The relationship between obsessive-compulsive symptoms and PARKIN genotype: The CORE-PD study.

BACKGROUND: Few studies have systematically investigated the association between PARKIN genotype and psychiatric co-morbidities of Parkison's disease (PD). PARKIN-associated PD is characterized by severe nigral dopaminergic neuronal loss, a finding that may have implications for behaviors rooted in dopaminergic circuits such as obsessive-compulsive symptoms (OCS). METHODS: The Schedule of Compulsions and Obsessions Patient Inventory (SCOPI) was administered to 104 patients with early-onset PD and 257 asymptomatic first-degree relatives. Carriers of one and two PARKIN mutations were compared with noncarriers. RESULTS: Among patients, carriers scored lower than noncarriers in adjusted models (one-mutation: 13.9 point difference, P = 0.03; two-mutation: 24.1, P = 0.001), where lower scores indicate less OCS. Among asymptomatic relatives, a trend toward the opposite was seen: mutation carriers scored higher than noncarriers (one mutation, P = 0.05; two mutations, P = 0.13). CONCLUSIONS: First, a significant association was found between PARKIN mutation status and obsessive-compulsive symptom level in both PD and asymptomatic patients, suggesting that OCS might represent an early non-motor dopamine-dependent feature. Second, irrespective of disease status, heterozygotes were significantly different from noncarriers, suggesting that PARKIN heterozygosity may contribute to phenotype. © 2014 International Parkinson and Movement Disorder Society.

Interest in genetic testing in Ashkenazi Jewish Parkinson's disease patients and their unaffected relatives.

Our objective was to explore interest in genetic testing among Ashkenazi Jewish (AJ) Parkinson's Disease (PD) cases and first-degree relatives, as genetic testing for LRRK2 G2019S is widely available. Approximately 18 % of AJ PD cases carry G2019S mutations; penetrance estimations vary between 24 and 100 % by age 80. A Genetic Attitude Questionnaire (GAQ) was administered at two New York sites to PD families unaware of LRRK2 G2019S mutation status. The association of G2019S, age, education, gender and family history of PD with desire for genetic testing (outcome) was modeled using logistic regression. One-hundred eleven PD cases and 77 relatives completed the GAQ. Both PD cases and relatives had excellent PD-specific genetic knowledge. Among PD, 32.6 % "definitely" and 41.1 % "probably" wanted testing, if offered "now." Among relatives, 23.6 % "definitely" and 36.1 % "probably" wanted testing "now." Desire for testing in relatives increased incrementally based on hypothetical risk of PD. The most important reasons for testing in probands and relatives were: if it influenced medication response, identifying no mutation, and early prevention and treatment. In logistic regression, older age was associated with less desire for testing in probands OR = 0.921 95%CI 0.868-0.977, p = 0.009. Both probands and relatives express interest in genetic testing, despite no link to current treatment or prevention.

Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations.

The phenotype of Parkinson's disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel-Aviv). Glucocerebrosidase (GBA) mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinson's Disease Rating Scale (UPDRS), the Geriatric Depression Scale (GDS) and the Non-Motor Symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. LRRK2 G2019S carriers (n = 97) and non-carriers (n = 391) were similar in age and age at onset of PD. Carriers had longer disease duration (8.6 years vs. 6.1 years; P < 0.001), were more likely to be women (51.5% vs. 37.9%; P = 0.015), and more often reported first symptoms in the lower extremities (40.0% vs. 19.2%; P < 0.001). In logistic models that were adjusted for age, disease duration, sex, education, and site, carriers were more likely to have lower extremity onset (P < 0.001), postural instability and gait difficulty (PIGD) (P = 0.043), and a persistent levodopa response for >5 years (P = 0.042). Performance on the UPDRS, MoCA, GDS, and NMS did not differ by mutation status. PD in AJ LRRK2 G2019S mutation carriers is similar to idiopathic PD but is characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment.

