Effect of age, ethnicity, sex, cognitive status and APOE genotype on amyloid load and the threshold for amyloid positivity.

The threshold for amyloid positivity by visual assessment on PET has been validated by comparison to amyloid load measured histopathologically and biochemically at post mortem. As such, it is now feasible to use qualitative visual assessment of amyloid positivity as an in-vivo gold standard to determine those factors which can modify the quantitative threshold for amyloid positivity. We calculated quantitative amyloid load, measured as Standardized Uptake Value Ratios (SUVRs) using [18-F]florbetaben PET scans, for 159 Hispanic and non-Hispanic participants, who had been classified clinically as Cognitively Normal (CN), Mild Cognitive Impairment (MCI) or Dementia (DEM). PET scans were visually rated as amyloid positive (A+) or negative (A-), and these judgments were used as the gold standard with which to determine (using ROC analyses) the SUVR threshold for amyloid positivity considering factors such as age, ethnicity (Hispanic versus non-Hispanic), gender, cognitive status, and apolipoprotein E ε4 carrier status. Visually rated scans were A+ for 11% of CN, 39.0% of MCI and 70% of DEM participants. The optimal SUVR threshold for A+ among all participants was 1.42 (sensitivity = 94%; specificity = 92.5%), but this quantitative threshold was higher among E4 carriers (SUVR = 1.52) than non-carriers (SUVR = 1.31). While mean SUVRs did not differ between Hispanic and non-Hispanic participants;, a statistically significant interaction term indicated that the effect of E4 carrier status on amyloid load was greater among non-Hispanics than Hispanics. Visual assessment, as the gold standard for A+, facilitates determination of the effects of various factors on quantitative thresholds for amyloid positivity. A continuous relationship was found between amyloid load and global cognitive scores, suggesting that any calculated threshold for the whole group, or a subgroup, is artefactual and that the lowest calculated threshold may be optimal for the purposes of early diagnosis and intervention.

Association of white matter hyperintensity measurements on brain MR imaging with cognitive status, medial temporal atrophy, and cardiovascular risk factors.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are frequently characterized as markers of cerebrovascular disease, whereas medial temporal atrophy (MTA) is a recognized marker of Alzheimer disease (AD). Our purpose was to test the reliability of a visual rating system (VRS) in evaluating WMHs and MTA and in distinguishing healthy from cognitively impaired subjects. MATERIALS AND METHODS: Subjects (n = 192) enrolled in the Florida Alzheimer's Disease Research Center were diagnosed with no cognitive impairment, nonamnestic mild cognitive impairment (na-MCI), amnestic MCI (a-MCI), or probable AD. The severity of WMHs was assessed on T2-weighted fluid-attenuated inversion recovery axial MR images, and the severity of MTA was evaluated on 1.5-mm-thick coronal MR images by using a computer-based visual rating system. Cardiovascular risk factor scores were calculated as the sum of 10 independent cardiovascular risk factors. RESULTS: WMH and MTA scores were greater in subjects with probable AD, relative to those with no cognitive impairment and na-MCI. MTA scores differentiated subjects with a-MCI from those with no cognitive impairment and na-MCI. The total WMH score was significantly related to MTA (r = 0.39; P < .001) but not to cardiovascular risk factor scores (r = 0.07; P = not significant). The overall correct classification rate of probable AD versus no cognitive impairment by using MTA scores was 81.8%, improving to 86.5% when combined with WMH scores. CONCLUSIONS: Both MTA and WMH scores distinguished subjects with no cognitive impairment and probable AD. Combining MTA and WMH scores improved the correct classification rate, whereas WMH scores were significantly related to MTA scores, but not to cardiovascular risk factor scores. This finding suggests that among subjects with a-MCI and probable AD, WMHs on MR images are primarily associated with neurodegenerative disease.

Mild cognitive impairment: directions for future research.

