dementia is distinguishable from other presentations of frontotemporal dementia and Alzheimer disease, not only by fluent speech and impaired comprehension without loss of episodic memory, syntax, and phonology but also by empty, garrulous speech with thematic perseverations, semantic paraphasias, and poor category fluency. Questioning the meaning of words (eg, "What is steak?") is an important diagnostic clue not seen in other groups, and behavior change is prevalent.

Neurobehavioral differences between Alzheimer's disease and frontotemporal dementia: A meta-analysis

The differential diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) remains a difficult clinical issue. A recent meta-analysis by Hutchinson and Mathias (2007) found that many cognitive tests do not adequately differentiate between these types of dementia. However, their study did not examine the ability of neurobehavioral scales to distinguish between AD and FTD. The data from 33 studies, published between January 1994 and December 2008, examining the neurobehavioral symptoms of persons with AD (N = 2,305) and FTD (N = 971) were therefore analyzed. Weighted Cohen's d effect sizes, percentage overlap statistics, confidence intervals, and fail-safe Ns were calculated for each scale. The most discriminating measures were the Schedules for Clinical Assessment in Neuropsychiatry and the Scale for Emotional Blunting. The Middelheim Frontality Score and the Frontal Behavior Inventory also had excellent discriminative ability, surpassing the cognitive tests examined previously. Numerous other scales additionally showed large and significant differences between the AD and FTD groups, highlighting the importance of assessing neurobehavioral symptoms in this context. While these latter measures may be useful in providing a clinical profile of patients with dementia, greater overlap in the scores of patients with AD and FTD limits their usefulness in the context of differential diagnosis.

An Open-label Study of Memantine Treatment in 3 Subtypes of Frontotemporal Lobar Degeneration

There are currently no Food and Drug Administration-approved treatments for frontotemporal lobar degeneration (FTLD). The objectives of this study were to explore the tolerability of memantine treatment in FTLD and to monitor for possible effects on behavior, cognition, and function. Forty-three individuals who met clinical criteria for FTLD [21 with frontotemporal dementia (FTD), 13 with semantic dementia (SD), and 9 with progressive nonfluent aphasia (PA)] received 26 weeks of open-label treatment with memantine at a target dose of 20 mg daily. Concurrent treatment with acetylcholinesterase inhibitors was prohibited. Cognitive and functional outcome measures included the Mini Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog), clinical dementia rating-sum of boxes, Neuropsychiatric Inventory (NPI), Frontal Behavior Inventory, Executive Interview (EXIT25), Texas Functional Living Scale (TFLS), Geriatric Depression Scale, and Unified Parkinson's Disease Rating Scale-motor scale. Most subjects were able to tolerate the target dose of memantine. A transient improvement was observed on the total NPI score primarily in the FTD group. Variable declines were observed on the ADAS-cog, EXIT25, Frontal Behavior Inventory, NPI, TFLS, and UPDRS scores. The FTD and SD groups declined on most of the cognitive and behavioral outcome measures, but remained stable on the UPDRS, whereas the progressive nonfluent aphasia group remained relatively stable on the ADAS-cog, NPI, and TFLS, but declined on the UPDRS. Memantine was well-tolerated in these subjects. Future placebo-controlled trials of memantine in FTLD are warranted and may have greater power to detect behavioral and cognitive effects if focused on the FTD and SD clinical syndromes.

Generalized and Symptom-Specific Insight in Behavioral Variant Frontotemporal Dementia and Primary Progressive Aphasia

Behavioral variant frontotemporal dementia (FTD) and primary progressive aphasia (PPA) are related dementias with different presenting symptoms but with increasing symptom overlap as they progress. Loss of insight is associated with early behavioral variant FTD, but not PPA. This study used the Frontal Behavioral Inventory to compare patient and caregiver concepts of symptom presence and severity. Patients with behavioral variant FTD were found to have worse insight overall than PPA patients. However, the PPA group showed reduced insight into behavioral symptoms, and the behavioral variant FTD groups had intact insight into some language symptoms. Theoretical and clinical implications are discussed.

