Hemostasis biomarkers and incident cognitive impairment: the REGARDS study.

Essentials Cognitive disorders are increasing and vascular risk factors play a role in this. We performed a nested case control study of hemostasis biomarkers and cognitive impairment (CI). Higher baseline fibrinogen, factor VIII and D-dimer were related to incident CI over 3.5 years. Adjusted for other risk factors, 2+ abnormal markers (but not single ones) led to higher risk. SUMMARY: Background Vascular risk factors are associated with cognitive impairment, a condition that imposes a substantial public health burden. We hypothesized that hemostasis biomarkers related to vascular disease would be associated with the risk of incident cognitive impairment. Methods We performed a nested case-control study including 1082 participants with 3.5 years of follow-up in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30 239 black and white Americans aged ≥ 45 years. Participants were free of stroke or cognitive impairment at baseline. Baseline D-dimer, fibrinogen, factor VIII and protein C levels were measured in 495 cases who developed cognitive impairment during follow-up (based on abnormal scores on two or more of three cognitive tests) and 587 controls. Results Unadjusted odds ratios (ORs) for incident cognitive impairment were 1.32 (95% confidence interval [CI] 1.02-1.70) for D-dimer > 0.50 µg mL-1 , 1.83 (95% CI 1.24-2.71) for fibrinogen > 90th percentile, 1.63 (95% CI 1.11-2.38) for FVIII > 90th percentile, and 1.10 (95% CI 0.73-1.65) for protein C < 10th percentile. There were no differences in associations by race or region. Adjustment for demographic, vascular and health behavior risk factors attenuated these associations. However, having at least two elevated biomarkers was associated with incident cognitive impairment, with an adjusted OR of 1.73 (95% CI 1.10-2.69). Conclusion Elevated D-dimer, fibrinogen and FVIII levels were not associated with the occurrence of cognitive impairment after multivariable adjustment; however, having at least two abnormal biomarkers was associated with the occurrence of cognitive impairment, suggesting that the burden of these biomarkers is relevant.

Longitudinal Association between Selenium Levels and Hypertension in a Rural Elderly Chinese Cohort.

OBJECTIVES: Results from previous studies have been inconsistent on the association between selenium and hypertension, and very few studies on this subject have focused on the elderly population. The purpose of this study is to examine the relationship between selenium level and hypertension in a rural elderly Chinese cohort. DESIGN: A longitudinal study was implemented and data were analyzed using logistic regression models and Cox proportional hazards regression model adjusting for potential confounders. The associations between selenium level and prevalent hypertension at baseline and between selenium and incident hypertension were examined. SETTING: Community-based setting in four rural areas in China. SUBJECTS: A total of 2000 elderly aged 65 years and over (mean 71.9±5.6 years) participated in this study. MEASUREMENTS: Nail selenium levels were measured in all subjects at baseline. Blood pressure measures and self-reported hypertension history were collected at baseline, 2.5 years and 7 years later. Hypertension was defined as systolic blood pressure 140 mmHg or higher, diastolic blood pressure 90 mmHg or higher, or reported use of anti-hypertensive medication. RESULTS: The rate of baseline hypertension was 63.50% in this cohort and the mean nail selenium level is 0.413±0.183µg/g. Multi-covariate adjusted cross-sectional analyses indicated that higher selenium level was associated with higher blood pressure measures at baseline and higher rates of hypertension. For the 635 participants with normal blood pressure at baseline, 360 had developed hypertension during follow-up. The incidence rate for hypertension was 45.83%, 52.27%, 62.50%, 70.48%, and 62.79% from the first selenium quintile to the fifth quintile respectively. Comparing to the lowest quintile group, the hazard ratios were 1.41 (95%CI: 1.03 to1.94), 1.93 (95%CI: 1.40 to 2.67), 2.35 (95%CI: 1.69 to 3.26) and 1.94 (95%CI: 1.36 to 22.77) for the second selenium quintile to the fifth quintile respectively. CONCLUSIONS: Our findings suggest that high selenium may play a harmful role in the development of hypertension. Future studies are needed to confirm our findings and to elucidate a plausible biological mechanism.

Vascular risk factors and cognitive impairment in a stroke-free cohort.