Mild cognitive impairment (MCI), an intermediate state between normal aging and dementia, is characterized by acquired cognitive deficits, without significant decline in functional activities of daily living. Studies conducted on MCI have introduced new concepts regarding the possible distinctions between normal and pathologic aging of the brain. Neuroimaging and genetic testing have aided in the identification of individuals at increased risk for dementia. The measurement of change in cognitive and functional status in MCI remains challenging, because it requires instruments that are more sensitive and specific than those considered adequate for research in dementia. The authors provide an overview of the many methods that have been used to study MCI and directions that may help achieve greater uniformity in methodology. Considerable heterogeneity exists in research methodology used to study the epidemiology, thresholds for cognitive and functional impairment, rate of progression, risk factors, and defining subtypes of MCI. This article emphasizes the need for uniformity in the use of 1) appropriate and sensitive neuropsychological and functional measures to diagnose MCI, 2) reliable methods to determine progression or improvement of cognitive impairment, and 3) instruments in epidemiologic studies to establish population estimates for diverse ethnic and cultural groups. Greater consensus is needed to standardize definitions and research methodology for MCI, so as to make future studies more comparable and more useful for designing effective treatment strategies.

The Behavior Problems Checklist-Spanish: a preliminary study of a new scale for the assessment of depressive symptoms and disruptive behaviors in Hispanic patients with dementia.

Few instruments are available with which to measure behavioral and psychological signs and symptoms in Hispanic patients with dementia. Therefore, the aim of the current study was to develop and evaluate a 17-item scale adapted from the Revised Memory and Behavior Problems Checklist. This measure, the Behavior Problems Checklist-Spanish (BPC-S), assesses caregiver-reported symptoms of depression and disruption in patients with dementia. The sample for this study comprised 27 Spanish-speaking Hispanic patients and their family caregivers evaluated at a university-affiliated memory disorders center. All patients met diagnostic criteria for possible or probable Alzheimer's disease as set forth by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Disorders Association. Satisfactory convergent validity, discriminant validity, and internal consistency reliability were demonstrated for the Depression and Disruption subscales of the BPC-S. Both of these neuropsychiatric disturbances were related to heightened levels of caregiver burden. The results of this preliminary study suggest the BPC-S is a brief, psychometrically sound caregiver-report instrument to assess symptoms of mood disturbance and behavioral disruption in Hispanic patients with dementia. This instrument may have utility for both clinical and research purposes.

Category fluency test: normative data for English- and Spanish-speaking elderly.

Category fluency tasks are an important component of neuropsychological assessment, especially when evaluating for dementia syndromes. The growth in the number of Spanish-speaking elderly in the United States has increased the need for appropriate neuropsychological measures and normative data for this population. This study provides norms for English and Spanish speakers, over the age of 50, on 3 frequently used measures of category fluency: animals, vegetables, and fruits. In addition, it examines the impact of age, education, gender, language, and depressed mood on total fluency scores and on scores on each of these fluency measures. A sample of 702 cognitively intact elderly, 424 English speakers, and 278 Spanish speakers, participated in the study. Normative data are provided stratified by language, age, education, and gender. Results evidence that regardless of the primary language of the examinee, age, education, and gender are the strongest predictors of total category fluency scores, with gender being the best predictor of performance after adjusting for age and education. English and Spanish speakers obtained similar scores on animal and fruit fluency, but English speakers generated more vegetable exemplars than Spanish speakers. Results also indicate that different fluency measures are affected by various factors to different degrees.

Clinical characteristics of community-dwelling black Alzheimer's disease patients.

There is a relative dearth of studies examining the cognitive and neuropsychiatric features of black Alzheimer's disease (AD) patients in the United States. Therefore, this cross-sectional investigation reported on the prevalence and clinical correlates of depression and psychosis in a community-dwelling black AD sample. The study participants comprised 55 English-speaking black patients evaluated consecutively at a university-affiliated memory disorders clinic. All patients were evaluated utilizing standardized procedures and diagnosed with possible or probable AD according to the criteria established by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Disorders Association. The presence of neuropsychiatric symptoms, including major depression and psychosis (delusions or hallucinations) was established via a semistructured psychiatric interview with the patient and primary care giver. The level of global cognitive impairment was rated with the Mini-Mental State Examination. The results showed that major depression and psychosis were observed in 20% and 58% of the sample, respectively. Mood disturbance was linked with low education, whereas psychosis was associated with greater cognitive dysfunction. This study provides important insight into the clinical characteristics of community-dwelling black AD patients. It is clear that continued research in the area of ethnicity and dementia is warranted to better understand the clinical needs of blacks and other minority populations in the United States that are afflicted with AD.

