Plasma Alzheimer's biomarkers and brain amyloid in Hispanic and non-Hispanic older adults.

INTRODUCTION: Alzheimer's disease studies often lack ethnic diversity. METHODS: We evaluated associations between plasma biomarkers commonly studied in Alzheimer's (p-tau181, GFAP, and NfL), clinical diagnosis (clinically normal, amnestic MCI, amnestic dementia, or non-amnestic MCI/dementia), and Aß-PET in Hispanic and non-Hispanic older adults. Hispanics were predominantly of Cuban or South American ancestry. RESULTS: Three-hundred seventy nine participants underwent blood draw (71.9 ± 7.8 years old, 60.2% female, 57% Hispanic of which 88% were Cuban or South American) and 240 completed Aß-PET. P-tau181 was higher in amnestic MCI (p = 0.004, d = 0.53) and dementia (p < 0.001, d = 0.97) than in clinically normal participants and discriminated Aß-PET[+] and Aß-PET[-] (AUC = 0.86). P-tau181 outperformed GFAP and NfL. There were no significant interactions with ethnicity. Among amnestic MCI, Hispanics had lower odds of elevated p-tau181 than non-Hispanic (OR = 0.41, p = 0.006). DISCUSSION: Plasma p-tau181 informs etiological diagnosis of cognitively impaired Hispanic and non-Hispanic older adults. Hispanic ethnicity may relate to greater likelihood of non-Alzheimer's contributions to memory loss. HIGHLIGHTS: Alzheimer's biomarkers were measured in Hispanic and non-Hispanic older adults. Plasma p-tau181 related to amnestic cognitive decline and brain amyloid burden. AD biomarker associations did not differ between Hispanic and non-Hispanic ethnicity. Hispanic individuals may be more likely to have non-Alzheimer causes of memory loss.

A Novel Cognitive Stress Test for the Detection of Preclinical Alzheimer Disease: Discriminative Properties and Relation to Amyloid Load.

OBJECTIVE: To examine the utility of a novel "cognitive stress test" to detect subtle cognitive impairments and amyloid load within the brains of neuropsychologically normal community-dwelling elders. METHODS: Participants diagnosed as cognitively normal (CN), subjective memory impairment (SMI), mild cognitive impairment (MCI), and preclinical mild cognitive impairment (PreMCI) were administered the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), a sensitive test of proactive semantic interference (PSI), retroactive semantic interference, and, uniquely, the ability to recover from the effects of PSI. Ninety-three subjects (31 men and 62 women) were recruited from three academic institutions in a research consortium. A subset of these individuals underwent 18F florbetapir positron emission tomography scanning. Relative percentages of impairment for each diagnostic group on the LASSI-L were calculated by χ(2) and Fisher's exact tests. Spearman's rho was used to examine associations between amyloid load and different cognitive measures. RESULTS: LASSI-L deficits were identified among 89% of those with MCI, 47% with PreMCI, 33% with SMI, and 13% classified as CN. CN subjects had no difficulties with recovery from PSI, whereas SMI, preMCI, and MCI participants evidenced deficits in recovery from PSI effects. Among a subgroup of participants with normal scores on traditional neuropsychological tests, the strong associations were between the failure to recover from the effects of PSI and amyloid load in the brain. CONCLUSION: Failure to recover or compensate for the effects of PSI on the LASSI-L distinguishes the LASSI-L from other widely used neuropsychological tests and appears to be sensitive to subtle cognitive impairments and increasing amyloid load.

Proactive Semantic Interference is Associated with Total and Regional Abnormal Amyloid Load in Non-Demented Community-Dwelling Elders: A Preliminary Study.

OBJECTIVE: To evaluate the relationship between susceptibility to proactive semantic interference (PSI) and retroactive semantic interference (RSI) and brain amyloid load in non-demented elders. METHODS: 27 participants (11 cognitively normal [CN] with subjective memory complaints, 8 CN without memory complaints, and 8 with mild cognitive impairment [MCI]) underwent complete neurological and neuropsychological evaluations. Participants also received the Semantic Interference Test (SIT) and AV-45 amyloid PET imaging. RESULTS: High levels of association were present between total amyloid load, regional amyloid levels, and the PSI measure (in the entire sample and a subsample excluding MCI subjects). RSI and other memory measures showed much weaker associations or no associations with total and regional amyloid load. No associations between amyloid levels and non-memory performance were observed. CONCLUSIONS: In non-demented individuals, vulnerability to PSI was highly associated with total and regional beta-amyloid load and may be an early cognitive marker of brain pathology.