OBJECTIVE: To examine vascular risk factors, as measured by the Framingham Stroke Risk Profile (FSRP), to predict incident cognitive impairment in a large, national sample of black and white adults age 45 years and older. METHODS: Participants included subjects without stroke at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with at least 2 cognitive function assessments during the follow-up (n = 23,752). Incident cognitive impairment was defined as decline from a baseline score of 5 or 6 (of possible 6 points) to the most recent follow-up score of 4 or less on the Six-item Screener (SIS). Subjects with suspected stroke during follow-up were censored. RESULTS: During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment. Baseline FSRP score was associated with incident cognitive impairment. An adjusted model revealed that male sex (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.43-1.77), black race (OR = 2.09, 95% CI 1.88-2.35), less education (less than high school graduate vs college graduate, OR = 2.21, 95% CI 1.88-2.60), older age (10-year increments, OR = 2.11, per 10-year increase in age, 95% CI 2.05-2.18), and presence of left ventricular hypertrophy (LVH, OR = 1.29, 95% CI 1.06-1.58) were related to development of cognitive impairment. When LVH was excluded from the model, elevated systolic blood pressure was related to incident cognitive impairment. CONCLUSIONS: Total FSRP score, elevated blood pressure, and LVH predict development of clinically significant cognitive dysfunction. Prevention and treatment of high blood pressure may be effective in preserving cognitive health.

Hypertension and incident dementia in community-dwelling elderly Yoruba Nigerians.

OBJECTIVES: To investigate the relationship between hypertension and dementia incidence in community-dwelling elderly Yoruba (aged 70 years and above) because of sparse information on dementia and its risk factors in developing countries. MATERIALS AND METHODS: Community-based, prospective study of consenting elderly Yoruba using two-stage design. Blood pressure was measured during the baseline evaluation at 2001 and hypertension was defined as BP ≥ 140/90 mmHg. Diagnosis of dementia and normal cognition was by consensus using standard criteria. Non-demented subjects from the 2001 evaluation wave were re-evaluated during the 2004 and 2007 waves for dementia. Logistic regression was used to examine the association of baseline hypertension and incident dementia, after adjusting for age, gender, education, and histories of stroke and smoking. P-values <0.05 were considered significant. RESULTS: During the 6-year follow-up, 120 individuals developed dementia, while 1633 remained non-demented. The frequency of hypertension in the demented group was significantly higher than in the non-demented (70.0% vs 60.2%, P = 0.034). Baseline hypertension was a significant risk factor for dementia (OR = 1.52; 95% CI 1.01-2.30). Higher systolic, diastolic or pulse pressure was associated with increased risk (P < 0.05). Participants with diastolic BP ≥ 90 mmHg were at a significantly greater risk than those with readings below 70 mmHg (OR = 1.65; 95% CI 1.01-2.69). CONCLUSIONS: Hypertension was associated with increased risk of dementia in elderly Yoruba and its appropriate treatment may lower the risk.

Use of anticholinergics and the risk of cognitive impairment in an African American population.

BACKGROUND: Anticholinergic properties of certain medications often go unrecognized, and are frequently used by the elderly population. Few studies have yet defined the long-term impact of these medications on the incidence of cognitive impairment. METHODS: We report a 6-year longitudinal, observational study, evaluating 1,652 community-dwelling African American subjects over the age of 70 years who were enrolled in the Indianapolis-Ibadan Dementia Project between 2001 and 2007 and who had normal cognitive function at baseline. The exposure group included those who reported the baseline use of possible or definite anticholinergics as determined by the Anticholinergic Cognitive Burden scale. Our main outcome measure was the incidence of cognitive impairment, defined as either dementia or cognitive impairment not dementia, or poor performance on a dementia screening instrument during the follow-up period. RESULTS: At baseline, 53% of the population used a possible anticholinergic, and 11% used a definite anticholinergic. After adjusting for age, gender, educational level, and baseline cognitive performance, the number of definite anticholinergics was associated with an increased risk of cognitive impairment (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.07-1.99; p = 0.02), whereas the number of possible anticholinergics at baseline did not increase the risk (OR 0.96, 95% CI 0.85-1.09; p = 0.55). The risk of cognitive impairment among definite anticholinergic users was increased if they were not carriers of the APOE epsilon4 allele (OR 1.77, 95% CI 1.03-3.05; p = 0.04). CONCLUSIONS: Limiting the clinical use of definite anticholinergics may reduce the incidence of cognitive impairment among African Americans.

Cognitive speed of processing and functional declines in older cancer survivors: an analysis of data from the ACTIVE trial.