Family history of dementia and current depression in nondemented community-dwelling older adults.

Since it has been postulated that mood disturbance in nondemented older adults may represent a prodromal feature of dementia for a subgroup of patients, it would be expected that patients with these symptoms would evidence a greater prevalence of family history of dementia. In a sample of 3225 community-dwelling cognitively intact elderly recruited from a free memory-screening program, we found that current depression was more common in participants with a positive versus a negative family history of dementia in first-degree relatives (17% versus 11%; Fisher's Exact Test, P < .0001). This relationship remained significant after controlling for age, education, gender, ethnicity, and Folstein Mini-Mental State Examination score (OR = 1.5; 95% CI = 1.2-1.9, Wald X2 = 15.5, P < .001). The results suggest that symptoms of depression may herald the onset of an incipient dementia syndrome in a subset of geriatric patients. Alternatively, the results may be indicative of familial aggregation of dementia and depression.

Predictors of positive and negative appraisal among Cuban American caregivers of Alzheimer's disease patients.

OBJECTIVE: This study investigated predictors of positive (satisfaction) and negative (burden) appraisal among Cuban American (CA) caregivers of Alzheimer's disease (AD) patients. DESIGN: Cross-sectional study of AD patients and their family caregivers. SETTING: A university-affiliated outpatient memory disorders clinic. SUBJECTS: A convenience sample of 40 CA family caregivers of patients diagnosed with probable or possible AD according to NINCDS-ADRDA diagnostic criteria. MEASURES: AD patients: Mini-Mental State Examination (MMSE), Blessed Dementia Scale (BDS) and the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Caregivers: Caregiving Burden Scale (CBS), Caregiving Satisfaction Scale (CSS), Perceived Emotional Support scale (PES) and the Short Form-36 Health Survey-General Health Index (GH). RESULTS: Appraised burden was predicted by increased patient behavioral pathology, female caregiver gender and lower levels of perceived emotional support. The association between older caregiver age and increased burden approached significance. Older caregiver age and higher levels of perceived social support were shown to predict appraised satisfaction. Post-hoc analyses also indicated that length of residence in the United States, a measure of acculturation, was not associated with positive or negative appraisal. CONCLUSION: Appraised burden and satisfaction represent important outcomes of dementia care that show relations with distinct factors among CA caregivers. It is clear that further research is warranted in order to ascertain the relationship of ethnicity or culture to the process and psychological consequences of dementia caregiving. Continued investigations into predictors of caregiving satisfaction are also recommended.

Relationship of behavioral and psychological symptoms to cognitive impairment and functional status in Alzheimer's disease.

OBJECTIVE: This cross-sectional study examined the relationship of behavioral and psychological symptoms to cognitive and functional impairment in Alzheimer's disease (AD). DESIGN: One hundred and fourteen patients were evaluated consecutively at a university-affiliated outpatient memory disorders clinic and diagnosed with possible or probable Alzheimer's disease (AD) according to NINCDS-ADRDA criteria. Subjects were assessed with the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD), Revised Memory and Behavior Problem Checklist (RMBPC), Blessed Dementia Scale (BDS), and Mini-Mental State Examination (MMSE). RESULTS: Several symptoms of behavioral pathology showed associations with MMSE scores, including activity disturbances, delusions, and hallucinations. After controlling for the variance associated with the MMSE, activity disturbances, diurnal disturbances, delusions, and hallucinations were linked with BDS scores. CONCLUSIONS: The results suggest that some non-cognitive symptoms may be related to the neurobiologic mechanisms underlying the increased cognitive dysfunction in AD. Specific symptoms of behavioral pathology may also impact a patient's ability to perform important self-maintenance behaviors.

Utility of a modified Mini-Mental State Examination with extended delayed recall in screening for mild cognitive impairment and dementia among community dwelling elders.

