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Objective: This study determined the influence of depressive symptoms on subsequent mortality of all causes. Method: The Honolulu Heart Program, established in 1965, is a prospective, community-based cohort of Japanese American men living in Hawaii. The analysis was based on 3,196 Japanese American men aged 71-93 at the time of the fourth examination in 1991-1993. Depressive symptoms were measured by use of an 11-question version of the Centers for Epidemiologic Studies Depression Scale questionnaire. All-cause mortality data were available for 6 years of follow up. Data were analyzed on the basis of presence or absence of chronic diseases. Results: The overall prevalence of frequent depressive symptoms was 9.9%. Age-adjusted mortality rates at 3 years were 48.0 and 30.3 per 1,000 person-years for the depressed and nondepressed groups, respectively. At 6 years, the rates were 54.1 (depressed) and 41.5 (nondepressed) per 1,000 person-years. After adjustment for age, marital status, and antidepressant use, the relative risk for all cause mortality associated with depressive symptoms was 1.53 for 3-year and 1.27 for 6-year mortality. Among participants who were healthy (without cognitive impairment, coronary heart disease, stroke, diabetes, or cancer), the association between depressive symptoms and mortality was greater (relative risk of 2.30 and 1.57 for 3 and 6-year mortality, respectively). Among participants with chronic disease, there were no significant associations between depressive symptoms and mortality. Conclusions: Depressive symptoms are a risk factor for mortality in elderly people, particularly in physically healthy individuals. (Am J Psychiatry 2002; 159:1127-1132)

Daytime sleepiness has been found to be associated with 3-year incident dementia and cognitive decline in Japanese-American men aged 71-93 in a study in Honolulu after adjusting for age and other factors. Insomnia was not associated with cognitive decline/dementia. In the study 2,346 men were screened negative for prevalent dementia at baseline, then screened in a 3-yr follow-up examination.

Research demonstrates an inverse correlation between childhood residence in Japan and cognitive test performance in late life among Japanese men. Data further reveal that for assessing the cognitive performance, use of the native language of the subjects yields better results.

Older Japanese-American men complain rarely of snoring and sleep apnea. Among a group of 2,905 older men, those few who reported sleep apnea symptoms tended to snore habitually and to be sleepy during the day. Snorers were often heavier without evidence of cardiovascular disease, stroke, dementia, or cognitive dysfunction. Self-reported sleep apnea was related only to a history of pneumonia.

Many elderly men with dementia stop driving, even in the early stages of the disease. This was the conclusion of researchers who surveyed 643 men aged 74 to 95. About 80% of the men without dementia still drove compared to 46% with very mild dementia, 22% with mild dementia and 4% with moderate to severe dementia.

Cognitive impairment and its severe form dementia are increasingly prevalent in older adults and loom as a public health disaster unless effective interventions are developed. Cognitive impairment is a convergent trait caused by damage from an idiosyncratic mix of four prevalent diseases (Alzheimer disease; vascular brain injury; Lewy body diseases, such as Parkinson disease and dementia with Lewy bodies; and limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy) that is counterbalanced by individually varying resilience, which is comprised of reserve and compensation. Brain regional damage from each of these four prevalent diseases is generated by the net effect of injury and (mal)adaptive response and is accompanied by characteristic lesions. Existing therapeutics enhance resilience, whereas most agents under development target mechanisms of damage with only suppression of vascular brain injury yet to show therapeutic promise. We hope to anticipate future tailored interventions that target mechanisms of damage and thereby avert the oncoming surge of cognitive impairment and dementia in older adults.

Cognitive functioning at 3 to 6 years before onset of dementia is analyzed in a sample of Japanese Americans, who were participating in Honolulu-Asia Aging study. Cognitive deficits and memory impairments symptoms were observed in subjects who later on developed dementia.

This study had two goals. First, we investigated how World War II (WW II) military service impacted marital stability during men's young and middle adulthood in a large community sample of American men of Japanese descent. Second, within a subgroup of WW II veterans, we assessed how the level of combat exposure affected marital stability.

Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience. There were significant differences in prevalence of Alzheimer disease neuropathologic change, small vessel vascular brain injury, and Lewy body disease between these 2 studies, suggesting that sex, ethnicity, and lifestyle factors may significantly influence resistance to developing brain injury with age. In contrast, hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive performance, suggesting that hippocampal sclerosis could act sequentially with other diseases to impair cognitive function. Strikingly, despite these observed differences, the proportion of individuals resistant to all 4 diseases of brain or displaying apparent cognitive resilience was virtually identical between HAAS and Nun Study participants. Future in vivo validation of these results awaits comprehensive biomarkers of these 4 brain diseases.

To determine the associations between classes of antihypertensive medication use and the risk of cognitive impairment among elderly hypertensive men.

To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD).

The Honolulu-Asia Aging Study (HAAS) is a longitudinal epidemiologic investigation of rates, risk factors, and neuropathologic abnormalities associated with cognitive decline and dementia in aged Japanese-American men. The project was established in 1991 and will be brought to closure in 2012. Age-specific rates of total dementia and the major specific types of dementia in HAAS participants are generally similar to those reported from other geographic, cultural, and ethnic populations. Risk factors for dementia in the HAAS include midlife hypertension and other factors previously shown to influence cardiovascular disease. The autopsy component of the project has yielded novel findings, the most illuminating of which is the demonstration of 5 important lesion types linked independently to cognitive impairment. While one of these – generalized atrophy – is strongly associated with both Alzheimer lesions and microinfarcts, it also occurs in the absence of these lesions and is independently correlated with dementia. Each lesion type is viewed as representing a distinct underlying pathogenic process. Their summed influences is an especially robust correlate of dementia in the months and years prior to death.

Oxidative stress and oxidized dopamine contribute to the degeneration of the nigrostriatal pathway in Parkinson's disease (PD). Selenoproteins are a family of proteins containing the element selenium in the form of the amino acid selenocysteine, and many of these proteins have antioxidant functions. We recently reported changes in expression of the selenoprotein, phospholipid hydroperoxide glutathione peroxidase GPX4 and its co-localization with neuromelanin in PD brain. To further understand the changes in GPX4 in PD, we examine here the expression of the selenium transport protein selenoprotein P (Sepp1) in postmortem Parkinson's brain tissue. Sepp1 in midbrain was expressed in neurons of the substantia nigra (SN), and expression was concentrated within the centers of Lewy bodies, the pathological hallmark of PD. As with GPX4, Sepp1 expression was significantly reduced in SN from PD subjects compared with controls, but increased relative to cell density. In putamen, Sepp1 was found in cell bodies and in dopaminergic axons and terminals, although levels of Sepp1 were not altered in PD subjects compared to controls. Expression levels of Sepp1 and GPX4 correlated strongly in the putamen of control subjects but not in the putamen of PD subjects. These findings indicate a role for Sepp1 in the nigrostriatal pathway, and suggest that local release of Sepp1 in striatum may be important for signaling and/or synthesis of other selenoproteins such as GPX4.

BACKGROUND Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease (LBD) are the major contributors to dementia in community- and population-based studies. OBJECTIVE To estimate the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults. DESIGN Autopsy study. SETTING Community- and population based. PARTICIPANTS A total of 1672 brain autopsies from the Adult Changes in Thought study, Honolulu-Asia Aging Study, Nun Study, and Oregon Brain Aging Study, of which 424 met the criteria for CN. MAIN OUTCOME MEASURES Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque density, Braak stage for neurofibrillary tangles, LB distribution, and number of cerebral microinfarcts. RESULTS Forty-seven percent of CN cases had moderate or frequent neuritic plaque density; of these, 6% also had Braak stage V or VI for neurofibrillary tangles. Fifteen percent of CN cases had medullary LBD; 8% also had nigral and 4% isocortical LBD. The presence of any cerebral microinfarcts was identified in 33% and of high-level cerebral microinfarcts in 10% of CN individuals. Overall, the burden of lesions in each individual and their comorbidity varied widely within each study but were similar across studies. CONCLUSIONS These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts.