Cross-cultural Diagnostic Validity of the Multilingual Naming Test (MINT) in a Sample of Older Adults.

OBJECTIVE: We aimed to evaluate the psychometric properties and diagnostic accuracy of the 32-item version of the Multilingual Naming Test (MINT) in participants from 2 ethnic groups (European Americans [EA; n = 106] and Hispanic Americans [HA; n = 175]) with 3 diagnostic groups (cognitively normal [CN], n = 94, mild cognitive impairment [MCI], n = 148, and dementia, n = 39). METHOD: An Item Response Theory model was used to evaluate items across ethnicity and language groups (Spanish and English), resulting in a 24-item version. We analyzed the MINT discriminant and predictive validity across diagnostic groups. RESULTS: A total of 8 items were differentially difficult between languages in the 32-item version of the MINT. EA scored significantly higher than HA, but the difference was not significant when removing those 8 items (controlling for Education). The Receiver Operating Characteristics showed that the MINT had poor accuracy when identifying CN participants and was acceptable in identifying dementia participants but unacceptable in classifying MCI participants. Finally, we tested the association between MINT scores and magnetic resonance imaging volumetric measures of language-related areas in the temporal and frontal lobes. The 32-item MINT in English and Spanish and the 24-item MINT in Spanish were significantly correlated with the bilateral middle temporal gyrus. The left fusiform gyrus correlated with MINT scores regardless of language and MINT version. We also found differential correlations depending on the language of administration. CONCLUSIONS: Our results highlight the importance of analyzing cross-cultural samples when implementing clinical neuropsychological tests such as the MINT.

Stability in cognitive classification as a function of severity of impairment and ethnicity: A longitudinal analysis.

OBJECTIVE: The interaction of ethnicity, progression of cognitive impairment, and neuroimaging biomarkers of Alzheimer's Disease remains unclear. We investigated the stability in cognitive status classification (cognitively normal [CN] and mild cognitive impairment [MCI]) of 209 participants (124 Hispanics/Latinos and 85 European Americans). METHODS: Biomarkers (structural MRI and amyloid PET scans) were compared between Hispanic/Latino and European American individuals who presented a change in cognitive diagnosis during the second or third follow-up and those who remained stable over time. RESULTS: There were no significant differences in biomarkers between ethnic groups in any of the diagnostic categories. The frequency of CN and MCI participants who were progressors (progressed to a more severe cognitive diagnosis at follow-up) and non-progressors (either stable through follow-ups or unstable [progressed but later reverted to a diagnosis of CN]) did not significantly differ across ethnic groups. Progressors had greater atrophy in the hippocampus (HP) and entorhinal cortex (ERC) at baseline compared to unstable non-progressors (reverters) for both ethnic groups, and more significant ERC atrophy was observed among progressors of the Hispanic/Latino group. For European Americans diagnosed with MCI, there were 60% more progressors than reverters (reverted from MCI to CN), while among Hispanics/Latinos with MCI, there were 7% more reverters than progressors. Binomial logistic regressions predicting progression, including brain biomarkers, MMSE, and ethnicity, demonstrated that only MMSE was a predictor for CN participants at baseline. However, for MCI participants at baseline, HP atrophy, ERC atrophy, and MMSE predicted progression.

Semantic intrusion errors are associated with plasma Ptau-181 among persons with amnestic mild cognitive impairment who are amyloid positive.

Introduction: Semantic intrusion errors (SI) have distinguished between those with amnestic Mild Cognitive Impairment (aMCI) who are amyloid positive (A+) versus negative (A-) on positron emission tomography (PET). Method: This study examines the association between SI and plasma - based biomarkers. One hundred and twenty-eight participants received SiMoA derived measures of plasma pTau-181, ratio of two amyloid-ß peptide fragments (Aß42/Aß40), Neurofilament Light protein (NfL), Glial Fibrillary Acidic Protein (GFAP), ApoE genotyping, and amyloid PET imaging. Results: The aMCI A+ (n = 42) group had a higher percentage of ApoE ɛ4 carriers, and greater levels of pTau-181 and SI, than Cognitively Unimpaired (CU) A- participants (n = 25). CU controls did not differ from aMCI A- (n = 61) on plasma biomarkers or ApoE genotype. Logistic regression indicated that ApoE ɛ4 positivity, pTau-181, and SI were independent differentiating predictors (Correct classification = 82.0%; Sensitivity = 71.4%; Specificity = 90.2%) in identifying A+ from A- aMCI cases. Discussion: A combination of plasma biomarkers, ApoE positivity and SI had high specificity in identifying A+ from A- aMCI cases.