The objective of this study was to test the utility of additional delayed recall of the three recall items of the Folstein Mini Mental State Evaluation (MMSE) as a screening measure for mild cognitive impairment and dementia in the elderly. It used a cross-sectional study of subjects, who were administered a brief memory screening battery which included the MMSE and extended delayed recall of the three MMSE recall items at 5 minute intervals. The criteria for cognitive status was determined on the basis of the neurological and neuropsychological evaluation. One hundred and two elderly persons who were recruited through a memory screening program were diagnosed as cognitively normal (N=52), mild cognitively impaired (N=24), or demented (N=26). The observed sensitivity of 83.3% and specificity of 90.4% was achieved across three delayed recall trials in differentiating cases with mild cognitive impairment (without dementia) from individuals with normal cognition and was superior to the total MMSE score alone (sensitivity/specificity: 70.8%/84.6%). Cumulative recall for the three MMSE items across only two delayed recall trials demonstrated a sensitivity of 96.2% and specificity of 90.4% in differentiating between cases of dementia versus cases diagnosed with no cognitive impairment. The three trial delayed recall score enhanced prediction of mild cognitive impairment in at-risk elderly living with the community and may have promise in the development of future screening batteries.

Depressive symptoms in Alzheimer's disease. An examination among community-dwelling Cuban American patients.

The authors examined the prevalence and clinical correlates of mood disturbance in 96 Cuban American (CA) Alzheimer's disease (AD) patients. Depression (Cornell Scale for Depression in Dementia score > or = 7) was evident in 39.6% of the participants and showed associations with comorbid psychosis, lower education, and decreased length of residence in the United States, a measure of acculturation. Mood disturbance was not related to age, gender, marital status, cognitive dysfunction, functional impairment, history of significant alcohol use, or coexisting medical conditions. The results of this investigation suggest that signs and symptoms of depression are common neuropsychiatric disturbances in CA AD patients residing in the community.

Association between premorbid history of depression and current depression in Alzheimer's disease.

The relationship between a premorbid history of depression and the depressive syndrome in Alzheimer's disease (AD) remains equivocal. In the current study, we compared the prevalence of depression among patients with and without a history of mood disturbance prior to the onset of dementia. The sample comprised 243 AD outpatients evaluated consecutively at a university-affiliated memory disorders center. The results indicated that a positive history of depression was more common among patients with current depression compared to those without current depression (23% vs 11%, Fisher's Exact Test, P = .03). This relationship remained significant after controlling for the effects of age, education, gender, ethnicity, and level of cognitive impairment (odds ratio = 2.6, 95% confidence interval = 1.01-6.61, P = .04). Neither gender nor the interaction of gender and history of depression was shown to confer risk for current depressive symptoms. The present investigation suggests that premorbid depression may alter the risk for mood disturbance in AD.

Sensitivity and specificity of three clinical criteria for dementia with Lewy bodies in an autopsy-verified sample.

OBJECTIVE: To evaluate the sensitivity and specificity of the clinical features of three published diagnostic criteria for diffuse Lewy body disease (DLBD) using autopsy-confirmed Alzheimer's (AD), DLBD and AD+DLBD (mixed) dementia cases. DESIGN: Retrospective chart review of an autopsy series of 56 patients selected from the State of Florida Brain Bank on the basis of a pathological diagnosis of either pure AD, DLBD (pure and common forms) or AD+DLBD (mixed) dementia. Clinical features were assessed by three raters blind to the pathological diagnosis. RESULTS: The existing criteria for a clinical diagnosis of DLBD were highly specific (90-100%) but not very sensitive (49-63%) in the differential diagnosis of DLBD versus AD; sensitivity did improve (61-74%) when mixed AD+DLBD cases were eliminated. Clinical features that occur more frequently in DLBD than in AD were unspecified hallucinations, unspecified EPS, fluctuating course and rapid progression. Post-hoc analysis also indicated that hallucinations and EPS were more common early in the disease course of DLBD than in AD. Empirically derived criteria, formulated using the most prevalent clinical features, demonstrated sensitivity values of 57-96% for pure forms and 43-91% for mixed forms. CONCLUSIONS: This study demonstrated that additional improvements in the established criteria for DLBD are needed. Our empirically derived criteria enhanced the distinction of DLBD from AD while allowing the clinician the choice of maximizing sensitivity with acceptable specificity, and vice versa.

