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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.

This is a clinicopathologic study of a prospective, clinic-based cohort of patients with frontotemporal dementia (FTD)/Pick complex, who were followed to autopsy. A total of 60 patients with the clinical syndromes of the behavioural variant of FTD (FTD-bv) (n = 32), primary progressive aphasia (PPA) (n = 22), corticobasal degeneration syndrome (CBDS) (n = 4) and progressive supranuclear palsy (PSP) (n = 2) at onset, referred to a cognitive neurology clinic who had subsequent post-mortem examination were included. The most common histological variety was motor neurone disease type inclusion (MNDI) (n = 18), followed by corticobasal degeneration (CBD) (n = 12), then Pick's disease (n = 6), dementia lacking distinctive histology (DLDH) (n = 6) and PSP (n = 3). Others fulfilled the histological criteria for Alzheimer's disease combined with glial pathology (n = 6), Alzheimer's disease only (n = 4), Lewy body variant (n = 2), prion disease (n = 1), vascular dementia (n = 1) and undetermined (n = 1). The most common first syndrome among the MNDI and DLDH (tau negative) pathologies was FTD-bv, but subsequently progressive aphasia (PA), occasionally CBDS and semantic dementia also developed. Tau positive histologies of CBD, PSP and Pick bodies were most frequently associated with PPA onset or CBDS/PSP, but behavioural symptoms were also common. Age of onset was earlier in tau negative cases, but the duration of illness and gender distribution were about the same in all histological variants. Although the tau negative and positive histologies are predicted to some extent by the clinical onset, the extent of the overlap and the convergence of the syndromes in the course of the disease argue in favour of maintaining the clinical and pathological varieties under a single umbrella.

A referred cohort of 67 clinically defined PPA patients were compared to 99 AD patients with formal language and nonverbal cognitive tests in a case control design. Language fluency was determined at the first and last follow up visits. Quantitation of sulcal and ventricular atrophy on MRI was carried out in 46 PPA and 53 AD patients. Most PPA patients (57%) are relatively fluent when first examined. Visuospatial and memory functions are initially preserved. Aphemic, stuttering, “pure motor” presentation, or agrammatic aphasia are seen less frequently. Later most PPAs become logopenic and nonfluent, even those with semantic aphasia (dementia). In contrast, AD patients were more fluent and had relatively lower comprehension, but better overall language performance. MRI showed significant left sided atrophy in most PPA patients. Subsequent to PPA, 25 patients developed behavioral manifestations of frontotemporal dementia and 15 the corticobasal degeneration syndrome, indicating the substantial clinical overlap of these conditions. Language testing, particularly fluency scores supported by neuroimaging are helpful differentiating PPA from AD. The fluent–nonfluent dichotomy in PPA is mostly stage related. The aphemic-logopenic-agrammatic and semantic distinction is useful, but the outcomes converge. (JINS, 2003, 9, 710–719.)

Objective: To provide evidence for the hypothesis that the corticobasal degeneration syndrome (CBDs) overlaps significantly with primary progressive aphasia and frontotemporal dementia, and that CBDs is part of the Pick complex. Background: Corticobasal degeneration has been mainly described as a movement disorder, but cognitive impairment is also increasingly noted. Methods: Thirty-five cases of clinically diagnosed CBDs were followed-up with clinical, neuropsychological, and neuroimaging investigations. Twenty-nine patients were seen prospectively in movement disorder and cognitive neurology clinics; five of these came to autopsy. Six other autopsied cases that fulfilled the clinical criteria of CBDs were added with retrospective review of records. Results: All 15 patients presenting with movement disorders developed behavioral, cognitive, or language deficits shortly after onset or after several years. Patients presenting with cognitive problems (n = 20), progressive aphasia (n = 13), or frontotemporal dementia (n = 7) developed the movement disorder subsequently. Eleven cases with autopsy had CBD or other forms of the Pick complex. Conclusions: There is a clinical overlap between CBD, frontotemporal dementia, and primary progressive aphasia. There is also a pathologic overlap between these clinical syndromes. The recognition of this overlap will facilitate the diagnosis and avoid consideration of CBD as “heterogenous.”