Course and etiology of dysexecutive MCI in a community sample.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is associated with an elevated risk of progressing to Alzheimer's disease. Much less is known about the course of dysexecutive mild cognitive impairment (dMCI). The goals of this study were to determine how the profile of cognitive deficits differs over time between patients with dMCI and aMCI, and control subjects; if the type of dementia differs between dMCI and aMCI in patients who progress to dementia; and if dMCI is more associated with stroke and white matter hyperintensity on magnetic resonance imaging (MRI) than aMCI. METHODS: The authors undertook a prospective evaluation of an inception cohort of 1167 ethnically diverse elders recruited from an urban community-based sample monitored with clinical and neuropsychological testing for an average of 4.5 years (standard deviation, 0.8 year). A subset of the subjects underwent MRI. We compared four groups of MCI patients: single-domain amnestic and dysexecutive MCI, and multiple-domain MCI with and without executive dysfunction. RESULTS: Compared with aMCI, dMCI was less likely to involve other areas of cognition over time and progress to dementia. None of the 33 single-domain dMCI patients progressed to dementia. The presence of executive dysfunction in multiple-domain MCI did not increase risk of progression to dementia. Patients with multiple-domain MCI with executive dysfunction who progressed to dementia were less likely to have an Alzheimer's-type dementia than MCI patients without executive dysfunction. Patients with dMCI were more likely to experience stroke, but not white matter hyperintensity, detected via MRI than patients with aMCI. CONCLUSIONS: dMCI appears to follow a different course, and is less associated with Alzheimer's disease and more associated with stroke than aMCI.

Neuropsychological Profile of Parkin Mutation Carriers with and without Parkinson Disease: The CORE-PD Study.

The cognitive profile of early onset Parkinson's disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson's disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study.

Peripheral Abeta subspecies as risk biomarkers of Alzheimer's disease.

Plasma Abeta42 and Abeta40 levels are putative biomarkers for Alzheimer's disease (AD), but their significance and predictive value have been inconclusive. In AD transgenic models, plasma and cerebrospinal fluid levels of Abeta42 and Abeta40 increase with age but subsequently decrease when Abeta begins to accumulate in brain and with the onset of cognitive impairment. To determine the predictive value of Abeta levels in elderly populations, we investigated how plasma Abeta42, Abeta40, and a protofibrillar subspecies of Abeta42 changed over time and with the onset of cognitive impairment or AD. In a cohort of 1,125 elderly persons without dementia, 104 (9.2%) of the participants developed AD over 4.6 years of follow-up. Higher plasma Abeta42 levels at the onset of the study were associated with a threefold increased risk of AD. However, conversion to AD was accompanied by a significant decline in plasma Abeta42, a decreased Abeta42/Abeta40 ratio and, with the onset of cognitive impairment, decreased protofibrillar Abeta42 levels. Our results suggest individuals with elevated plasma Abeta42 are at increased risk of AD and that with the onset of disease, the decline in some forms of Abeta may reflect compartmentalization of Abeta peptides in the brain.

Mild parkinsonian signs are associated with increased risk of dementia in a prospective, population-based study of elders.

There is some evidence that mild parkinsonian signs (MPSs) are associated with increased risk of dementia, suggesting that MPS could be an early biomarker for dementia. Our aims, in a new cohort, were to determine whether (1) baseline MPS are a predictor of incident dementia and (2) there is an interaction between MPS and other baseline risk factors for dementia (i.e., the presence of both together greatly elevates the risk of dementia) was the objective. In a prospective, longitudinal study of community-dwelling elders in northern Manhattan, NY, Parkinsonian signs were rated with an abbreviated Unified Parkinson's Disease Rating Scale. Risk of incident dementia was assessed using Cox proportional hazards models. There were 1,851 participants (mean follow-up = 3.7 years). Participants with baseline MPS were twice as likely to develop dementia as participants without MPS: 16.3% versus 7.7%, unadjusted hazards ratio (HR) = 2.24 (P< 0.001), adjusted HR = 1.98 (P < 0.001). MPS were divided into three subtypes: adjusted HR(axial dysfunction) = 2.45 (P < 0.001), adjusted HR(tremor) = 2.38 (P = 0.006), and adjusted HR(rigidity) = 1.16 (P = 0.58). When MPS were treated as a continuous variable, the adjusted HR = 1.15 (P = 0.001). There were no interactions between MPS and other baseline risk factors for dementia, including gender, education, race, family history of dementia, stroke, and apolipoprotein E-e4. Baseline MPS seems to be a predictor of incident dementia. These motor signs might, therefore, serve as a useful biomarker for emerging dementia.