Factors associated with depressive symptoms in non-demented community-dwelling elderly.

OBJECTIVE: We examined the risk for depressive symptoms associated with age, education, ethnicity, gender, marital status, apolipoprotein E genotype (APOE) and memory complaints among non-demented elderly (> or = 60 years). DESIGN: Cross-sectional study of geriatric patients recruited from a free memory screening offered to the community. SAMPLE: This investigation included 506 community-residing elderly subjects who were screened for cognitive impairment and classified as non-demented based on age and education-adjusted Folstein Mini-Mental State Exam (MMSAdj) scores of 24 or greater. RESULTS: The prevalence of significant depressive symptoms (Hamilton Depression Rating Scale > or = 12) was 12.1% (N = 61). Increased risk for depression was associated with female gender (OR = 2.3; 95% CI = 1.1-4.8; p < 0.05), Cuban American ethnicity (OR = 4.9; 95% CI = 2.3-10.4; p < 0.0001) and memory complaints (OR = 1.3; 95% CI = 1.2-1.4; p < 0.0001). The APOE allele frequencies in the current sample were 0.07, 0.80 and 0.13 for the epsilon 2, epsilon 3 and epsilon 4 alleles, respectively. CONCLUSIONS: The results suggest that signs and symptoms of depression are common among non-demented elderly subjects in the community. In this study, mood disturbances were associated with Cuban American ethnicity, female gender and more memory complaints. Factors that were not confirmed by this study include age, education, marital status and APOE genotype. The observed APOE, epsilon 4 allele frequency of 0.13 supports the normal cognitive classification of the sample.

Prevalence and correlates of Capgras syndrome in Alzheimer's disease.

OBJECTIVES: This study examined the prevalence and clinical correlates of Capgras syndrome (CS) in Alzheimer's disease. DESIGN: Cross-sectional study of elderly patients evaluated at an outpatient memory disorders clinic classified according to the presence or absence of CS. SUBJECTS: One hundred and fifty-one consecutive patients diagnosed with probable (N=110) or possible (N=48) Alzheimer's disease (AD) utilizing NINCDS-ADRDA diagnostic criteria. MATERIALS: The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Mini-Mental State Examination (MMSE) and Blessed Dementia Scale (BDS). RESULTS: CS was observed in 10% of the sample (N=16). Associated factors included other delusions, lower MMSE scores and higher BDS scores. The relation between CS and both cognitive and functional status remained significant after controlling for other delusions. CONCLUSION: CS was prevalent in approximately 10% of our community-dwelling AD sample. This syndrome was more common at the later stages of the illness and showed relations with increased functional impairment and other psychotic symptomatology.

Apolipoprotein-E (APO-E) genotype and symptoms of psychosis in Alzheimer's disease.

The authors examined the association of Apolipoprotein-E (APO-E) genotype to symptoms of psychosis and depression in 501 patients diagnosed with probable (n=343) or possible (n=158) Alzheimer's disease (AD) according to NINCDS-ADRDA criteria. They observed the following APO-E genotypes: epsilon2/epsilon3 (n=19); epsilon2/epsilon4 (n=14); epsilon3/epsilon3 (n=228); epsilon3/epsilon4 (n=203); epsilon4/epsilon4 (n=37). In contrast to previous reports, the results did not indicate a relationship between either the epsilon4 allele or the epsilon2 allele and symptoms of mood disturbance in AD. However, an elevated risk for psychosis was shown, specifically, at the severe stage of cognitive impairment, among AD patients carrying the epsilon4 allele, after effects of age, gender, education, and level of cognitive impairment were controlled.

Biological impact on mineral dissolution: application of the lichen model to understanding mineral weathering in the rhizosphere.

