Barney J. Casey

Clinicopathological correlates in frontotemporal dementia

The term frontotemporal dementia (FTD) encompasses a range of clinical syndromes that are believed not to map reliably onto the spectrum of recognized pathologies. This study reexamines the relationships between clinical and pathological subtypes of FTD in a large series from two centers (n = 61). Clinical subtypes defined were behavioral variant FTD (n = 26), language variants (semantic dementia, n = 9; and progressive nonfluent aphasia, n = 8), and motor variants (corticobasal degeneration, n = 9; and motor neuron disease, n = 9), although most cases presented with a combination of behavioral and language problems. Unexpectedly, some behavioral cases (n = 5) had marked amnesia at presentation. The pathological subtypes were those with tau‐immunopositive inclusions (with Pick bodies, n = 20; or without, n = 11), those with ubiquitin immunopositive inclusions (n = 16), and those lacking distinctive histology (n = 14). Behavioral symptoms and semantic dementia were associated with a range of pathologies. In contrast, other clinical phenotypes had relatively uniform underlying pathologies: motor neuron disease predicted ubiquitinated inclusions, parkinsonism and apraxia predicted corticobasal pathology, and nonfluent aphasia predicted Pick bodies. Therefore, the pathological substrate can be predicted in a significant proportion of FTD patients, which has important implications for studies targeting mechanistic treatments. Ann Neurol 2004

Health habits and risk of cognitive impairment and dementia in old age: a prospective study on the effects of exercise, smoking and alcohol consumption.

Previous research has yielded inconsistent results on the effects of exercise, smoking and alcohol use on cognitive impairment and dementia in old age. We analysed data from the Sydney Older Persons Study to see if these health habits were associated with cognitive functioning, dementia or Alzheimers disease. Health habits were assessed in Wave 1 of the study, when the subjects were aged 75 years or over. Three years later, the subjects were tested for cognitive functioning and clinically examined for dementia and Alzheimers disease. The analysis was restricted to the 327 subjects examined in Wave 2 who were non‐demented in Wave 1. There were few significant associations between health habits and cognitive performance and these were not found consistently across cognitive measures. No associations were found with dementia or Alzheimers disease. While these health habits do not affect risk for dementia and cognitive impairment in the very elderly, who are at highest risk for these disorders, we cannot discount a role at younger ages.

Semantic impairment with and without surface dyslexia: Implications for models of reading

The two best-developed computational models of reading aloud, the DRC model of Coltheart and colleagues and the connectionist attractor model of Plaut and colleagues, offer very different views about the degree to which semantic knowledge is involved in lexical processing, and hence make differing predictions about how semantic impairment (as seen, for example, in semantic dementia) will impact on lexical processing in clinical cases. Two cases meeting the criteria for semantic dementia, PC and EM, were given a battery of tests comprising comprehension tasks, a reading task, and a visual word recognition (lexical decision) task. All tasks used the same target words allowing cross-test and cross-patient comparisons. Both cases showed significant impairment of semantic memory, and word comprehension was found to be related to the word frequency of the target words. PC demonstrated poor reading of irregular words, with a surface dyslexic pattern of reading aloud, and he performed poorly on the visual lexical decision task. His ability to read irregular words was related to their frequency and to his ability to comprehend them. In contrast, his visual lexical decision performance was not reliably influenced by his comprehension of the same words or by their frequency. EM demonstrated essentially perfect reading aloud of irregular words and essentially perfect visual lexical decision, despite her severe semantic impairment. The pattern of performance shown by EM is consistent with the DRC model of reading, but inconsistent with the connectionist attractor model and with the view, associated with that model, that orthographic and phonological processes cannot remain intact when semantic representations are degraded.

Informant-based staging of dementia using the clinical dementia rating.