Frequency and course of mild cognitive impairment in a multiethnic community.

OBJECTIVE: To examine incidence rates and antecedents of mild cognitive impairment (MCI) and Alzheimer's disease (AD) among diverse elders without dementia at the initial visit, and to examine the characteristics of elders with MCI who reverted to normal on follow-up examination. METHODS: A total of 2,364 Caribbean Hispanic, black, or non-Hispanic white subjects, aged 65 or older, who were free of dementia at initial evaluation were followed up every 18 to 24 months. Incidence rate of MCI and AD was determined by examination of neurological, medical, psychiatric, and neuropsychological function. RESULTS: Over 10,517 person-years, 21% of normal elderly subjects progressed to MCI (annual incidence rate, 5.1%; 95% confidence interval, 4.6-5.6%). Of those with MCI initially, 21.8% were subsequently diagnosed with AD (annual incidence rate, 5.4%; 95% confidence interval, 4.7-6.3%), 47% remained unchanged, and 31% reverted to normal. Those with MCI were 2.8 times more likely to experience development of AD than normal elderly subjects. MCI with impairment in memory and at least one other cognitive domain was associated with greatest risk for progression to AD and was also least likely to revert to normal at follow-up. Consistent diagnosis of MCI or incident probable or possible AD was 60% sensitive and 94% specific for the pathological diagnosis of AD. INTERPRETATION: Impaired memory and language were useful predictors of transition to AD. Reversion to normal from MCI was frequent, but those with impairment in more than one cognitive domain were more likely to progress or remain impaired than those with single-domain impairment. Clinical diagnosis of MCI does not always predict AD neuropathology.

Motor unit number estimation (MUNE) in diseases of the motor neuron: utility and comparative analysis in a multimodal biomarker study.

We prospectively studied 64 patients with motor neuron disease (amyotrophic lateral sclerosis (ALS), familial ALS (fALS), progressive muscular atrophy (PMA) and primary lateral sclerosis (PLS)) using multiple point stimulation motor unit number estimation (MUNE), transcranial magnetic stimulation (TMS), proton magnetic resonance spectroscopic imaging (1H MRSI), diffusion tensor imaging (MRDTI), and clinical measures at baseline and every 3 months thereafter for 15 months. Substantial differences in MUNE were noted among the motor neuron disease subgroups (P = 0.0005) and mean values for each motor neuron disease subgroup were significantly lower vs. controls (ALS = 76, fALS = 80, PMA = 29, and PLS = 174) vs. the normal control average (267). MUNE correlated well with % FVC (r = 0.32; P = 0.01), manual muscle testing (r = 0.52; P < 0.0005), grip strength (r = 0.34; P = 0.007), and pinch strength (r = 0.49; P < 0.0005). Overall, MUNE showed the greatest significant change over time of any measure, clinical or otherwise, tested in this study (-2.35 linear trend % change per month, mean). MUNE clearly delineates lower motor neuron dysfunction, strongly correlates with important clinical functions (such as strength and respiration) and is a highly sensitive marker of disease progression over time. These features make MUNE an important tool for both the study of the pathophysiology of the motor neuron diseases, as well as an important measure for incorporation into future clinical trials.

Physical activity, diet, and risk of Alzheimer disease.