Patient values in healthcare decision making among diverse older adults.

OBJECTIVE: To provide high-quality healthcare, it is essential to understand values that guide the healthcare decisions of older adults. We investigated the types of values that culturally diverse older adults incorporate in medical decision making. METHODS: Focus groups were held with older adults who varied in cognitive status (mildly impaired versus those with normal cognition) and ethnicity (Hispanic and non-Hispanic). Investigators used a qualitative descriptive approach to analyze transcripts and identify themes. RESULTS: Forty-nine individuals (49% with cognitive impairment; 51% Hispanic) participated. Participants expressed a wide range of values relating to individual factors, familial/cultural beliefs and expectations, balancing risks and benefits, receiving decisional support, and considering values other than their own. Participants emphasized that values are individual-specific, influenced by aging, and change throughout life course. Participants described barriers and facilitators that interfere with or promote value solicitation and incorporation during medical encounters. CONCLUSION: Study findings highlight that in older adults with various health experiences, cognitive and physical health status, and sociocultural backgrounds, medical decisions are influenced by a variety of values. PRACTICAL IMPLICATIONS: Clinicians should take time to elicit, understand, and reassess the different types of values of older adults.

The association of depression and apathy with Alzheimer's disease biomarkers in a cross-cultural sample.

Cross-cultural differences in the association between neuropsychiatric symptoms and Alzheimer's disease (AD) biomarkers are not well understood. This study aimed to (1) compare depressive symptoms and frequency of reported apathy across diagnostic groups of participants with normal cognition (CN), mild cognitive impairment (MCI), and dementia, as well as ethnic groups of Hispanic Americans (HA) and European Americans (EA); (2) evaluate the relationship between depression and apathy with Aß deposition and brain atrophy. Statistical analyses included ANCOVAs, chi-squared, nonparametric tests, correlations, and logistic regressions. Higher scores on the Geriatric Depression Scale (GDS-15) were reported in the MCI and dementia cohorts, while older age corresponded with lower GDS-15 scores. The frequency of apathy differed across diagnoses within each ethnicity, but not when comparing ethnic groups. Reduced volume in the rostral anterior cingulate cortex (ACC) significantly correlated with and predicted apathy for the total sample after applying false discovery rate corrections (FDR), controlling for covariates. The EA group separately demonstrated a significant negative relationship between apathy and superior frontal volume, while for HA, there was a relationship between rostral ACC volume and apathy. Apathy corresponded with higher Aß levels for the total sample and for the CN and HA groups.

Depression and the Diagnosis of MCI in a Culturally Diverse Sample in the United States.

OBJECTIVE: To analyze (1) whether there are ethnic differences in the severity of depressive symptoms between groups of elders classified as cognitively normal (CN) or amnestic mild cognitive impairment (aMCI) and (2) the influence of depressive symptoms on specific cognitive performance by ethnicity across diagnoses, controlling for covariates. METHODS: 164 Hispanics residing in the United States (HAs) and European Americans (EAs) (100 women; Mage = 72.1, SD = 8.0) were diagnosed as either CN or aMCI. Depressive symptoms were measured with the Geriatric Depression Scale (GDS-15). Cognition was assessed using the Loewenstein-Acevedo Scales for Semantic Interference and Learning (semantic memory), Multilingual Naming Test (confrontation naming), and the Stroop Test (Color-Word condition; executive function). A 2 × 2 univariate ANCOVA as well as linear and logistic regressions explored differences in depressive symptoms among diagnostic and ethnic groups. RESULTS: Higher depression was seen in aMCI compared to the CN group for both ethnicities, after controlling for age, education, gender, and Mini-Mental State Examination score. Greater levels of depression also predicted lower scores in confrontation naming and semantic memory for only the EA group and marginally in scores of executive function for HA participants. GDS-15 scores of ≤ 4 also predicted less likelihood of aMCI diagnosis. CONCLUSIONS: Severity of depressive symptoms was associated with greater cognitive impairment, independent of ethnicity. Significant results suggest detrimental effects of depression on clinical diagnoses most evidently for subjects from the EA group.

The Association Between Functional Assessment and Structural Brain Biomarkers in an Ethnically Diverse Sample With Normal Cognition, Mild Cognitive Impairment, or Dementia.