It has been suggested that chemotherapy treatment for cancer may contribute to cognitive decline in older cancer survivors. This issue is particularly important given that subtle cognitive impairment, particularly in cognitive processing speed, can affect functional status and quality of life for older adults. Multivariate regression of data from a longitudinal randomized controlled trial of older adults revealed a trend towards decreased performance after cancer treatment with chemotherapy on several functional measures associated with processing speed (as compared with matched individuals who did not have cancer). Additional analyses revealed that a subset of the chemotherapy-treated adults demonstrated a reliable negative change on several measures of processing speed. While inconclusive, this hypothesis generating work suggests that cognitive dysfunction following cancer treatment may contribute to disability observed in older cancer survivors. Further research is needed to determine the significance of the relationship between cognitive and functional impairment in older cancer survivors.

Association of higher diastolic blood pressure levels with cognitive impairment.

BACKGROUND: We evaluated the cross-sectional relationship of blood pressure (BP) components with cognitive impairment after adjusting for potential confounders. METHODS: Reasons for Geographic and Racial Differences in Stroke (REGARDS) is a national, longitudinal population cohort evaluating stroke risk in 30,228 black and white men and women >or=45 years old. During the in-home visit, BP measurements were taken as the average of 2 measurements using a standard aneroid sphygmomanometer. Excluding participants with prior stroke or TIA, the present analysis included 19,836 participants (enrolled from December 2003 to March 2007) with complete baseline physical and cognitive evaluations. Incremental logistic models examined baseline relationships between BP components (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) and impaired cognitive status (score of

Risk factors for incident Alzheimer's disease in African Americans and Yoruba.

INTRODUCTION: The incidence rate of Alzheimer's disease (AD) was found to be 2 times lower in Yoruba than in African Americans. This study was aimed at identifying the factors associated with increased risk of incident AD in the two communities. METHODOLOGY: A two-stage design with initial screening using the CSI'D followed by neuropsychological test battery, relations' interview and physician assessment in a sub-sample.NINCDS-ADRDA criteria were met for AD. The risk factor variables assessed included demographic, lifestyle, medical and family history items. RESULTS: In the Yoruba, AD was associated with age (OR = 1.07) and female gender (OR = 2.93). In African Americans, age (OR = 1.09) and rural living (OR = 2.08) were the significant risk factors, while alcohol was protective (OR = 0.49). DISCUSSION: Age was a significant risk factor for AD at both sites. The higher risk of incident AD in the Yoruba female, and in African Americans who resided in rural areas in childhood were similar with the prevalence cases. Alcohol emerged a protective factor in African Americans. More studies are required, including biological measurements, to adequately explain the differences in rates.

The development of a semi-structured home interview (CHIF) to directly assess function in cognitively impaired elderly people in two cultures.

BACKGROUND: Assessing function is a crucial element in the diagnosis of dementia. This information is usually obtained from key informants. However, reliable informants are not always available. METHODS: A 10-item semi-structured home interview (the CHIF, or Clinician Home-based Interview to assess Function) to assess function primarily by measuring instrumental activities of daily living directly was developed and tested for inter-rater reliability and validity as part of the Indianapolis-Ibadan dementia project. The primary validity measurements were correlations between scores on the CHIF and independently gathered scores on the Blessed Dementia Scale (from informants) and the Mini-mental State Examination (MMSE). Sensitivities and specificities of scores on the CHIF and receiver operator characteristic (ROC) curves were constructed with dementia as the dependent variable. RESULTS: Inter-rater reliability for the CHIF was high (Pearson's correlation coefficient 0.99 in Indianapolis and 0.87 in Ibadan). Internal consistency, in both samples, was good (Cronbach's alpha 0.95 in Indianapolis and 0.83 in Ibadan). Scores on the CHIF correlated well with the Blessed Dementia scores at both sites (-0.71, p < 0.0001 for Indianapolis and -0.56, p < 0.0001 for Ibadan) and with the MMSE (0.75, p < 0.0001 for Indianapolis and 0.44, p < 0.0001 for Ibadan). For all items at both sites, the subjects without dementia performed significantly better than those with dementia. The area under the ROC curve for dementia diagnosis was 0.965 for Indianapolis and 0.925 for Ibadan. CONCLUSION: The CHIF is a useful instrument to assess function directly in elderly participants in international studies, particularly in the absence of reliable informants.

Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba.