Pattern of behavioral disturbances in corticobasal degeneration syndrome and progressive supranuclear palsy

A careful characterization of behavioral abnormalities in corticobasal degeneration syndrome (CBDS) and progressive supranuclear palsy (PSP) by reliable tools is still lacking. Literature data provided evidence of the usefulness of the Frontal Behavioral Inventory (FBI) to operationalize such disturbances, particularly in the frontotemporal lobar degeneration spectrum. The study aimed to evaluate the frequency and pattern of presentation of behavioral disturbances in a large sample of CBDS and PSP patients by FBI. Sixty-eight CBDS and 57 PSP patients entered the study and underwent a standardized clinical and neuropsychological battery, and a structural brain imaging study. Behavioral disturbances were carefully analyzed by FBI. FBI scores were relatively low in both groups, being 6.7 +/- 8.2 and 5.6 +/- 6.1 in CBDS and PSP, respectively. Comparison of the behavioral profile between CBDS and PSP patients showed significant differences in apathy were more frequent in the latter (57.9% vs. 33.8%, P = 0.007), and the presence of alien hand/apraxia more frequent in the former group 39.7% vs. 10.5%, P = 0.001). Apathy correlated neither with age nor with motor disturbances as measured by UPDRS-III. Overall, the most frequent behavioral abnormalities present in both groups (>25%) were aspontaneity and logopenia. Aphasia (27.9%) and irritability (35.3%) were more frequent in CBDS compared to PSP, even if not statistically different. The present study has provided measures of behavioral disturbances in a population of PSP and CBDS patients, and further confirms the usefulness of the FBI scale.

Quality of life and neurobehavioral changes in survivors of malignant middle cerebral artery infarction

Malignant middle cerebral artery (MMCA) infarction is associated with a mortality rate of 80% under conservative treatment. Decompressive hemicraniectomy (DH) reduces mortality and improves the functional outcome of surviving patients. The purpose of this study was to examine quality of life (QoL) and neurobehavioral deficits in patients with space-occupying infarctions of the right- or left-sided hemisphere at 6 months after stroke. The Sickness Impact Profile (SIP) was used to assess QoL in 19 out of 29 consecutive patients that underwent DH after a malignant MCA infarction (14 on the right and 5 on the left hemisphere). Behavioral changes were evaluated with the Frontal Behavioral Inventory and the Beck Depression Inventory. Patients and relatives were also asked if, knowing the present outcome, they would agree again, in retrospect, to a DH. Barthel Index >60 was seen in 37% of our patients. Functional outcome was related to age. We found a higher reduction in the SIP's physical domain than in the psychosocial domain. Depressive symptoms were present in 50% of the patients. We didn't find significant differences in QoL or functional outcome between patients with right or left-sided infarctions. The most frequent neurobehavioral symptoms were decreased speech output, apathy, reduced spontaneity and irritability. Most patients and their relatives would again give consent to hemicraniectomy. The results show that younger patients had a significantly better outcome. QoL seems to be acceptable in both left- and right-sided infarctions, and retrospective agreement to hemicraniectomy is high in both patients and their relatives.

Development of methodology for conducting clinical trials in frontotemporal lobar degeneration

To design clinical trials for the frontotemporal lobar degenerations (FTLD), knowledge about measurement of disease progression is needed to estimate power and enable the choice of optimal outcome measures. The aim here was to conduct a multicentre, 1 year replica of a clinical trial in patients with one of four FTLD syndromes, behavioural variant frontotemporal dementia (bvFTD), progressive nonfluent aphasia (PNFA), progressive logopenic aphasia (PLA) and semantic dementia (SMD). Patients with one of the four FTLD syndromes were recruited from five academic medical centres over a 2 year period. Standard operationalized diagnostic criteria were used. In addition to clinical inclusion and exclusion criteria, patients were required to exhibit focal frontal, temporal or insular brain atrophy or dysfunction by neuroimaging. Patients underwent neuropsychological, functional, behavioural, neurological and MR imaging assessment at baseline and approximately 12 months later. Potential outcome measures were examined for their rates of floor and ceiling values at baseline and end of study, their mean changes and variances. The neuropsychological tests were combined into two cognitive composites -- one for language functions and the other for executive functions. There were 107 patients who underwent baseline assessment and 78 who completed a follow-up assessment within 10-16 months. Two global measures, the FTLD-modified Clinical Dementia Rating (FTLD-modified CDR) and the Clinical Global Impression of Change (CGIC) demonstrated decline in the majority of patients. Several cognitive measures showed negligible floor or ceiling scores either at baseline or follow-up. Scores declined at follow-up in the majority of patients. The cognitive, executive and combined composites were shown to be sensitive to change across all FTLD syndromes. Patients improved at follow-up on the behavioural scales -- the Frontal Behavioural Inventory (22%) and the Neuropsychiatric Inventory (28%) -- suggesting that these instruments may not be ideal for clinical trial use. It was feasible to recruit FTLD patients in a simulated multi-centre trial. There are several candidate outcome measures -- including the FTLD-CDR and the cognitive composites -- that could be used in clinical trials across the spectrum of FTLD.

