Peter W. Schofield

Cognitive function in nondemented older women who took estrogen after menopause

Investigations of the effects of estrogen replacement on cognitive function in healthy older women have yielded disparate results. We evaluated the relationship between a history of estrogen use and cognitive test performance in 727 women participating in a large community-based study. Participants were followed longitudinally for an average of 2.5 years. Estrogen use history was obtained at baseline. Standardized tests of memory, language, and abstract reasoning were administered at baseline and at follow-up. Results indicate that women who had used estrogen replacement scored significantly higher on cognitive testing at baseline than nonusers, and their performance on verbal memory improved slightly over time. The effect of estrogen on cognition was independent of age, education, ethnicity, and APOE genotype. Results suggest that estrogen replacement therapy may help to maintain cognitive function in nondemented postmenopausal women.

Alzheimer's disease after remote head injury: an incidence study.

OBJECTIVE: To evaluate a history of remote head injury as a risk factor for subsequent dementia due to Alzheimers disease. METHODS: 271 participants of a community based longitudinal study of aging in north Manhattan without evidence of significant cognitive impairment were interrogated for a history of head injury on two occasions at entry into the study. The examining physician sought a history of head injury with loss of conciousness. Independently, a risk factor interviewer inquired about a history of head injury with loss of consiousness or amnesia, the duration of any loss of consiousness, and the date of the head injury. Patients were followed up with standardised annual evaluations for up to five years to determine the first occurrence of dementia. RESULTS: Over the course of the study incident dementia due to probable or possible Alzheimers disease was diagnosed in 39 patients. Cox proportional hazards modelling showed that a history of head injury with loss of consiousness reported to the physician was associated with earlier onset of dementia due to Alzheimers disease (relative risk (RR) = 4.1, 95% confidence interval (95% CI) 1.3-12.7). head injury with loss of consiousness or amnesia reported to the risk factor interviewer was not significantly associated with earlier onset of Alzheimers disease overall (RR 2.0, 95% CI 0.7-6.2), but those who reported loss of consiousness exceeding five minutes were at significantly increased risk (RR 11.2, 95% CI 2.3-59.8). Incident Alzheimers disease was significantly associated with head injury which occurred within the preceding 30 years (RR 5.4, 95% CI 1.5-19.5). CONCLUSION: The results of this cohort study are consistent with the findings of several case-control studies suggesting that head injury may be a risk factor for Alzheimers disease.

An association between head circumference and Alzheimer's disease in a population-based study of aging and dementia

We investigated the association between head circumference (HC) and Alzheimers disease (AD) in a cross-sectional population-based study of aging in North Manhattan. Six hundred forty-nine subjects underwent neurologic, neuropsychological, and anthropometric evaluations; apolipoprotein E(apoE) genotype was available for a subsample of 300 individuals. Logistic regression analyses were performed with AD the outcome of interest to evaluate any association between HC and AD. In these analyses, HC evaluated as a continuous variable was associated with AD (OR 0.8, 95% CI 0.7-0.9) after adjusting for age, education, and ethnicity, gender, and height. Analyses suggested that increased risk resided mainly in those with smallest HC. Thus, women whose HC was within the lowest quintile of HC for women were 2.9 (95% CI 1.4-6.1) times more likely to have AD, after adjusting for age, education, and ethnicity; and men in the lowest quintile of HC (for men) were 2.3 times more likely to have AD (95% CI 0.6-9.8). There was no confounding by height, weight, or apoE genotype. The results are consistent with previous studies that suggest that premorbid brain size may influence the age-specific risk for AD. Future epidemiologic studies seeking environmental risk factors for AD may benefit by making HC measurements on all subjects to decrease the variance associated with other potential risk factors.

Cohort Profile: The Hunter Community Study

In almost every country, the proportion of people aged 460 years is growing faster than any other age group and is expected to reach 2 billion worldwide by 2050. Internationally and nationally, considerable efforts are being made to promote active ageing. However, Australia lacks the kind of comprehensive longitudinal research underway in Europe and North America. Although Australia does have a number of longitudinal studies designed to address various issues of health and ageing among older adults, only a few of these studies include a broad and comprehensive range of physical and biological measures. The Hunter Community Study (HCS) is a collaborative study between the University of Newcastle’s School of Medicine and Public Health and the Hunter New England Area Health Service. It is a multi disciplinary initiative that was established to fill some existing gaps in ageing research in Australia and is unique in that it has collected detailed information across all six key policy themes as identified in the Framework for an Australian Ageing Research Agenda. What does the study cover?

Cross-cultural neuropsychological assessment: a comparison of randomly selected, demographically matched cohorts of English- and Spanish-speaking older adults.

As the US population of elderly Hispanics continues to grow, there is an increasingly greater need for neuropsychological measures that are appropriate for assessing Spanish-speaking elders. The current study compared the performance of randomly selected, community-based samples of English- and Spanish-speaking elders on a brief neuropsychological test battery. Subject groups were matched for age and education. Multivariate analysis indicated significant group differences on the test battery. English and Spanish speakers scored comparably on many language-based tasks, but Spanish speakers scored significantly lower on almost all of the nonverbal measures. Significant group differences were observed on multiple-choice matching and recognition memory for stimuli from the Benton Visual Retention Test, as well as on Identities and Oddities from the Mattis Dementia Rating Scale, category fluency, and Complex Ideational Material from the Boston Diagnostic Aphasia Examination (BDAE). Results suggest that caution is warranted when using nonverbal as well as verbal measures to assess non-English-speaking individuals.