OBJECTIVE: To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. METHODS: Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. RESULTS: Logistic regression models showed interaction after adjusting for age and gender between APOE-epsilon4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p= 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-epsilon4 allele, but not in those with APOE-epsilon4. There was no significant association between levels of triglycerides and AD risk in those without APOE-epsilon4. CONCLUSIONS: There was a significant interaction between cholesterol, APOE-epsilon4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies.

Caring for individuals with dementia: the Nigerian experience.

Recent epidemiological data, mainly from cross-cultural studies, have revealed that the burden of dementia and Alzheimer's disease (AD) the most common type, is significantly lower in developing than in the industrialized countries. Caring for individuals with dementia is a major consideration because most developing countries do not have the resources to provide comprehensive care in institutions. Home care that is practiced is ideal given the cultural scenario especially with the extended family support. Public policies on the care of the elderly however need to be well articulated and implemented. Hypertension was the most frequent medical co-morbidity of the demented subjects and about a third of subjects with AD were hypertensive, which may support vascular hypothesis in AD pathogenesis. The important behavioural disturbances experienced by caregivers and the associated stress levels were highlighted. The model used on the Indianapolis-Ibadan Dementia Study which involves periodic home visits, and empowerment of caregivers through regular meetings is envisaged to make caring for these individuals easier and adaptable in other African communities.

Cognitive impairment in community-dwelling older Nigerians: clinical correlates and stability of diagnosis.

To determine correlates and outcome of cognitive impairment without dementia in community-dwelling elderly Nigerians. A total of 2487 community residents aged 65 years and over were screened using the Community Screening Interview for Dementia. A subset of 423 individuals received diagnostic clinical evaluation. Participants were diagnosed normal, demented, or cognitive impairment no dementia (CIND). Follow-up clinical diagnostic evaluation was conducted on CIND subjects approximately 2 years later. One hundred and fifty-two persons were diagnosed CIND. Eighty-seven CIND subjects were seen at follow-up assessment, 14 (16.1%) had converted to dementia, 22 (25.3%) reverted to normal, and 51 (58.6%) remained CIND. No baseline factors predicted later development of dementia amongst the CIND subjects. CIND subjects who reverted to normal tended to be male and to have higher baseline cognitive scores. Apolipoprotein status was not related to diagnosis at follow-up. CIND is common in community-dwelling Nigerians. Although the outcome is variable, it does represent a high-risk group for subsequent dementia.

Prevalence of cognitive impairment: data from the Indianapolis Study of Health and Aging.

BACKGROUND: The epidemiology and natural history of cognitive impairment that is not dementia is important to the understanding of normal aging and dementia. OBJECTIVE: To determine the prevalence and outcome of cognitive impairment that is not dementia in an elderly African American population. METHOD: A two-phase, longitudinal study of aging and dementia. A total of 2212 community-dwelling African American residents of Indianapolis, IN, aged 65 and older were screened, and a subset (n = 351) received full clinical assessment and diagnosis. Subsets of the clinically assessed were seen again for clinical assessment and rediagnosis at 18 and 48 months. Weighted logistic regression was used to generate age-specific prevalence estimates. RESULTS: The overall rate of cognitive impairment among community-dwelling elderly was 23.4%. Age-specific rates indicate increasing prevalence with increasing age: 19.2% for ages 65 to 74 years, 27.6% for ages 75 to 84 years, and 38.0% for ages 85+ years. The most frequent cause of cognitive impairment was medically unexplained memory loss with a community prevalence of 12.5%, followed by medical illness-associated cognitive impairment (4.0% prevalence), stroke (3.6% prevalence), and alcohol abuse (1.5% prevalence). At 18-month follow-up, 26% (17/66) of the subjects had become demented. CONCLUSIONS: Cognitive impairment short of dementia affects nearly one in four community-dwelling elders and is a major risk factor for later development of dementia.

Performance of elderly African American and White community residents on the CERAD Neuropsychological Battery.

