A videotaped CIBIC for dementia patients: validity and reliability in a simulated clinical trial.

BACKGROUND: The global impression of a clinician is an Food and Drug Administration--mandated primary outcome measure for clinical trials in dementia. Reliability and validity of these measures are not well established. METHODS: A videotaped version of the Clinician's Interview Based Impression of Change (CIBIC) was evaluated. Raters were informed that the videotaped interviews were taken at baseline and 6 to 12 months later, when in fact half of the interviews were shown in reverse order. Ratings on "true order" interviews were compared with ratings on "reverse order" interviews. In addition, ratings by neurologists experienced in dementia were compared with those of less experienced raters. RESULTS: Inter-rater reliability of the neurologists was poor when measured by absolute agreement on a 7-point scale (kappa = 0.18). With a less stringent 3-point scale (better, worse, or unchanged), inter-rater reliability was significantly better for the true order videos (kappa = 0.51) than for the reversed order videos (kappa = 0.12). Validity also was reduced in the reverse order group: neurologists rated 90% of subjects correctly in the "true order" group and 63% correctly in the "reversed order" group. The inter-rater reliability of the neurologists was greater than the less experienced raters, but the validity of the neurologists' ratings was only marginally better. CONCLUSIONS: The reliability and validity of the videotape CIBIC are reasonable when patients follow the expected course of gradual decline, but are poor when patients appear to improve. These findings suggest that global assessments should be modified as outcome measures in clinical trials with patients with dementia.

The Frontal Lobe Score: part I: construction of a mental status of frontal systems.

OBJECTIVE: To develop a bedside mental status examination to assess the behavioural effects of damage to the frontal lobes. DESIGN: A prospective clinical comparison of patients with cerebral lesions of different locations. SUBJECTS: A total of 118 subjects were examined: 27 patients with cerebral lesions confined to the frontal lobes, 25 patients with cerebral lesions without involvement of the frontal lobes, 18 patients with mixed frontal/nonfrontal lesions, and 48 normal control subjects. MEASURES: Twenty-three mental status tests, clinical examinations and rating scales that had been reported as indicative of frontal lobe function were brought together. By statistical analysis, 12 tests and a neurobehavioural rating scale were selected. These constitute the Frontal Lobe Score (FLS). RESULTS: The FLS detected pure frontal lesions with a sensitivity of 77.7%. It discriminated patients with frontal lesions from normal control subjects with a specificity of 100%. Differentiation from patients with nonfrontal lesions was obtained with a specificity of 84%. CONCLUSION: The Frontal Lobe Score is a useful screening instrument for the clinical detection of effects of frontal lobe damage.

Autistic savants. [correction of artistic].

OBJECTIVE: The objectives of this study were to examine common patterns in the lives and artwork of five artistic savants previously described and to report on the clinical, neuropsychological, and neuroimaging findings from one newly diagnosed artistic savant. BACKGROUND: The artistic savant syndrome has been recognized for centuries, although its neuroanatomic basis remains a mystery. METHODS: The cardinal features, strengths, and weaknesses of the work of these six savants were analyzed and compared with those of children with autism in whom artistic talent was absent. An anatomic substrate for these behaviors was considered in the context of newly emerging theories related to paradoxical functional facilitation, visual thinking, and multiple intelligences. RESULTS: The artists had features of "pervasive developmental disorder," including impairment in social interaction and communication as well as restricted repetitive and stereotyped patterns of behavior, interest, and activities. All six demonstrated a strong preference for a single art medium and showed a restricted variation in artistic themes. None understood art theory. Some autistic features contributed to their success, including attention to visual detail, a tendency toward ritualistic compulsive repetition, the ability to focus on one topic at the expense of other interests, and intact memory and visuospatial skills. CONCLUSIONS: The artistic savant syndrome remains rare and mysterious in origin. Savants exhibit extraordinary visual talents along with profound linguistic and social impairment. The intense focus on and ability to remember visual detail contributes to the artistic product of the savant. The anatomic substrate for the savant syndrome may involve loss of function in the left temporal lobe with enhanced function of the posterior neocortex.

Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria.

OBJECTIVE: To improve clinical recognition and provide research diagnostic criteria for three clinical syndromes associated with frontotemporal lobar degeneration. METHODS: Consensus criteria for the three prototypic syndromes-frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia-were developed by members of an international workshop on frontotemporal lobar degeneration. These criteria build on earlier published clinical diagnostic guidelines for frontotemporal dementia produced by some of the workshop members. RESULTS: The consensus criteria specify core and supportive features for each of the three prototypic clinical syndromes and provide broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration. The criteria are presented in lists, and operational definitions for features are provided in the text. CONCLUSIONS: The criteria ought to provide the foundation for research work into the neuropsychology, neuropathology, genetics, molecular biology, and epidemiology of these important clinical disorders that account for a substantial proportion of cases of primary degenerative dementia occurring before the age of 65 years.