CONTEXT: Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease (AD) risk but their combined association has not been investigated. OBJECTIVE: To investigate the combined association of diet and physical activity with AD risk. DESIGN, SETTING, AND PATIENTS: Prospective cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York, New York, with both diet and physical activity information available. Standardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006. Adherence to a Mediterranean-type diet (scale of 0-9; trichotomized into low, middle, or high; and dichotomized into low or high) and physical activity (sum of weekly participation in various physical activities, weighted by the type of physical activity [light, moderate, vigorous]; trichotomized into no physical activity, some, or much; and dichotomized into low or high), separately and combined, were the main predictors in Cox models. Models were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, body mass index, smoking status, depression, leisure activities, a comorbidity index, and baseline Clinical Dementia Rating score. MAIN OUTCOME MEASURE: Time to incident AD. RESULTS: A total of 282 incident AD cases occurred during a mean (SD) of 5.4 (3.3) years of follow-up. When considered simultaneously, both Mediterranean-type diet adherence (compared with low diet score, hazard ratio [HR] for middle diet score was 0.98 [95% confidence interval {CI}, 0.72-1.33]; the HR for high diet score was 0.60 [95% CI, 0.42-0.87]; P = .008 for trend) and physical activity (compared with no physical activity, the HR for some physical activity was 0.75 [95% CI, 0.54-1.04]; the HR for much physical activity was 0.67 [95% CI, 0.47-0.95]; P = .03 for trend) were associated with lower AD risk. Compared with individuals neither adhering to the diet nor participating in physical activity (low diet score and no physical activity; absolute AD risk of 19%), those both adhering to the diet and participating in physical activity (high diet score and high physical activity) had a lower risk of AD (absolute risk, 12%; HR, 0.65 [95% CI, 0.44-0.96]; P = .03 for trend). CONCLUSION: In this study, both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD.

The Historical Progression From ADL Scrutiny to IADL to Advanced ADL: Assessing Functional Status in the Earliest Stages of Dementia.

Background: Decrements in instrumental activities (IADL) have been observed in the prodromal phase of dementia. Given the long predementia stage in neurodegenerative diseases, it has been proposed that subtle functional changes may precede clinical IADL impairment. Incorporating more challenging advanced ADLs (eg, volunteer work) into the assessment process may increase the sensitivity of functional measures, thus expanding the window for monitoring or interventions. Methods: Longitudinal cohort study was used (follow-ups, 18-24 month), with subjects aged 60 and older (n = 3,635). To elucidate the relationship between cognitive ability and functional status we employed an IADL scale with an extended range (ADL-extended; includes IADL but also more challenging advanced ADLs) that meets item response theory properties of dimensionality, monotonicity, and item hierarchy. Procedures involved (a) a dynamic change model employed to inspect the temporal relationship between ADL-extended and cognitive status and (b) Cox proportional hazards to assess the risk of incident dementia based on ADL-extended scores. Results: Growth curve modeling: baseline ADL-extended was significantly associated with all four cognitive domains investigated. Worse baseline ADL-extended was associated with more rapid declines in speed/executive function, and worse baseline memory was associated with more rapid declines in ADL-extended; a concurrent association was found for language and ADL-extended. Cox model: the risk of dementia was decreased for each additional ADL-extended item endorsed (hazard ratio [HR], 0.85; 95% confidence interval = 0.81-0.90). Conclusions: An increased risk of dementia could be observed in the ADL-extended items, which reflects an area of the functional continuum beyond IADL competencies.

Mild parkinsonian signs and plasma homocysteine concentration in community-dwelling elderly individuals.