The CERAD Neuropsychological Battery, includes 7 measures: Verbal Fluency; Modified Boston Naming; Mini-Mental State: Word List Learning, Recall and Recognition; Constructional Praxis. It was originally developed to evaluate patients with a clinical diagnosis of Alzheimer's disease, but is increasingly used in epidemiological studies of the incidence and prevalence of dementia in the elderly. The current study reports norms for African American and White representative community residents 71 years of age and older in North Carolina, and compares performance with that of African Americans in Indianapolis and with Whites in the Monongahela Valley, Pennsylvania. For all 3 studies, increased education and younger age was related to better performance on each of the 7 measures. Sex differences, when present, tended to favor women. Although on average African Americans performed more poorly than Whites, with demographic characteristics controlled, no significant racial differences were found in the North Carolina sample. Both African American and White participants in North Carolina performed more poorly than their racial counterparts in the other 2 studies, possibly because of selection-induced differences in health and educational status. Nevertheless, the use of an identical evaluation battery, such as the CERAD neuropsychologic instrument, facilitates comparisons not otherwise possible, and should be encouraged.

Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, Indiana.

CONTEXT: Alzheimer disease (AD) represents a major and increasing public health problem. If populations were identified with significantly lower or higher incidence rates of AD, the search for risk factors in the genesis of AD could be greatly enhanced. OBJECTIVE: To compare incidence rates of dementia and AD in 2 diverse, elderly community-dwelling populations. DESIGN: The Indianapolis-Ibadan Dementia Project, a longitudinal, prospective population-based study consisting of a baseline survey (1992-1993) and 2 subsequent follow-up waves after 2 years (1994-1995) and 5 years (1997-1998). Each wave followed a 2-stage design, with an in-home screening interview followed by a full diagnostic workup of a subsample of participants based on screening performance. SETTING AND PARTICIPANTS: A total of 2459 community-dwelling Yoruba residents of Ibadan, Nigeria, without dementia, and 2147 community-dwelling African American residents of Indianapolis, Ind, without dementia (all aged 65 years or older). The cohorts were followed up for a mean of 5.1 years and 4.7 years, respectively. MAIN OUTCOME MEASURES: Incident cases of dementia and AD in each of the 2 populations. RESULTS: The age-standardized annual incidence rates were significantly lower among Yoruba than among African Americans for dementia (Yoruba, 1.35% [95% confidence interval [CI], 1.13%-1.56%]; African Americans, 3.24% [95% CI, 2.11%-4.38%]) and for AD (Yoruba, 1.15% [95% CI, 0.96%-1.35%]; African Americans, 2.52% [95% CI, 1.40%-3.64%]). CONCLUSION: This is the first report of incidence rate differences for dementia and AD in studies of 2 populations from nonindustrialized and industrialized countries using identical methods and the same group of investigators in both sites. Further explorations of these population differences may identify potentially modifiable environmental or genetic factors to account for site differences in dementia and AD.

Morbidity pattern in a sample of elderly Nigerians resident in Idikan community, Ibadan.

We documented the pattern of medical illnesses in 613 elderly Nigerians (398 females and 215 males) resident in Idikan community in Ibadan city. Their ages ranged from 65 to 110 years with a mean of 76.2 years. Medical disorders diagnosed either singly or in combinations were diagnosed in 364 (59.4%) subjects and there was no gender association. Cardiovascular problems were the commonest and high blood pressure (27.8%) was the most frequent diagnosis. Only 5 of the hypertensive subjects were aware of that diagnosis and were on regular medications. The complications presented with included heart failure and stroke. Visual impairment (12.1%) mainly due to cataracts and osteoarthritis (6.7%) in that order were next in frequency. The most frequent neurological disorders were hearing impairment and movement disorders. The other conditions encountered were similar to the findings in previous studies in this environment, and the usual findings in studies focusing on this age-group in other countries. The presence of morbidity was significantly associated with increasing age and poor performance on screening. The latter increased the probability of being selected for clinical examination with detection of medical problems or could suggest associated cognitive impairment. The prevalence of systemic hypertension was not different from findings in other communities in people of similar age groups. This study emphasises the role of hypertension as a major cause of morbidity in this community and stresses the need for increased health awareness especially with regards to regular checking of blood pressure so as to avoid complications.

Ectopic white matter neurons, a developmental abnormality that may be caused by the PSEN1 S169L mutation in a case of familial AD with myoclonus and seizures.