Behavioral and activities of daily living inventories in the diagnosis of frontotemporal lobar degeneration and Alzheimer's disease.

The differential diagnosis between frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD) is often challenging.ObjectivesTo verify the usefulness of behavioral and activities of daily living inventories in the differential diagnosis between FTLD and AD.MethodsCaregivers of 12 patients with FTLD (nine with frontotemporal dementia, two with semantic dementia and one with progressive non-fluent aphasia) and of 12 patients with probable AD were interviewed. The Brazilian version of the Frontal Behavioral Inventory (FBI) and Disability Assessment for Dementia (DAD ) were used.ResultsThe mean of the MMSE score was 12.4±10.7for patients with FTLD and 11.9±6.2for patients with AD (p=0.93). Mean scores on the DAD were 33.7±27.7in patients with FTLD and 55.6±29.7in patients with AD (p=0.06), while for the FBI they were 42.6±10.0for FTLD and 16.7±11.7for AD (p<0.01).ConclusionsIn this study, FBI was found to be a helpful tool for the differential diagnosis between FTLD and AD. Although the DAD was not useful in differential diagnosis in our sample we believe it to be important for measuring the severity of the disease through quantitative and qualitative assessment of functional deficits of the patients.

A 6‐month, open‐label study of memantine in patients with frontotemporal dementia

To evaluate safety and effects on cognition and behavior of memantine 20 mg/day in the treatment of patients with frontotemporal dementia (FTD). This was a single-center, 6-month, open, uncontrolled study. Sixteen outpatients with a diagnosis of FTD were enrolled. On the CIBIC plus 26 weeks after baseline four of the 16 patients were minimally improved, four were unchanged, seven were minimally worse and one patient was moderately worse. Neither the Neuropsychiatric Inventory nor the Frontal Behavioral Inventory demonstrated statistically significant differences in behavior between baseline and final visit. There was an increase in the total Alzheimer's Disease Assessment Scale score, reflecting a decline in cognitive performance. Executive functions as well as activities of daily living and extrapyramidal motor symptoms (EPMS) remained unchanged during the trial. The number of patients was small, so that the evidence given by statistical tests is limited. Thus, the present study can only show trends regarding drug effects. As memantine is well-tolerated, further randomized and controlled studies should be conducted to evaluate drug efficacy.

Galantamine in Frontotemporal Dementia and Primary Progressive Aphasia

Background/Aims: The treatment of frontotemporal dementia (FTD) has been mainly symptomatic. Small randomized or open-label case control studies of neurotransmitters have been inconclusive. We tried galantamine in the 2 most common varieties of FTD. Method: Thirty-six behavioral variety FTD and primary progressive aphasia (PPA) patients were treated in an open-label period of 18 weeks and a randomized, placebo-controlled phase for 8 weeks with galantamine. The primary efficacy measures were the Frontal Behavioral Inventory, the Aphasia Quotient of the Western Aphasia Battery, the Clinical Global Impression of Severity and the Clinical Global Impression of Improvement. Results: No significant differences in behavior or language were found for the total group. A treatment effect (p = 0.009), in a subgroup of subjects with PPA in the global severity score, in favor of galantamine was detected in the placebo-controlled withdrawal phase but was not considered significant after correction for multiple comparisons. The language scores for the treated PPA group also remained stable compared to the placebo group, which showed deterioration. Conclusion: Galantamine is not effective in the behavioral variety of FTD, but a trend of efficacy is shown in the aphasic subgroup, which may be clinically significant. Galantamine appeared safe in FTD/PPA.