OBJECTIVE: To determine whether plasma homocysteine (Hcy) concentration is associated with mild parkinsonian signs (MPS) in community-dwelling elderly individuals. DESIGN: Cross-sectional analyses of a population-based cohort study. SETTING: Washington Heights-Inwood, New York. Patients Persons without dementia 65 years and older. Main Outcome Measure Participants underwent an abbreviated motor portion of the Unified Parkinson's Disease Rating Scale. Each participant was assigned an MPS score (range, 0-40). The Hcy concentration was measured from plasma. All analyses were cross-sectional. RESULTS: There were 369 participants (mean +/- SD age, 77.8 +/- 6.0 years; mean +/- SD MPS score, 1.51 +/- 2.55; mean +/- SD plasma Hcy concentration, 17.3 +/- 6.5 mumol/L). Mean +/- SD MPS scores in plasma Hcy concentration quintiles were as follows: lowest quintile, 1.15 +/- 1.77; second quintile, 1.18 +/- 1.88; third quintile, 1.64 +/- 2.93; fourth quintile, 1.45 +/- 2.17; and highest quintile, 2.12 +/- 3.49 (84.3% higher than 1.15) (P = .02). In an unadjusted linear regression model, plasma Hcy concentration was associated with log MPS score (dependent variable) (P = .008). In a linear regression model that adjusted for confounding variables, plasma Hcy concentration was associated with log MPS score (P = .04). CONCLUSIONS: These data indicate that MPS are associated with higher plasma Hcy concentrations. Prospective neuroimaging as well as clinical-pathological studies would further our understanding of several mechanisms that could underlie the observed association.

The heritability of abstract reasoning in Caribbean Latinos with familial Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) is under substantial genetic influence. To better understand the genetic influence on component phenotypes of AD, we estimated the heritability (h(2)) of abstract reasoning and examined its relation with apolipoprotein epsilon 4 (APOE-epsilon 4). METHODS: We studied abstract reasoning in 1,116 individuals from 210 Caribbean Hispanic families with late onset AD, using the similarities subtest scores from the Wechsler Adult Intelligence Scale. We computed h(2), then performed analysis of variance to examine the effect of APOE-epsilon 4. RESULTS: Abstract reasoning was highly heritable (h(2)(unadjusted) = 79.9%). After adjusting for covariates, the h(2) was reduced to 32.6%, with education accounting for 40.8% of the variance. The APOE-epsilon 4 allele had no effect. CONCLUSION: Abstract reasoning was strongly influenced by genetic factors and education. Genes other than APOE contribute to the inheritance of abstract reasoning ability.

Functional correlates and prevalence of mild parkinsonian signs in a community population of older people.

BACKGROUND: Mild parkinsonian signs (MPS) are associated with incident dementia and an increased risk of mortality. To our knowledge, the functional correlates of MPS have not been studied. OBJECTIVES: To study the functional correlates of MPS, including self-reported and performance-based measures of function, and to determine the prevalence of MPS in a cohort of community-dwelling older people (aged >or=65 years). DESIGN: Participants (N = 1866) in the Washington Heights-Inwood Columbia Aging Project underwent a neurological assessment that included a modified motor portion of the Unified Parkinson's Disease Rating Scale, which yielded a parkinsonian sign score (range, 0-40) and parkinsonian sign subscores (axial function, rigidity, and tremor). A functional assessment included 3 self-reported measures of function and 2 performance-based tests. Participants with Parkinson disease were excluded. RESULTS: Mild parkinsonian signs were present in 469 (25.1%) of the 1866 participants. The parkinsonian sign score was correlated with functional and performance-based test scores (r = 0.24-0.32, P<.001). The axial function and rigidity subscores correlated to a greater extent with functional and performance-based test scores than did the tremor subscore. In analysis of covariance models, excluding participants with dementia and adjusting for age, sex, ethnicity, education, depressive symptoms, and medical illnesses (eg, arthritis), the parkinsonian sign score and age were strongly and independently associated with functional scores. CONCLUSIONS: Mild parkinsonian signs, and particularly axial dysfunction, were associated with functional disability, including self-reported and performance-based measures of functional difficulty. Given the high prevalence of these signs in elderly persons, MPS may be a significant indicator of disability in elderly persons.

Implementing diagnostic criteria and estimating frequency of mild cognitive impairment in an urban community.