The cognitive reserve hypothesis would predict that use of written Japanese should confer protection against dementia because of the complexity of its ideograms compared with written English. We sought to test this hypothesis in analyses from a longitudinal study of Japanese-American men.

BACKGROUND The relationship between total cholesterol levels and dementia is unclear. OBJECTIVE To compare the natural history of change in total cholesterol across 26 years between men who did and did not develop dementia 3 years after the last measurement. DESIGN, SETTING, AND PARTICIPANTS In the Honolulu-Asia Aging Study, 1027 Japanese American men had total cholesterol levels assayed on 5 occasions between 1965 and 1993 and were screened for dementia on 2 occasions between 1991 and 1996. MAIN OUTCOME MEASURE The slope of 26-year change in serum total cholesterol levels was estimated by a repeated-measures analysis and was compared between men with incident dementia (n = 56) and those without dementia (n = 971) at the end of the follow-up period. RESULTS Cholesterol levels in men with dementia and, in particular, those with Alzheimer disease had declined at least 15 years before the diagnosis and remained lower than cholesterol levels in men without dementia throughout that period. The difference in slopes was robust to adjustment for potential confounding factors, including vascular risk factors, weight change, alcohol intake, and use of lipid-lowering agents. CONCLUSION A decline in serum total cholesterol levels may be associated with early stages in the development of dementia.Arch Neurol. 2007;64:103-107 --

The efficacy of treating older persons for hypertension remains controversial. Although clinical trials suggest no short-term harm, or some benefits, there are little data on the effect on cognitive function of long-term antihypertensive treatment. We evaluated the risk of dementia and cognitive decline associated with duration of antihypertensive treatment.

The cornu ammonis 1 region of the hippocampus (CA1) sector of hippocampus is vulnerable to both Alzheimer's disease (AD)‐type neurofibrillary degeneration and anoxia–ischemia. The objective of this article is to compare number and size of neurons in CA1 in AD versus ischemic vascular dementia. Unbiased stereological methods were used to estimate the number and volume of neurons in 28 autopsy‐derived brain samples. For each case, the entire hippocampus from one cerebral hemisphere was sliced into 5mm slabs (5–7 slabs/case), cut into 50μm sections, and stained with gallocyanine. Using the optical dissector, we systematically sampled the number and size of neurons throughout the extent of CA1 and CA2. The total number of neurons was significantly less in AD compared with ischemic vascular dementia (p< 0.02), but there was no significant difference in neuron size. The greatest loss of neurons was observed in two cases with combined AD and hippocampal sclerosis. Regardless of causative diagnosis, the number of CA1 neurons correlates with magnetic resonance imaging–derived hippocampal volume (r= 0.72; p< 0.001) and memory score (r= 0.62; p< 0.01). We conclude that although CA1 neuron loss is more consistently observed in AD than ischemic vascular dementia, severity of loss shows the expected correlation with structure and function across causative subtype. Reductions in magnetic resonance imaging–derived hippocampal volume reflect loss, rather than shrinkage, of CA1 neurons. Ann Neurol 2005;57:896–903

Norms for cognitive measures used to assess dementia are scant for minority groups, in particular for older Japanese Americans. Using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychology Battery, we compared the baseline performance of demented and nondemented Japanese Americans. Participants came from two harmonized epidemiological studies of dementia which were examined separately: the Kame Project, Seattle (350 men and women; 201 nondemented), age 65 and older; Honolulu-Asia Aging Study (HAAS), Hawaii (418 men; 120 nondemented), age 71 and older. The measures examined were Verbal Fluency; abbreviated Boston Naming; constructional praxis; and Word List Learning, Recall, and Recognition. Within each study, the CERAD measures distinguished between nondemented participants and those with mild cognitive impairment. Among persons with dementia, average level of performance decreased as severity of dementia increased. Determinants of score (age, education, language of administration, stage of dementia) varied between the two studies. Among Japanese Americans, the CERAD Neuropsychology Battery distinguished nondemented persons from those with dementia, but was less consistent in distinguishing levels of severity of dementia. This battery is useful for comparative epidemiological studies of dementia in minority populations. (JINS, 2005, 11, 192–201.)