OBJECTIVE: To investigate the association between the functional activities questionnaire (FAQ) and brain biomarkers (bilateral hippocampal volume [HV], bilateral entorhinal volume [ERV], and entorhinal cortical thickness [ERT]) in cognitively normal (CN) individuals, mild cognitive impairment (MCI), or dementia. METHOD: In total, 226 participants (137 females; mean age = 71.76, SD = 7.93; Hispanic Americans = 137; European Americans = 89) were assessed with a comprehensive clinical examination, a neuropsychological battery, a structural magnetic resonance imaging, and were classified as CN or diagnosed with MCI or dementia. Linear regression analyses examined the association between functional activities as measured by the FAQ on brain biomarkers, including HV, ERV, and ERT, controlling for age, education, global cognition, gender, and ethnicity. RESULTS: The FAQ significantly predicted HV, ERV, and ERT for the entire sample. However, this association was not significant for ERV and ERT when excluding the dementia group. The FAQ score remained a significant predictor of HV for the non-dementia group. Age, education, gender, ethnicity, Montreal Cognitive Assessment score, and FAQ were also significant predictors of HV for the overall sample, suggesting that younger Hispanic females with fewer years of education, higher global mental status, and better functioning, were more likely to have larger HV. CONCLUSION: FAQ scores were related to HV in older adults across clinical groups (CN, MCI, and dementia), but its association with the entorhinal cortex was driven by individuals with dementia. Demographic variables, including ethnicity, additionally influenced these associations.

Changes in LASSI-L performance over time among older adults with amnestic MCI and amyloid positivity: A preliminary study.

There is a pressing need to develop measures that are sensitive to the earliest subtle cognitive changes of Alzheimer's disease (AD) to improve early detection and track disease progression. The Loewenstein-Acevedo Scales of Semantic Interference (LASSI-L) has been shown to successfully discriminate between cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (MCI) and to correlate with total and regional brain amyloid load. The present study investigated how the LASSI-L scores change over time among three distinct diagnostic groups. Eighty-six community-dwelling older adults underwent a baseline evaluation including: a clinical interview, a neuropsychological evaluation, Magnetic Resonance Imaging (MRI), and amyloid Positron Emission Tomography (PET). A follow up evaluation was conducted 12 months later. Initial mean values were calculated using one-way ANOVAs and chi-square analyses. Post-hoc comparisons were conducted using Tukey's Honestly Significant Difference (HSD). A 3 × 2 repeated measures analysis was utilized to examine differences in LASSI-L performance over time. The MCI amyloid positive group demonstrated a significantly greater decline in LASSI-L performance than the MCI amyloid negative and CU groups respectively. The scales that best differentiated the three groups included the Cued A2, which taps into maximum learning capacity, and Cued B2, which assesses the failure to recover from proactive semantic interference. Our findings further support the LASSI-L's discriminative validity.

The effect of alcohol and tobacco consumption, and apolipoprotein E genotype, on the age of onset in Alzheimer's disease.

OBJECTIVE: This study examined the association between a history of heavy alcohol use and smoking, presence of the apolipoprotein-E epsilon 4 allele (APOE epsilon4), and age of disease onset in a community dwelling sample of 685 Alzheimer's disease (AD) patients spanning three ethnic groups. DESIGN: Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic. SUBJECTS: A clinic-based cohort of white non-Hispanic (WNH; n = 397), white Hispanic (WH; n = 264), and African-American (AA; n = 24) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria. MEASUREMENTS: The age of onset of AD was obtained from a knowledgeable family member. All patients were assessed for APOE genotype. History of alcohol and tobacco consumption prior to the onset of dementia was obtained via an interview with the patient and the primary caregiver. A history of heavy drinking was defined as >2 drinks per day and a history of heavy smoking was defined as > or =1 pack per day. RESULTS: Presence of an APOE epsilon4 allele, a history of heavy drinking, or a history of heavy smoking were each associated with an earlier onset of AD by 2-3 years. Patients with all three risk factors were likely to be diagnosed with AD nearly 10 years earlier than those with none of the risk factors. CONCLUSION: The results suggest that APOE epsilon4 and heavy drinking and heavy smoking lower the age of onset for AD in an additive fashion.

Severity of medial temporal atrophy and amnestic mild cognitive impairment: selecting type and number of memory tests.