BACKGROUND: Reported rates of mild cognitive impairment (MCI) range widely depending on methodologic differences, including specific sample characteristics, cognitive measures used, normative samples used for neuropsychological tests, and diagnostic criteria. OBJECTIVES: To operationalize diagnostic criteria for MCI and examine the frequency of MCI in ethnically and linguistically diverse elders (individuals older than 65 years). DESIGN: Prospective, community-based longitudinal cohort study. SETTING: Northern Manhattan, New York, NY. PARTICIPANTS: A cohort of 1315 nondemented elderly participants. MAIN OUTCOME MEASURE: A diagnosis of MCI was assigned retrospectively on the basis of comprehensive neuropsychological, functional, and neurologic assessments. Amnestic MCI, as well as forms of mild impairment with other cognitive characteristics, were classified. RESULTS: The frequency of amnestic MCI was 5.0% (95% confidence interval, 3.8-6.2). Other subtypes of MCI ranged in frequency from 2.1% to 6.2%. Mild cognitive impairment was more common among those older than 75 years compared with those aged 65 to 75 years. Individuals with fewer than 9 years of schooling were more likely to meet MCI criteria. Apolipoprotein (APOE) E4 allele was more frequent among those with amnestic MCI. CONCLUSIONS: When proper normative values are used, only age and education, and not race or ethnicity, are associated with higher frequency of MCI. The proportion of nondemented elders with isolated memory deficits is smaller than the proportion with deficits in multiple cognitive domains. The strong association of the APOE E4 allele with only amnestic MCI suggests that there are likely to be multiple causes of cognitive impairment and differential rates of conversion to Alzheimer disease within the cognitive subtypes of MCI.

Cognitive decline and literacy among ethnically diverse elders.

Researchers on genetic and environmental influences on risk for Alzheimer's disease must be prepared for the growing ethnic and racial diversity of our participants. Within the investigation, years of education has typically served as a proxy for cognitive reserve, which may be one factor in influencing risk of cognitive decline among aging people. However, among ethnic minorities, years of education is a poor reflection of the value of educational experience and native ability. This study was conducted among 1002 ethnically diverse English-speaking residents of Northern Manhattan who were cognitively and functionally normal at a baseline evaluation. We found that literacy level was a better predictor of decline in memory, executive function, and language skills than was years of education. The results of this study suggest that in an ethnically diverse cohort, literacy level should be considered as a mediator of the interactions of biological and environmental factors on cognitive decline.

Elevated sex-hormone binding globulin in elderly women with Alzheimer's disease.

BACKGROUND: Hormone levels change significantly with increasing age. These changes may be related to, or be associated with, the emergence of age-related diseases, such as Alzheimer's disease (AD). METHODS: Five hundred and seventy-six women over the age of 65 were studied from the Washington Heights-Inwood Columbia Aging Project (WHICAP). These women were selected from a group of healthy Medicare beneficiaries that were aged 65 and older living in the geographically defined area of northern Manhattan in New York City. Serum levels of estrone (E1), estradiol (E2), total testosterone (TT), dehydroepiandosterone (DHEA), luteinizing hormone (LH), follicle stimulating hormone (FSH), and sex-hormone binding globulin (SHBG) were measured. RESULTS: Significant differences were found between patients with AD and controls only in the level of SHBG, which was 20% higher in patients compared to controls (68.5nmol/l versus 54.7nmol/l, P<0.001). We also estimated levels of total E2 because after menopause, E2 is largely derived from E1. AD patients had significantly lower levels of estimated E2 (AD 0.46 versus controls 0.49, P<0.01). Differences remained significant after adjusting for age, ethnic group, education, and body mass index (BMI). CONCLUSIONS: A marked increase in SHBG levels was found in AD patients. SHBG normally responds to circulating testosterone and estrogen, therefore, elevated SHBG suggests an abnormal increase in its production and regulation. Further work is needed to clarify the cause and consequences of this observation.

Parkinsonian signs in older people in a community-based study: risk of incident dementia.