Neocortical neuritic plaques and neurofibrillary tangles are hallmark neuropathological lesions of dementia. Concomitant cerebrovascular lesions increase dementia severity in patients meeting neuropathological criteria for Alzheimer's disease and contribute to cognitive impairment in persons with mild entorhinal Alzheimer lesions. This study investigates whether individuals with sparse neocortical neuritic plaques experience increased odds of crossing the threshold to clinical dementia when they have coexistent cerebrovascular lesions. Dementia examinations were given to 3,734 men during the 1991–1993 Honolulu‐Asia Aging Study examination and to 2,603 men during the 1994–1996 examination. Lesion quantification was done without clinical data. Among 333 autopsied men, 120 had dementia, 115 had marginal results, and 98 had normal cognition. In men with neurofibrillary tangles, dementia frequency increased with increasing neuritic plaque density, and increased further in the presence of cerebrovascular lesions. The association was strongest in men with sparse neuritic plaques (1–3/mm2) where dementia frequency more than doubled with coexistent cerebrovascular lesions (45 vs 20%). Among all dementia cases, 24% were linked to cerebrovascular lesions. Findings suggest cerebrovascular lesions are associated with a marked excess of dementia in cases with low neuritic plaque frequency. Prevention of cerebrovascular lesions may be critically important in preserving late‐life cognitive function. Ann Neurol 2005

Substantia nigra (SN) neurons were counted on single, transverse caudal midbrain sections from 217 male participants in the Honolulu‐Asia Aging Study, aged 74–97 years at death. Quadrants areas within the SN were determined with a planimeter and neuronal density was expressed as neurons/mm2for 10 Parkinson's disease (PD) cases, 29 incidental Lewy body cases, and 178 controls with neither condition. Mean densities in all quadrants were significantly lower in the PD group compared with the other groups (p= 0.006). This relationship was strongest in the ventrolateral quadrant. In a subgroup of 50 controls who were examined with the Unified Parkinson's Disease Rating Scale an average of 2.1 years prior to death, there was an association of stooped posture (p= 0.009), postural instability (p= 0.013), body bradykinesia (p= 0.048), and gait disturbance (p= 0.05) with neuron density in the dorsolateral quadrant; and impaired speech (p= 0.014), abnormal facial expression (p= 0.022), and difficulty rising from a chair (p= 0.032) with neuron density in the dorsomedial quadrant. There was a significant association of increasing number of signs present with decreasing neuron density in both quadrants (p= 0.001 for trend). Low SN neuron density may be the basis for parkinsonian signs in the elderly without PD. Ann Neurol 2004

To evaluate the association of fasting insulin level to incident dementia in a cohort of elderly men.

To assess the association between sleep-disordered breathing and cognitive functioning in an elderly cohort of Japanese-American men.

Clinicopathologic data from 285 autopsies were analyzed. The decedents were long-standing participants in the Honolulu-Asia Aging Study, a prospective epidemiologic investigation of stroke, neurodegenerative diseases, and aging. We assessed the prevalence at death of four primary neuropathologic processes using specific microscopic lesions as indicators. An algorithm was developed to assign each decedent to one of six subsets, corresponding to pathologic dominance by microvascular lesions (14 of decedents), Alzheimer lesions (12), hippocampal sclerosis (5), cortical Lewy bodies (5), codominance by two or more primary processes (9), or without a dominant pathologic process recognized (55). Definite or probable dementia had been identified in 118 of the decedents. The proportions of men in each subset identified as demented were (in the same order) 57, 53, 79, 57, 76, and 25. In this autopsied panel of older Japanese-American men, the importance of microvascular lesions as a likely explanation for dementia was nearly equal to that of Alzheimer lesions. The cerebrovascular lesion type most essentially and inclusively related to dementia was multiple microinfarction.