OBJECTIVE: Medial temporal lobe atrophy (MTA) can be used as a biomarker of pathology that affects mechanisms of episodic memory. The authors compared the strength of this biomarker with performance on four memory measures and examined the influence of demographic factors including age, level of education, and primary language (English or Spanish). METHODS: The Hopkins Verbal Learning Test-revised, Fuld Object Memory Evaluation (FOME), delayed memory for a story passage, and delayed visual reproduction of the Wechsler Memory Scale-revised tests were administered to 281 subjects who were diagnosed as having no cognitive impairment, mild cognitive impairment (MCI), impaired non-MCI, or dementia. MTA scores were obtained from visual ratings of the hippocampus, entorhinal cortex, and perirhinal cortex on coronal magnetic resonance imaging scans using a magnetization-prepared rapid gradient echo protocol. RESULTS: Age was associated with scores on all memory measures and MTA. Level of educational attainment had no influence on FOME performance but had greater associations with scores on other memory measures. In regression models, FOME scores had the strongest relationship with MTA scores, accounting for 31% of the explained variability. Among subjects with MCI, an index representing the total number of memory tests that were impaired was also predictive of the severity of MTA scores. CONCLUSION: Among four common tests of memory, the FOME was highly associated with MTA, and it exhibited minimal influences of education. Impairment on more than one memory test was more predictive of MTA than impairment on a single memory test.

Patterns of depression in Spanish- and English-speaking patients with Alzheimer's disease.

The purpose of this study was to evaluate whether distinct subtypes of depression could be identified in patients with Alzheimer's disease and, if so, to evaluate the patients in these subgroups. Ratings on the Cornell Scale for Depression in Dementia (CSDD) of 306 patients with Alzheimer's disease, 129 of whom were Spanish- and 177 English-speaking, were subjected to latent class analysis. Four subgroups were identified based on CSDD symptoms. These included an asymptomatic group, groups with mild and more severe typical depression, and a group characterized by prominent anxiety and irritability in addition to sadness. Group differences on demographic, cognitive, clinical, and functional status measures were explored via chi-square tests and analyses of variance. Results show that for some patients with Alzheimer's disease, patterns of symptoms of depression are similar to those in younger adult populations. A distinct subtype may exist, however, with prominent anxiety and irritability.

The cyclooxygenase 2 -765 C promoter allele is a protective factor for Alzheimer's disease.

The cyclooxygenase-2 enzyme (COX-2) is of particular importance in the inflammatory response and recent findings have demonstrated a considerable role in Alzheimer's disease (AD) pathogenesis. In order to assess the possible putative role of a COX-2 polymorphism (765G/C) in AD, we examined its distribution in 161 community-based controls and 168 AD clinic-based cases previously recruited from memory disorder clinics in Tampa and Miami, Florida. There were no significant differences between the two groups in age/age of onset or gender. A significant difference was observed in the distribution of the COX-2 -765 alleles between AD cases and controls (chi(2) = 6.565, p = .010; OR = .596; CI = [.401-.888], p = .011), with the frequency of the C allele being higher in controls. In addition, a significant difference was observed for this polymorphism by genotype (chi(2) = 6.561, p = .038) and by presence or absence of C+ genotypes (chi(2) = 6.207, p = .013; OR = .464, CI = [.351-.885], p = .013). In this sample, the C allele of COX-2 -765 promoter polymorphism is associated with decreased risk of Alzheimer's disease, a finding which further supports the involvement of COX-2 in AD etiology.

A clinical perspective of mild cognitive impairment: what radiologists should know.

Mild cognitive impairment (MCI), a major risk factor for dementia, has an amnestic subtype that has a high probability of progressing to Alzheimer's disease. The rate of progression may be predicted by the severity of memory impairment at baseline, the severity of hippocampal atrophy, and, possibly, the presence of an epsilon4 allele of the apolipoprotein E gene. MCI can be diagnosed using purely clinical or a combination of clinical and neuropsychologic criteria. Treatment trials show no disease-modifying effect. The radiologists' role is to determine whether or not the hallmarks of degenerative and vascular disease of the brain are present, aiding in the diagnosis of the cause of MCI.

Using different memory cutoffs to assess mild cognitive impairment.