We report clinical, neuropathologic and molecular genetic data from an individual affected by a familial Alzheimer disease (AD) variant. The proband had an onset of dementia at age 29 followed by generalized seizures a year later. He died at age 40. Neuropathologically, he had severe brain atrophy and characteristic histopathologic lesions of AD. Three additional neuropathologic features need to be emphasized: 1) severe deposition of Abeta in the form of diffuse deposits in the cerebral and cerebellar cortices, 2) numerous Abeta deposits in the subcortical white matter and in the centrum semiovale, and 3) numerous ectopic neurons, often containing tau-immunopositive neurofibrillary tangles, in the white maner of the frontal and temporal lobes. A molecular genetic analysis of DNA extracted from brain tissue of the proband revealed a S169L mutation in the Presenilin 1 (PSEN1) gene. The importance of this case lies in the presence of ectopic neurons in the white matter, early-onset seizures, and a PSEN1 mutation. We hypothesize that the PSEN1 mutation may have a causal relationship with an abnormality in neuronal development.

Senile dementia associated with amyloid beta protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-epsilon4 allele.

Amyloid beta protein deposition in cortical and leptomeningeal vessels, causing the most common type of cerebral amyloid angiopathy, is found in sporadic and familial Alzheimer's disease (AD) and is the principal feature in the hereditary cerebral hemorrhage with amyloidosis, Dutch type. The presence of the Apolipopriotein E (APOE)-epsilon4 allele has been implicated as a risk factor for AD and the development of cerebral amyloid angiopathy in AD. We report clinical, pathological and biochemical studies on two APOE-epsilon4 homozygous subjects, who had senile dementia and whose main neuropathological feature was a severe and diffuse amyloid angiopathy associated with perivascular tau neurofibrillary pathology. Amyloid beta protein and ApoE immunoreactivity were observed in leptomeningeal vessels as well as in medium-sized and small vessels and capillaries in the parenchyma of the neocortex, hippocampus, thalamus, cerebellum, midbrain, pons, and medulla. The predominant peptide form of amyloid beta protein was that terminating at residue Val40, as determined by immunohistochemistry, amino acid sequence and mass spectrometry analysis. A crown of tau-immunopositive cell processes was consistently present around blood vessels. DNA sequence analysis of the Amyloid Precursor Protein gene and Presenilin-1 (PS-1) gene revealed no mutations. In these APOE-epsilon4 homozygous patients, the pathological process differed from that typically seen in AD in that they showed a heavy burden of perivascular tau-immunopositive cell processes associated with severe amyloid beta protein angiopathy, neurofibrillary tangles, some cortical Lewy bodies and an absence of neuritic plaques. These cases emphasize the concept that tau deposits may be pathogenetically related to amyloid beta protein deposition.

Trace element levels in drinking water and cognitive function among elderly Chinese.

The relation between trace element levels in drinking water and cognitive function was investigated in a population-based study of elderly residents (n = 1,016) in rural China in 1996-1997. Cognitive function was measured using a Chinese translation of the Community Screening Interview for Dementia. A mixed effects model was used to evaluate the effect of each of the elements on cognitive function while adjusting for age, sex, and educational level. Several of the elements examined had a significant effect on cognitive function when they were assessed in a univariate context. However, after adjustment for other elements, many of these results were not significant. There was a significant quadratic effect for calcium and a significant zinc-cadmium interaction. Cognitive function increased with calcium level up to a certain point and then decreased as calcium continued to increase. Zinc showed a positive relation with cognitive function at low cadmium levels but a negative relation at high levels.

Low education and childhood rural residence: risk for Alzheimer's disease in African Americans.

OBJECTIVE: To examine the relationship between level of education and childhood rural residence as possible risk factors for AD in African Americans in Indianapolis. BACKGROUND: Low level of education has been a risk factor for AD in some studies, but childhood rural residence has not been addressed in most of these studies. METHODS: A two-stage community-based prevalence study of AD was conducted in a random sample of 2,212 African Americans > or =65 years of age. A subsample of clinically assessed normal individuals (180) and individuals diagnosed with AD (43) were compared on the variables of rural/urban residence in childhood and low (< or =6 years) or high (> or =7 years) education. A logistic regression model was used with interaction between rural residence and low education to estimate odds ratios for the two risk factors combined, adjusting for age and gender. RESULTS: Odds ratios for AD: 6.5 (95% CI: 2.6 to 16.7) low education/rural residence; 0.5 (95% CI: 0.1 to 2.9) low education/urban residence; 1.5 (95% CI: 0.4 to 5.2) high education/rural residence, comparing with the group of high education/urban residence. CONCLUSION: Childhood rural residence, combined with < or =6 years of school, was associated with an increased risk of AD in this sample. It is possible that low education by itself is not a major risk factor for AD, but, rather, is a marker for other accompanying deleterious socioeconomic or environmental influences in childhood.