Inflammatory responses are associated with cardiovascular disease and may be associated with dementing disease. We evaluated the long-term prospective association between dementia and high-sensitivity C-reactive protein, a nonspecific marker of inflammation. Data are from the cohort of Japanese American men who were seen in the second examination of the Honolulu Heart Program (1968–1970) and subsequently were reexamined 25 years later for dementia in the Honolulu-Asia Aging Study (1991–1996). In a random subsample of 1,050 Honolulu-Asia Aging Study cases and noncases, high-sensitivity C-reactive protein concentrations were measured from serum taken at the second examination; dementia was assessed in a clinical examination that included neuroimaging and neuropsychological testing and was evaluated using international criteria. Compared with men in the lowest quartile (&lt;0.34mg/L) of high-sensitivity C-reactive protein, men in the upper three quartiles had a 3-fold significantly increased risk for all dementias combined, Alzheimer's disease, and vascular dementia. For vascular dementia, the risk increased with increasing quartile. These relations were independent of cardiovascular risk factors and disease. These data support the view that inflammatory markers may reflect not only peripheral disease, but also cerebral disease mechanisms related to dementia, and that these processes are measurable long before clinical symptoms appear.

In many community-based studies on the incidence of dementia, a target population is screened and a subsample is clinically evaluated at baseline and follow-up. Incidence rates are affected by missed cases at both exams and this complicates the estimation of these rates. Recent work proposes a regression-based technique for joint estimation of prevalence and incidence and suggests the use of surrogate information obtained on the entire cohort at both times to calculate the expected score equation contribution for individuals missing clinical exams at one or both times. This helps to quantify the impact of missed diagnosis upon the incidence estimates and their confidence intervals. We extend this work to the setting of subtypes of dementia for use in the Honolulu–Asia Aging Study on incidence of dementia. The technique is applied using two separate models for the effect of age on dementia incidence. Subsequently, shrinkage estimation methods are applied to provide more precise estimates of the rates. Published in 2000 by John Wiley & Sons, Ltd.

Objective:To examine associations of midlife tofu consumption with brain function and structural changes in late life.Methods:The design utilized surviving participants of a longitudinal study established in 1965 for research on heart disease, stroke, and cancer. Information on consumption of selected foods was available from standardized interviews conducted 1965–1967 and 1971–1974. A 4-level composite intake index defined “low-low” consumption as fewer than two servings of tofu per week in 1965 and no tofu in the prior week in 1971. Men who reported two or more servings per week at both interviews were defined as “high-high” consumers. Intermediate or less consistent “low” and “high” consumption levels were also defined. Cognitive functioning was tested at the 1991–1993 examination, when participants were aged 71 to 93 years (n=3734). Brain atrophy was assessed using neuroimage (n=574) and autopsy (n=290) information. Cognitive function data were also analyzed for wives of a sample of study participants (n=502) who had been living with the participants at the time of their dietary interviews.Results:Poor cognitive test performance, enlargement of ventricles and low brain weight were each significantly and independently associated with higher midlife tofu consumption. A similar association of midlife tofu intake with poor late life cognitive test scores was also observed among wives of cohort members, using the husband’s answers to food frequency questions as proxy for the wife’s consumption. Statistically significant associations were consistently demonstrated in linear and logistic multivariate regression models. Odds ratios comparing endpoints among “high-high” with “low-low” consumers were mostly in the range of 1.6 to 2.0.Conclusions:In this population, higher midlife tofu consumption was independently associated with indicators of cognitive impairment and brain atrophy in late life.