The temporal variant of frontotemporal dementia.

Frontotemporal dementia is a dementia syndrome with diverse clinical characteristics. Based upon clinical parameters and single photon emission computed tomography, we identified 47 frontotemporal dementia subjects. In 10 of these 47 the primary site of brain dysfunction was anterior temporal and orbital-frontal with other frontal regions relatively spared. In this temporal lobe variant (TLV) of frontotemporal dementia, five of the subjects had more severe left-sided, and five had more right-sided, hypoperfusion. The clinical, neuropsychological and neuropsychiatric features of predominantly left-sided (LTLV) and right-sided (RTLV) TLV subjects are discussed and contrasted with more frontal presentations of frontotemporal dementia. In LTLV, aphasia was usually the first and most severe clinical abnormality RTLV patients presented with behavioural disorders characterized by irritability, impulsiveness, bizarre alterations in dress, limited and fixed ideas, decreased facial expression and increased visual alertness. These findings suggest that: (i) frontotemporal dementia is clinically heterogeneous with bitemporal and inferior frontal lobe dysfunction contributing to the clinical presentation; (ii) behavioural disturbance and aphasia are the most prominent features of predominantly temporal subtypes of frontotemporal dementia; (iii) the right and left anterior temporal regions may mediate different behavioural functions. The results of this study suggests that TLV offers a valuable source of information concerning the behavioural disorders seen with combined anterior temporal and inferior frontal lobe dysfunction.

Ideomotor apraxia: behavioral dimensions and neuroanatomical basis.

Ideomotor apraxia, disordered movement execution to command, commonly follows left-hemisphere damage, implying left-hemisphere dominance for certain kinds of movements. To delineate this dominance we used different command modalities to elicit meaningful movements and tested imitation of nonsense movements. Twenty-seven patients with unilateral hemispheric stroke and 10 age-matched controls were evaluated. Patients with left-hemisphere damage performed both meaningful and nonsense movements poorer than the other study groups; thus, the meaningfulness of the movements is irrelevant for the left-hemisphere motor dominance. The performance varied, however, with the command modality and movement type. Based on this and earlier studies we posit that the left-hemisphere motor dominance is determined by the artificiality of the test situation (it concerns movements performed to command and out of the natural context) and increased spatial and temporal complexity of the demanded movements. No association between the lesion locus within the left hemisphere and the severity of the ideomotor apraxia was found.

Behavioral phenomenology in Alzheimer's disease, frontotemporal dementia, and late-life depression: a retrospective analysis.

Often patients in the early stages of Alzheimer's disease (AD), frontotemporal dementia (FTD), and late-life depression can be difficult to differentiate clinically. Although subtle cognitive distinctions exist between these disorders, noncognitive behavioral phenomenology may provide additional discriminating power. In 19 subjects with AD, 19 with FTD, 16 with late-life psychotic depression (LLPD), and 19 with late-life nonpsychotic depression (LLNPD), noncognitive behavioral symptoms were quantified retrospectively using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and compared using both a one-way ANOVA and a multivariate stepwise discriminant analysis, which utilized a jackknife procedure. The FTD group showed the highest mean total SCAN score, while the AD group showed the lowest. ANOVA showed significant differences in the mean total SCAN scores between the four diagnostic groups (P < .0001). With the discriminant analysis, the four disorders demonstrated different clusters of behavioral abnormalities and were differentiated by these symptoms (P < .0001). A subset of 14 SCAN item group symptoms was identified that collectively classified the following percentages of subjects in each diagnostic category: AD 94.7%, FTD 100%, LLPD 87.5%, and LLNPD 100%. These results indicate that AD, FTD, LLPD, and LLNPD were distinguished retrospectively by the SCAN without using cognitive data. Better definition of the longitudinal course of noncognitive behavioral symptoms in different dementias and psychiatric disorders will be valuable both for diagnosis and to help define behavioral syndromes that are associated with selective neuroanatomic and neurochemical brain pathology.

Aggressive, socially disruptive and antisocial behaviour associated with fronto-temporal dementia.

BACKGROUND: Research suggests an association between frontal and temporal injury and antisocial conduct. We studied the frequency of antisocial behaviours in fronto-temporal dementia (FTD) where pathology is anterior frontal-temporal, compared with Alzheimer's disease (AD) where pathology is primarily posterior temporal-parietal. METHOD: The presence of antisocial conduct was compared in 22 FTD versus 22 AD subjects. All FTD patients had anterior frontal or temporal hypoperfusion with single photon emission computed tomography, whereas those with AD had posterior temporal-parietal hypoperfusion. RESULTS: Ten FTD and one AD subject showed antisocial behaviours, which included assault, indecent exposure, shoplifting and hit-and-run driving. Three FTD subjects were arrested. This difference was highly significant (P = 0.004). CONCLUSIONS: Degeneration of frontal and temporal lobes predisposes to antisocial behaviour. This study supports a relationship between frontal-temporal dysfunction and certain types of antisocial activities.