OBJECTIVE: Although mild cognitive impairment (MCI) is characterized by performance on memory and other measures below expected normative values, neither a scientific rationale nor a consensus exists regarding which measures have the most use or the optimal cutoffs to use to establish impairment. METHODS: Different memory measures were administered to 80 normal community-dwelling subjects divided into two age groups. This provided conormed data on eight different memory indices by which to compare 23 nondemented clinically diagnosed patients with MCI who met all other criteria for Alzheimer disease (AD). RESULTS: On immediate memory for passages, delayed visual reproduction, object memory, and a measure sensitive to semantic interference, 70%-78% of patients with MCI were identified as impaired at 1.5 standard deviations or greater below expected levels. Conditional logistical regression for age-matched samples indicated that consideration of raw scores for these neuropsychologic tests in combination did not significantly change the odds of MCI diagnosis. When impairment relative to the total normal elderly sample was calculated based on one or more impairments at a 1.5 or greater cutoff, specificity fell below acceptable levels when more than three memory measures were considered. CONCLUSION: An array of widely used neuropsychologic measures demonstrated utility in distinguishing patients with MCI-AD from cognitively normal community-dwelling elders. The appropriateness of more or less stringent cutoffs was highly influenced by the number of measures considered. These findings have important implications regarding the choice of cut points for impairment used for the diagnosis of MCI in both research and clinical settings.

Cognitive profiles in Alzheimer's disease and in mild cognitive impairment of different etiologies.

There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer's disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed.

The effect of a memory screening program on the early diagnosis of Alzheimer disease.

CONTEXT: Alzheimer Disease (AD) is often diagnosed at a moderately advanced stage, even though its early detection has become increasingly important, because of the continuing development of treatments that may improve its outcome. OBJECTIVE: To determine if a free memory screening program is associated with an earlier diagnosis of AD, compared with traditional referral methods, such as by physicians and family members. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of 1489 consecutive patients with AD who presented to an outpatient memory disorders clinic between 1993 and 2002. Subjects were classified according to referral source (memory screening, physician, family/friend, other), and self-reported ethnicity (white non-Hispanic, white Hispanic). The associations between referral source and the presenting cognitive and behavioral status of subjects were evaluated using analysis of variance and logistic regression analyses, after controlling for potentially confounding factors. MAIN OUTCOME MEASURES: Score on the Folstein Mini-Mental State Examination (MMSE), duration of cognitive symptoms, and presence of psychosis, defined as delusions and/or hallucinations. RESULTS: After controlling for ethnicity, gender, and the year of diagnosis, subjects with AD, who were referred by the memory screening program, scored significantly higher at presentation on the MMSE (20.8 +/- 5.7), than those referred by physicians (18.8 +/- 6.6), family/friends (16.8 +/- 6.6), or other referral sources (15.3 +/- 7.1). Subjects with AD, referred by the memory screening program, also had a lower reported duration of illness at presentation, and a decreased frequency of psychosis compared with those referred by family/friend and other methods. Other factors related to a diagnosis of AD at a later stage included female gender, Hispanic ethnicity, and a diagnosis early in the 1993 to 2002 time period. CONCLUSIONS: The memory screening program referred patients with AD to a memory clinic at an earlier phase of illness compared with traditional methods such as physician referral.

No association between subjective memory complaints and apolipoprotein E genotype in cognitively intact elderly.

OBJECTIVE: This cross-sectional study examined the relationship between subjective memory complaints and the apolipoprotein epsilon 4 allele (epsilon4), a genetic risk factor for Alzheimer's disease (AD), among cognitively normal subjects identified from a community memory screening. DESIGN: The sample comprised 232 consecutive white non-Hispanic older adults who presented to a free community-based memory-screening program at a University affiliated memory disorders center. Participants were classified as cognitively normal based on scores on the age and educated adjusted Folstein Mini-Mental Status Exam (MMSAdj) and a brief Delayed Verbal Recall Test (DRT). Subjects were assessed for APOE genotype, subjective memory complaints (Memory Questionnaire, MQ), depressive symptoms (Hamilton Depression Rating Scale, HDRS), and history of four major medical conditions that have been associated with memory loss (stroke/transient ischemic attack [TIA], atherosclerotic heart disease, hypertension, and diabetes). A hierarchical regression analysis was performed to examine the association between APOE genotype and memory complaints after controlling for a host of potential confounding factors. RESULTS: The APOE epsilon4 allele frequency for cognitively normal subjects was 0.13. Subjective memory complaints were predicted by depressive symptoms and a history of stroke/TIA. They were not associated with APOE genotype, MMSAdj score, DRT score, age, education, gender, and reported history of atherosclerotic heart disease, hypertension, or diabetes. CONCLUSION: The results did not suggest an association between subjective memory complaints and the APOE epsilon4 allele in this sample of cognitively intact subjects. This indicates that memory complaints may confer risk for future dementia through pathways independent of APOE genotype. The results also show that older adults with memory complaints are at increased risk for underlying depression.