Estimates of the prevalence rates for dementia vary significantly among countries. Such variation may be explained, at least in part, by methodologic differences in studies. The disparities in prevalence rates of dementia subtypes, particularly Alzheimer’s disease and multi-infarct dementia, are especially apparent in studies conducted in Eastern and Western countries. In Japan and China, the prevalence of multi-infarct dementia exceeds that of Alzheimer’s disease, whereas in the West, Alzheimer’s disease predominates in the vast majority of studies. Clearly, cross-cultural studies of incidence using standard methods are needed to investigate whether a true difference in risk exists, and which risk factors differentially contribute to this variation. Migrant studies of genetically homogeneous populations offer a unique opportunity to answer these questions. This article explores the value of migrant studies, their application to etiologic questions of dementia and its subtypes, and recommendations concerning how to conduct such studies.

The Cognitive Abilities Screening Instrument (CASI) has a score range of 0 to 100 and provides quantitative assessment on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment. Scores of the Mini-Mental State Examination, the Modified Mini-Mental State Test, and the Hasegawa Dementia Screening Scale can also be estimated from subsets of the CASI items. Pilot testing conducted in Japan and in the United States has demonstrated its cross-cultural applicability and its usefulness in screening for dementia, in monitoring disease progression, and in providing profiles of cognitive impairment. Typical administration time is 15 to 20 minutes. Record form, manual, videotape of test administration, and quizzes to qualify potential users on the administration and scoring of the CASI are available upon request.

A cohort of 3,595 white women aged 40–77 years was followed for an average of 10 years during which 84 new cases of hip fracture were identified. Triceps skinfold thickness and arm muscle area measured at baseline were examined as possible risk factors for hip fracture controlling for physical activity, height, menopausal status, calcium consumption, and smoking. Of these variables only arm muscle area, triceps skinfold thickness, and activity in recreation were independent predictors of hip fracture incidence using the Cox proportional hazards model. After adjustment, the estimated relative risk of hip fracture was approximately two for an increment of each anthropometric indicator (adjusted for the other) equivalent to comparing those at the 25th percentile to those at the 75th percentile (maximum width of 95% confidence intervals, 1.2–2.9). Risk of hip fracture was approximately two‐fold for persons who reported little recreational exercise compared to persons who reported much recreational exercise (95% confidence interval, 1.2–3.2).

The occurrence of pressure sores during a follow‐up period of approximately 10 years is documented for a US nationwide cohort aged 55 to 75 years at baseline. Using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow‐up Study, those who developed pressure sores were identified through death certificates, hospital discharge summaries and self‐report or proxy‐report. During the follow‐up period, pressure sores were identified in 113 of the 5,193 respondents (2.2%) for whom follow‐up information was available. Incidence over the follow‐up period was 1.7% for those aged 55 to 69 at baseline and rose to 3.3% for those 70 to 75 years old. Risk factors for pressure sore development were evaluated using data collected in NHANES I at baseline. Those with identified pressure sores were compared with the remainder of their cohort and also with a control group matched on age and length of longest hospitalization or nursing home admission. Significantly increased risk for pressure sore development was found for those who at baseline were current smokers, reported being relatively inactive, had poor self‐assessed health status and who were found on physician's exam to have dry or scaling skin. Neurologic abnormality on the physician's exam and anemia at baseline were also associated with increased risk of pressure sores, although these associations were of borderline statistical significance.

Information concerning bowel habits was gathered from a representative sample of 14,407 United States adults in the first National Health and Nutrition Examination Survey in 1971–1975 and approximately 10 years later among the same individuals. The prevalence of self-reported constipation, diarrhea, infrequent defecation (three or fewer bowel movements per week), and frequent defecation (two or more bowel movements per day) increased with aging. Women were more likely than men (P<0.05) to report constipation (20.8% compared to 8.0%) and infrequent defecation (9.1% compared to 3.2%). Blacks were more likely than whites to report infrequent defecation (P<0.05). Older respondents reporting constipation were more likely to use laxatives or stool softeners than younger respondents reporting constipation, but they were also less likely to have infrequent defecation. To evaluate factors predictive of impaired bowel function, case definitions were created using information concerning complaint of constipation, laxative use, frequency of defecation, and stool consistency. Female gender, black race, fewer years of education, low physical activity, and symptoms of depression were independent risk factors for impaired bowel function. This study provides national estimates of bowel complaints and their natural history and examines possible risk factors for constipation.