Dementia with Lewy bodies: reliability and validity of clinical and pathologic criteria.

Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study. Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimer's disease (AD) (n = 18), Parkinson's disease (PD) (n = 5), or progressive supranuclear palsy (PSP) (n = 1) were studied. Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250 x magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of > 6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivity/specificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs (chi 2 = 5.48, p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement.

Familial Creutzfeldt-Jakob disease with a five-repeat octapeptide insert mutation.

We report a familial form of Creutzfeldt-Jakob disease, associated with a unique insert mutation of the PRNP gene in an American family of Ukrainian origin. Ten family members exhibited early age at onset and long-duration illnesses characterized primarily by personality changes, cognitive impairment, and spasticity. The proband, presenting at age 42 years, exhibited a fairly stable, nonprogressive course over 7 years, followed by precipitous decline and death in the eighth year. Other affected family members exhibited marked clinical heterogeneity. Each tested affected member had an insert mutation consisting of five extra octapeptide repeats between codons 51 and 91 of the PRNP gene on chromosome 20. Examination of two autopsy cases showed classic spongiform change, neuronal loss and astrocytosis in one case, and minimal pathologic abnormality in the other case. This report documents a new insert mutation of the PRNP gene, and confirms the early age of onset, characteristically prolonged clinical course, and clinical and pathologic heterogeneity seen in such mutations.

Neural basis of confabulation.

We present a case of acute alcohol-induced Korsakoff amnesia. A severe amnestic-confabulatory syndrome characterized the early clinical status. The initial neuropsychological tests demonstrated severe learning deficits plus impaired performance on many, but not all, tests of frontal lobe function. Single-photon emission CT (SPECT) at this stage showed hypoperfusion in the orbital and medical frontal regions and the medial diencephalic area. Four months later, the patient's amnesia remained but there was no confabulation. Repeat neuropsychological tests confirmed an ongoing severe amnesia, but performance on the frontal lobe tests now was normal. Repeat SPECT showed a return to normal perfusion in the frontal brain areas but little improvement in the medial diencephalic region. These findings along with data from the clinical literature suggest that confabulation results from dysfunction of orbital and a medial frontal cortex.

Visual agnosia and optic aphasia: are they anatomically distinct?

A patient with left infero-medial occipital-temporal infarct suffered a visual agnosia that, by a minor change of the task, could be manipulated to optic aphasia. Tools in actual use and pantomimes of tool use were better named than stationary tools, a dissociation that suggests differences in the ability of stimuli to evoke associations over multiple modalities. Based on this case and analysis of previous reports we suggest that optic aphasia differs from visual agnosia primarily in the degree of callosal disconnection and that the preserved demonstration of tools use and semantic classification of optic aphasia reflect right hemisphere contribution to visual processing.

Non-verbal environmental sound recognition after unilateral hemispheric stroke.

Recognition of non-verbal environmental sounds was investigated in 52 subjects with unilateral cerebro-vascular accidents and 18 age-matched normal controls. Impaired performance was most consistently found following cortical damage of homologous areas in either the left or the right hemisphere. Lesions involved the superior temporal gyrus (including the planum temporale), the inferior parietal lobe and the parietal operculum; this area appears to constitute the human auditory cortical processing area. We found different error patterns dependent upon the side of the lesion: patients with right hemisphere damage failed to discriminate between acoustically related sounds, patients with left hemisphere lesions tended to confuse semantically related sound sources. The impairment following right hemisphere damage was specific for non-verbal environmental sounds while left hemisphere damage was associated with disturbed semantic capabilities in multiple modalities.

Posterior cortical atrophy. Neuropathologic correlations.

OBJECTIVE: A subgroup of patients with progressive dementia has been reported with a marked predominance of symptoms attributed to the dysfunction of the posterior parieto-occipital cortex. These cases have been referred to as posterior cortical atrophy. The objective of this study was to determine whether posterior cortical atrophy is associated with distinct, uniform neuropathologic findings. DESIGN: Three individuals with progressive dementia that began with higher visual dysfunction (posterior cortical atrophy) were followed up to definitive neuropathologic diagnosis. RESULTS: Three separate neuropathologic entities were discovered: subcortical gliosis, Alzheimer's disease, and Creutzfeldt-Jakob disease. CONCLUSION: Posterior cortical atrophy is a clinically homogeneous but pathologically heterogeneous syndrome.

Progressive frontal dysfunction.

A number of causes of progressive mental impairment show a preponderance of frontal lobe symptoms. It is proposed that these disorders can be subdivided into primary and secondary frontal dementias, based on the symptomatology and the site of major pathological disruption. An anatomical explanation, based on variations in cortical and subcortical influences, aids in understanding the clinical differences.