A personality and behavioral disorder is an important and defining feature of frontal lobe dementia (FLD) or frontotemporal degeneration (FTD). The diagnosis usually depends on the progressive development of various behavioral symptoms rather than a set of neuropsychological measures. Quantification of the personality–behavior disorder is important for standardizing the diagnosis. An inventory was constructed to capture the major positive and negative behaviors and personality change, and it was administered prospectively to caregivers of 108 patients in a cognitive neurology clinic, at the time of first diagnostic assessment. The prevalence and extent of behavioral abnormality was quantitated in the clinic population of FLD, vascular dementia (VaD), Alzheimer's disease (AD), primary progressive aphasia (PPA), and depressive disorder (DD) patients. The mean scores of FLD patients were significantly above all other groups. Scores in VaD were also higher than in AD, PPA, and DD. Interrater reliability (Cohen's kappa of .90) and item consistency (a Cronbach alpha of .89) were both high. Perseveration, indifference, inattention, inappropriateness, and loss of insight rated highest in FLD, significantly different from all other groups. Apathy, aspontaneity, inflexibility, disorganization, impulsivity, personal neglect, and poor judgment were also significantly higher in FLD. Discriminant function correctly classified 92.7% versus all other patients (NON-FLD) in the study. A total of 18.8% of VaD patients were misclassified as FLD. Indifference, alien hand, and inappropriateness were the highest discriminant functions. Perseveration and verbal apraxia were important discriminatory items for FLD and PPA, respectively. The FBI is a standardized behavioral inventory useful to diagnose FLD, to differentiate it from other dementias, and to quantify the behavior disorder. (JINS, 2000, 6, 460–468.)

A substantive overlap between the clinical syndromes of frontal lobe dementia (FLD), frontotemporal dementia (FTD), or primary progressive aphasia (PPA), and corticobasal degeneration syndrome (CBDS) has been demonstrated in a population of 55 patients followed for more than 3 years in a cognitive neurology clinic. Patients presenting with the personality behavior disorder (FLD) often develop progressive aphasia (PA) and vice versa. CBDS is often associated with FLD and PA, and the extrapyramidal-apractic syndrome of CBDS often appears in FLD and PPA. The histopathological variations do not predict the clinical phenotype. The term Pick complex is suggested to indicate that these clinical and pathological variations are related and they were first described by Pick as clinical manifestations of fronotemporal atrophy. This term will avoid the confusion of using FLD or FTD or for the whole complex and also for the personality behavioral presentation. The relationship of the various clinical presentations has been strengthened by the discovery of chromosome 17 linkage in families manifesting them.

Objective:To utilize the diagnostic criteria of frontal lobe dementia (FLD).Methods:We studied 12 patients with FLD diagnosed clinically, with radiological confirmation in 10 and autopsy confirmation in 2; sixteen patients with Alzheimer's disease matched for stage and severity to FLD and 11 patients with depressive dementia were used as control groups. A 24-item Frontal Behavioral Inventory (FBI) using the most relevant behavioral manifestations of FLD was administered in these populations.Results:FLD patient scores on the FBI were much higher compared with control groups (AD and DD). Item analysis showed loss of insight, indifference, distractibility, personal neglect and apathy as the most frequent negative symptoms. Perseveration, disinhibition, inappropriateness, impulsivity, and irresponsibility were the most significant positive symptoms. An operational definition of FLD included a minimum FBI score of 27. Only one false positive was shown in the depressive group and none among the AD group, indicating little overlap between patient groups, and a high discriminating value of the FBI.Conclusions:The FBI appears to be a useful diagnostic instrument and a method to operate the behavioral criteria of FLD. Further prospective studies are warranted to establish validity.

The clock drawing test (CDT) is a widely used cognitive screening test. It is useful in identifying focal lesions and cognitive deficits in dementia groups. Lately, several studies attempted its use to differentiate between dementia subtypes. Although many studies have examined the CDT in dementia populations, research into the use of clock drawing in frontotemporal dementia (FTD) is limited. We examined quantitative (global) and qualitative (specific error type) differences on the CDT between FTD (n = 36) and Alzheimer's disease (AD; n = 25) patients and controls without dementia (n = 25). Results showed significantly lower overall scores in the dementia groups compared to the control group, whereas FTD patients scored significantly higher than the AD group. On qualitative analysis, the FTD group had fewer stimulus bound responses, conceptual deficits, and spatial or planning errors compared to the AD group. In conclusion, both global and error analysis of the CDT helped discriminate the FTD group from controls and AD patients. (JINS, 2006, 12, 159–165.)