The staging of dementia is ideally based on both an examination of the patient and a history taken from an informant. However, in some circumstances, only an informant history is possible. The aim of this study was to assess the validity of the Clinical Dementia Rating (CDR) when the rating is based solely on informant data. The CDR was used in a study of 360 persons aged 78 or older who were participants in a community survey, the Sydney Older Persons Study. The CDR was completed in two ways: (1) a social scientist made the ratings based on an informant interview; and (2) a physician made the ratings after an examination of the subject. All CDRs were scored in the conventional way, as well as by the revised method proposed by Gelb and St. Laurent (Alzheimer Dis Assoc Disord 1993;4:202-11). The informant CDR showed moderate agreement with the clinician CDR, showing that it would be a valid substitute in situations in which the subject could not be examined. The revised scoring method was slightly easier to implement than the conventional method.

Clinical phenotypes in autopsy-confirmed Pick disease

Background: Neuropathology of frontotemporal lobar degeneration is variable and relationship between the pathology and the clinical presentation remains uncertain. Abnormal deposits of hyperphosphorylated and ubiquitinated tau protein are present in 30% of cases, which include the classic presentation of Pick disease with argyrophilic, intraneuronal inclusions known as Pick bodies. This study aimed to improve sensitivity of clinicopathologic relations in cases with neuropathologically confirmed Pick disease and to identify clinical symptoms and signs predictive of disease progression. Methods: This was a retrospective analysis of 21 cases with a pathologic diagnosis of Pick disease and sufficient clinical information to establish early presenting clinical features from 2 specialist centers, representing 70% of all cases of Pick disease identified between 1998 and 2007 in these centers. Results: At presentation, 13/21 cases (62%) were clinically diagnosed with behavioral variant frontotemporal dementia (bvFTD) and 8/21 (38%) with language variant frontotemporal dementia (lvFTD) including 2 with mixed syndromes. Patients with bvFTD died on average 5 years earlier than those with lvFTD (7 years vs 12 years after disease onset). Pathologically, fewer Pick bodies were present in the frontal and inferior temporal cortices of bvFTD than lvFTD cases. In contrast, both groups showed decreased neuronal density in the dentate gyrus with increasing disease duration. Conclusions: The pathologic course of the disease in FTLD cases with Pick bodies is not uniform and disease duration can be estimated based on early clinical features. These findings have relevance as treatment options, which are likely to be pathology specific, are developed.

Screening for Dementia Using an Informant Interview

The effectiveness of an informant interview as a screening and assessment instrument for dementia was evaluated in a community survey of 398 people aged 78 or over. Participants received a battery of neuropsychological tests and were diagnosed for dementia by Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV; American Psychiatric Association, 1994) criteria. Informants were independently interviewed about changes in everyday cognitive functioning over the previous five years. A factor analysis of the 31 items from the informant interview showed a large general factor. A long 31-item scale was constructed, as well as a short 12-item scale. The long scale had a sensitivity of 89% and a specificity of 89% for detecting dementia, while the short scale had a sensitivity of 83% and a specificity of 87%. Correlations with subtests of the neuropsychological battery ranged between .4 and .7. The informant scales were less affected by premorbid ability and education than was the Mini-Mental State Examination (MMSE).

A longitudinal study of chronic disease and depressive symptoms in a community sample of older people

Previous research on the association between illness and depression in older people has relied on self-reported diagnoses with their inherent limitations in scope and reliability. This longitudinal study examined the association between depressive symptoms and medically-diagnosed chronic physical and neurodegenerative diseases and disability in community-living older people. In 1992, a random sample of 299 people aged 75 years and older underwent a clinical interview and medical examination by a physician experienced in geriatric medicine. This was repeated in 1995. The examination included diagnoses of chronic active physical illness, a standardized neurological examination, an assessment of functional disability and an abbreviated neuropsychological assessment. Depressive symptoms were assessed by the Centre for Epidemiological Studies - Depression scale. Multivariate analyses of concurrent associations, longitudinal associations and the impact of incident disease showed very few independent connections...

Clinical Diagnosis and Disability Among Community Dwellers Aged 75 and Over: The Sydney Older Persons Study

Objectives: Disability is an important predictor of health and community service utilisation. Understanding its pathogenesis has implications for planning of future health services. The aim of our study was to examine the contribution of systemic, psychiatric and neurodegenerative diseases to disability in an “old‐old” population.