Microorganisms modify rates and mechanisms of chemical and physical weathering and clay growth, thus playing fundamental roles in soil and sediment formation. Because processes in soils are inherently complex and difficult to study, we employ a model based on the lichen-mineral system to identify the fundamental interactions. Fixed carbon released by the photosynthetic symbiont stimulates growth of fungi and other microorganisms. These microorganisms directly or indirectly induce mineral disaggregation, hydration, dissolution, and secondary mineral formation. Model polysaccharides were used to investigate direct mediation of mineral surface reactions by extracellular polymers. Polysaccharides can suppress or enhance rates of chemical weathering by up to three orders of magnitude, depending on the pH, mineral surface structure and composition, and organic functional groups. Mg, Mn, Fe, Al, and Si are redistributed into clays that strongly adsorb ions. Microbes contribute to dissolution of insoluble secondary phosphates, possibly via release of organic acids. These reactions significantly impact soil fertility. Below fungi-mineral interfaces, mineral surfaces are exposed to dissolved metabolic byproducts. Through this indirect process, microorganisms can accelerate mineral dissolution, leading to enhanced porosity and permeability and colonization by microbial communities.

A cross-ethnic analysis of risk factors for AD in white Hispanics and white non-Hispanics.

BACKGROUND: The prevalence of AD appears to vary widely in different ethnic groups. Certain risk factors for AD are well established for the general population, but there is little information regarding the relevance of these risk factors in specific ethnic groups. OBJECTIVE: The authors examined the risk of AD associated with the APOE-epsilon4 allele, the APOE-epsilon2 allele, smoking, alcohol consumption, history of hypertension, low educational level, estrogen replacement therapy, and history of head trauma with loss of consciousness among samples of white non-Hispanics (WNH) (392 AD patients, 202 normal subjects) and white Hispanics (WHIS) (188 AD patients, 84 normal controls). DESIGN: This was a case-control study of patients evaluated at an outpatient memory disorders clinic and control subjects recruited from a free memory screening offered to the community. RESULTS: Increased risk for AD was associated with the APOE-epsilon4 allele after controlling for age, education, and gender among WNH (OR = 3.5; 95% CI = 2.3 to 5.5) and WHIS (OR = 3.1; 95% CI = 1.7 to 5.8). No protective effect was conferred by the APOE-epsilon2 allele, although this relationship approached significance among WNH (p = 0.02). Low levels of education increased the risk for AD among WNH (OR = 3.1; 95% CI = 1.8 to 5.9) but not WHIS. Alcohol use and hypertension approached significance as risk factors in WNH (p < 0.05) but not WHIS. Estrogen replacement treatment approached significance as a protective factor in both ethnic groups (p < 0.05). CONCLUSIONS: Although the APOE-epsilon4 allele is a risk factor for AD among WHIS and WNH, other risk factors such as low education and hypertension appear to be important only for WNH. Risk factors for AD reported or suggested previously that were not confirmed by this study include smoking and head trauma with loss of consciousness.

The behavioral pathology in Alzheimer's Disease Scale (BEHAVE-AD): factor structure among community-dwelling Alzheimer's disease patients.

OBJECTIVE: The aims of this study were to (a) determine the factor structure of the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD), and (b) examine the associations of the observed factors to the level of cognitive impairment. DESIGN: Cross-sectional study of geriatric patients evaluated at an outpatient memory disorders clinic. SAMPLE: One hundred and fifty-one consecutive patients diagnosed with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria. RESULTS: Principal factors analysis with Varimax rotation resulted in a five-factor solution that accounted for 40.0% of the common variance. The factors included agitation/anxiety (agitation, anxiety of upcoming events; other anxiety), psychosis (delusions of theft, suspiciousness/paranoia; visual hallucinations), aggression (verbal aggressiveness; physical threats/violence; fear of being left alone; other delusions), depression (tearfulness; depressed mood) and activity disturbance (wandering; delusion one's house is not one's home). Several factors were associated with level of cognitive impairment as assessed by the Mini-Mental State Examination (MMSE). CONCLUSION: The results of this study suggest that the BEHAVE-AD measures a wide range of behavioral pathology that can be empirically represented by five independent symptom clusters among outpatient AD patients.