To evaluate the construct validity of the Frontal Behavioral Inventory (FBI) and to describe the evolution of the behavioral abnormalities of the behavioral and aphasic presentations of frontotemporal dementia (FTD) by means of a 3-year longitudinal study.The FBI is a standardized behavioral questionnaire useful in the diagnosis and quantification of the personality and behavior disorder FTD.Patients who had three consecutive yearly assessments with the FBI were selected, 12 with the behavioral variant of FTD (FTD-bv) and 14 with Primary Progressive Aphasia (PPA).FBI scores rose as the disease progressed in both the FTD-bv and PPA groups over the 3 years of testing. Initial mean FBI scores of the FTD-bv group were above the cutoff for FTD as established for this diagnosis with previous standardization. By the third year, the mean FBI score of PPA patients was also above the established cutoff for FTD.The outcome of the study demonstrates that the FBI is sensitive to changes in behavior and personality in both variants of FTD. The FBI can be used to describe the evolution of symptoms and the course of the illness of Pick complex patients who present initially with FTD-bv or who present with PPA and subsequently develop the behavioral disorder.

Objective: To compare behavioral and cognitive testing in the clinical diagnosis of frontotemporal dementia (FTD). Methods: A clinically defined cohort of FTD (n = 52) is compared with 52 Alzheimer disease (AD) patients on a Frontal Behavioral Inventory (FBI) and cognitive tests (e.g., Mini-Mental State Examination, Mattis Dementia Rating Scale, Western Aphasia Battery, Wechsler Intelligence Scale, Wechsler Memory Scale). Fourteen patients with FTD had autopsy confirmation, and their tests are also compared with the rest of the FTD population. Results: The FTD and AD groups were matched in sex, duration, and severity of dementia. The total scores on the FBI showed the largest difference. Mini-Mental State Examination and Mattis Dementia Rating Scale total scores did not discriminate between the two groups. Memory subscores were lower in the AD group, and conceptualization and language-related scores were worse in the FTD group. Milder and earlier affected patients, who could carry on a large battery of neuropsychological tests, were much better distinguished by the FBI scores on discriminant function analysis. In contrast to 78% by the cognitive tests, 98% of the FTD and AD patients were differentiated by the FBI. Conclusions: Although memory scores were lower in AD and language scores in the FTD population, many of the cognitive tests do not distinguish between FTD and AD. On the other hand, a behavioral inventory is a useful adjunct in the diagnosis of FTD. Postmortem validation was carried out in a sizeable subset of the population, showing similar behavioral and cognitive data.

A 52-year-old right-handed woman who became deaf before the development of speech, suffered an occlusion of the right middle cerebral and a marked stenosis of the right anterior cerebral arteries. She showed no disturbance in the manual sign language or in finger-spelling, in contrast to previous reports of cases with left-sided damage.

Left- and right-handed normals of both sexes completed two visuospatial tasks along with a dichotic words test and a tachistoscopic dot enumeration test. The latter two tests yielded measures of verbal and nonverbal cerebral dominance, respectively. Contrary to earlier reports, not all left-handers were poorer than right-handers on spatial tasks. Such impairment was associated only with left-handers showing higher left-ear scores on the dichotic test (i.e. presumed right-hemisphere speech). Competition effects between verbal and nonverbal functions subserved by the same hemisphere, however, did not adequately account for these spatial deficits. Compared to males, females showed poorer spatial ability and a higher incidence of right-field superiority on the dot enumeration test, suggesting that left-hemisphere mediation of nonverbal ability may be disadvantageous.

A longitudinal case study of a patient with a progressive loss of meaning of objects with preserved phonology and syntax is presented. Repeated measures of language, praxis, visual cognition, and semantic processing were carried out. The patient still has preserved conversational speech, social skills, and orientation in her 8th year of her illness, but shows severe anomia and comprehension deficit in all modalities of stimulus presentation. In addition to standardized tests of language, cognition, and memory, specific experiments of categorization, modalities of word access, item consistency, category specificity, and definition of words were carried out. Results indicate a frequency dependent loss of meaning that was consistent in all modalities and throughout all object categories. However, the relative preservation of visual categorization of all categories tested and the language based categorization of animals suggested some fractionation of semantic memory. Relative preservation of autobiographical and personal memories versus semantic memory was a striking observation. Evidence for selective impairment of central semantic processing was obtained from experiments indicating item consistency of loss and the lack of semantic cuing. Neuroimaging evidence of left temporal lobe atrophy and the classical picture is compatible with similar cases published under the term semantic dementia or “transcortical sensory aphasia with visual agnosia” and suggest the diagnosis of Pick's disease. (JINS, 1998, 4, 388–398.)