A preliminary study of apolipoprotein E genotype and psychiatric manifestations of Alzheimer's disease

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype.Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations. NEUROLOGY 1996;47: 256-259

Bilingualism does not alter cognitive decline or dementia risk among Spanish-speaking immigrants.

OBJECTIVE Clinic-based studies suggest that dementia is diagnosed at older ages in bilinguals compared with monolinguals. The current study sought to test this hypothesis in a large, prospective, community-based study of initially nondemented Hispanic immigrants living in a Spanish-speaking enclave of northern Manhattan. METHOD Participants included 1,067 participants in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were tested in Spanish and followed at 18-24 month intervals for up to 23 years. Spanish-English bilingualism was estimated via both self-report and an objective measure of English reading level. Multilevel models for change estimated the independent effects of bilingualism on cognitive decline in 4 domains: episodic memory, language, executive function, and speed. Over the course of the study, 282 participants developed dementia. Cox regression was used to estimate the independent effect of bilingualism on dementia conversion. Covariates included country of origin, gender, education, time spent in the United States, recruitment cohort, and age at enrollment. RESULTS Independent of the covariates, bilingualism was associated with better memory and executive function at baseline. However, bilingualism was not independently associated with rates of cognitive decline or dementia conversion. Results were similar whether bilingualism was measured via self-report or an objective test of reading level. CONCLUSIONS This study does not support a protective effect of bilingualism on age-related cognitive decline or the development of dementia. In this sample of Hispanic immigrants, bilingualism is related to higher initial scores on cognitive tests and higher educational attainment and may not represent a unique source of cognitive reserve.

Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus

Background: Most patients with pure nonprogressive congenital cerebellar ataxia have a sporadic form of unknown heredity and etiology. Several small families have been reported with a dominantly inherited nonprogressive congenital ataxia (NPCA). Methods: The authors ascertained and clinically characterized a four-generation pedigree segregating an autosomal dominant type of congenital nonprogressive cerebellar ataxia associated with cognitive impairment. Following the exclusion of several SCA localizations (SCA-1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 17, IOSCA, and DRPLA), a genome-wide linkage study was performed. Results: Examination of the family showed that all affected members had gait ataxia and cognitive disability with variable features of dysarthria, dysmetria, dysdiadochokinesia, nystagmus, dystonic movements, and cerebellar hypoplasia on imaging. Clinical signs of pyramidal tract dysfunction and sensory changes were absent. A genome-wide search in this family detected linkage to chromosome 3p with a maximum two-point lod score of 4.26 at D3S3630. This localization to the pter is distal to D3S1304, as defined by a recombination event. This overlaps with the SCA15 locus, with the critical overlapping region between the microsatellite markers, D3S1304 and D3S1620 (approximately 8 cM). Conclusion: Autosomal dominant congenital nonprogressive cerebellar ataxia with or without cerebellar hypoplasia overlaps with the SCA15 locus on chromosome 3pter.

Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxia.

BackgroundCongenital nonprogressive spinocerebellar ataxia is characterized by early gross motor delay, hypotonia, gait ataxia, mild dysarthria and dysmetria. The clinical presentation remains fairly stable and may be associated with cerebellar atrophy. To date, only a few families with autosomal dominant congenital nonprogressive spinocerebellar ataxia have been reported. Linkage to 3pter was demonstrated in one large Australian family and this locus was designated spinocerebellar ataxia type 29. The objective of this study is to describe an unreported Canadian family with autosomal dominant congenital nonprogressive spinocerebellar ataxia and to identify the underlying genetic causes in this family and the original Australian family.Methods and ResultsExome sequencing was performed for the Australian family, resulting in the identification of a heterozygous mutation in the ITPR1 gene. For the Canadian family, genotyping with microsatellite markers and Sanger sequencing of ITPR1 gene were performed; a heterozygous missense mutation in ITPR1 was identified.ConclusionsITPR1 encodes inositol 1,4,5-trisphosphate receptor, type 1, a ligand-gated ion channel that mediates calcium release from the endoplasmic reticulum. Deletions of ITPR1 are known to cause spinocerebellar ataxia type 15, a distinct and very slowly progressive form of cerebellar ataxia with onset in adulthood. Our study demonstrates for the first time that, in addition to spinocerebellar ataxia type 15, alteration of ITPR1 function can cause a distinct congenital nonprogressive ataxia; highlighting important clinical heterogeneity associated with the ITPR1 gene and a significant role of the ITPR1-related pathway in the development and maintenance of the normal functions of the cerebellum.

Traumatic brain injury among Australian prisoners: Rates, recurrence and sequelae

Primary objective: To establish the prevalence, severity, recurrence and sequelae of past traumatic brain injury (TBI) among individuals recently received into custody. Research design: Cross-sectional random sample of men recently received into the New South Wales’ (NSW) criminal justice system. Procedures: Participants were screened for a history of TBI including the injury setting, severity, treatment and sequelae of up to five separate TBI episodes. Outcomes and results: Of 200 study participants, 82% endorsed a history of at least one TBI of any severity and 65% a history of TBI with a loss of consciousness (LOC). Multiple past TBIs were common, as were ongoing sequelae. Treatment for the TBI was more common among those TBIs with a LOC compared with no LOC (66% vs. 39%). Conclusions: Among individuals entering the criminal justice system, past TBI is common and often associated with ongoing neuropsychiatric and social sequelae. Screening for TBI at the point of reception may be warranted to better understand and treat those with ongoing neuropsychiatric sequelae arising from the TBI.