In 1976–1978, a battery of eight neuropsychologic tests was administered to 2,123 participants in the Framingham Study aged 55 to 89 yr. The battery was designed to sample multiple areas of cognitive function including language skills, memory, learning, reproduction of designs, attention, and abstract thinking. Performance is described for several groups in this population: a large community-dwelling sample, those with hearing impairments, and those with documented strokes. Performance is described by age, sex, and education strata for the community sample. This normative information should be useful for interpreting individual test performance on neuropsychological tests.

Endogenous serum pyrogen from rabbits produced fever in dogs and vice versa. Pyrogenicity of EP in the homologous species was dose related, but this was not the case in the heterologous species. Human serum obtained from patients both during fever and after defervescence produced fever in rabbits. These results suggest that pyrogenicity of EP in animals of different species is probably a non-specific phenomenon.

Rabbits acutely depleted of serum potassium or made chronically potassium deficient released more endogenous pyrogen following a constant pyrogenic stimulus than normokalemic controls. Increase of serum potassium to levels of 8.8 meq/1 did not alter the animals' ability to release endogenous pyrogen, and production of hypercalcemia also had no effect. These observations confirm the inhibitory effect of potassium on release of pyrogen from leukocytes in vitro.

Administration of nitrofurazone to rabbits did not interfere with the animals'ability to release endogenous serum pyrogen following administration of typhoid vaccine. Incubation of endogenous serum pyrogen with nitrofurazone did not alter its pyrogenicity.

A successful, relatively inexpensive method is described for freezing peripheral lymphocytes. These lymphocytes when thawed and grown in the presence of antigens transformed at approximately the same rate as unfrozen control cultures from the same individuals. A method is also described for successfully culturing lymphocytes which adhere to the surfaces of cover slips or petri plates previously treated with 0.5% gelatin. Rates of lymphocyte transformation in these cultures were similar to those encountered in culture tubes.

A semiquantitative assay for endogenous pyrogen in serum is described. The test depends on using at least 3-4 recipients at at least 4 ranges of dosage, and the use of the fever index rather than height of the fever curve. This permits construction of a dose response curve which delineates the sensitive range of pyrexia. The minimum pyrogenic dose can then be calculated and should serve as a useful standard for comparison of different pyrogenic substances.

IN many mouse strains, RNA tumour virus information is transmitted vertically (inherited) perhaps as part of the cell genome1,2. The activation of type C virus replication in cells from low leukaemia incidence mouse strains3and from ‘virus-free’ cell lines4by halogenated pyrimidines suggests that all mouse cells may contain murine leukaemia virus (MuLV) information, often in an unexpressed form. Indeed, proponents of the ‘oncogene’ hypothesis have predicted a complete copy of type C virus information in the genome of all somatic cells2.

The human polyomavirus JC (JCV) infects glial cells and is the etiologic agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy. JCV can infect granule cell neurons of the cerebellum, causing JCV granule cell neuronopathy and cortical pyramidal neurons in JCV encephalopathy. Whether JCV also infects neurons in other areas of the CNS is unclear. We determined the prevalence and pattern of JCV infection of the hippocampus in archival samples from 28 patients with known JCV infection of the CNS and 66 control subjects. Among 28 patients, 11 (39.3%) had JCV infection of hippocampus structures demonstrated by immunohistochemistry. Those included gray matter (dentate gyrus and cornu ammonis, subiculum) in 11/11 and afferent or efferent white matter tracts (perforant path, alveus, fimbria) in 10/11. In the hippocampus, JCV infected granule cell and pyramidal neurons, astrocytes, and oligodendrocytes. Although glial cells expressed either JCV regulatory T Antigen or JCV VP1 capsid protein, infected neurons expressed JCV T Antigen only, suggesting an abortive/restrictive infection. None of the 66 control subjects had evidence of hippocampal JCV protein expression by immunohistochemistry or JCV DNA by in situ hybridization. These results greatly expand our understanding of JCV pathogenesis in the CNS.