BACKGROUND: Mild parkinsonian signs occur in 30% to 40% of community-dwelling older people. In a cross-sectional study, the severity of these signs was greater in people with dementia than in people without dementia. OBJECTIVE: To determine whether baseline mild parkinsonian signs are a predictor of incident dementia. DESIGN: A prospective, longitudinal study of community-dwelling older people who did not have dementia or Parkinson disease at baseline. METHODS: A neurological examination was performed on 1028 residents aged 65 years or older in the Washington Height-Inwood community in northern Manhattan, NY. Parkinsonian signs were rated with an abbreviated Unified Parkinson's Disease Rating Scale, resulting in a parkinsonian sign score (range, 0-40). The risk of incident dementia was assessed using Cox proportional hazards models. In some analyses, data from the modified Unified Parkinson's Disease Rating Scale were divided into 3 domains: rigidity, axial function, and tremor at rest. RESULTS: The mean duration of follow-up was 5.6 years, and 224 participants (21.8%) developed dementia. In a Cox model, the risk of incident dementia was 57% higher in participants with a baseline parkinsonian sign score of 2 vs 0 (relative risk, 1.56; 95% confidence interval, 1.04-2.33; P =.03). In a second Cox model, the baseline parkinsonian sign score was associated with incident dementia (relative risk, 1.08; 95% confidence interval, 1.01-1.16; P =.02) independent of associations with baseline age, education, ethnicity, diabetes mellitus, and stroke. CONCLUSIONS: Baseline mild parkinsonian signs are a predictor of incident dementia. Although these signs are mild, they are not prognostically benign. Brain imaging and postmortem examinations might further our insight into the anatomical and pathological basis for mild parkinsonian signs.

Late-life depression, mild cognitive impairment, and dementia.

OBJECTIVE: To evaluate the association of late-life depression with mild cognitive impairment (MCI) and dementia in a multiethnic community cohort. DESIGN AND SETTING: A cohort study was conducted in Northern Manhattan, New York, New York. PARTICIPANTS: A total of 2160 community-dwelling Medicare recipients aged 65 years or older were included in the study. METHODS: Depression was assessed using the 10-item version of the Center for Epidemiological Studies Depression scale (CES-D) and defined by a CES-D score of 4 or more. We used logistic regression for cross-sectional association analyses and proportional hazards regression for longitudinal analyses. MAIN OUTCOME MEASURES: Mild cognitive impairment dementia, and progression from MCI to dementia were the main outcome measures. We also used subcategories of MCI (amnestic and nonamnestic), and dementia (probable Alzheimer disease and vascular dementia, including possible Alzheimer disease with stroke). RESULTS: Baseline depression was associated with prevalent MCI (odds ratio, 1.4; 95% CI, 1.1-1.9) and dementia (2.2; 1.6-3.1). Baseline depression was associated with an increased risk of incident dementia (hazard ratio [HR], 1.7; 95% CI, 1.2-2.3) but not with incident MCI (0.9; 0.7-1.2). Persons with MCI and coexisting depression at baseline had a higher risk of progression to dementia (HR, 2.0; 95% CI, 1.2-3.4), especially vascular dementia (4.3; 1.1-17.0), but not Alzheimer disease (1.9; 1.0-3.6). CONCLUSION: The association of depression with prevalent MCI and with progression from MCI to dementia, but not with incident MCI, suggests that depression accompanies cognitive impairment but does not precede it.

Telephone-based identification of mild cognitive impairment and dementia in a multicultural cohort.

BACKGROUND: Telephone-based interviews can be used for screening and to obtain key study outcomes when participants in longitudinal studies die or cannot be seen in person, but must be validated among ethnically and educationally diverse people. OBJECTIVE: To determine the accuracy of a telephone interview in classifying (1) demented from nondemented participants, (2) cognitively impaired participants from cognitively normal participants, and (3) participants with mild cognitive impairment (MCI) from those with normal cognition or (4) MCI from dementia among an ethnically and educationally diverse community-based sample. METHOD: The sample consisted of 377 (30.5% non-Hispanic white, 34.7% non-Hispanic black, and 33.7% Caribbean Hispanic) older adults. The validation standard was diagnosis of dementia and MCI based on in-person evaluation. The Telephone Interview for Cognitive Status (TICS) and the Dementia Questionnaire (DQ) were administered within the same assessment wave. RESULTS: The sample included 256 people (67.9%) with normal cognition, 68 (18.0%) with MCI, and 53 (14.1%) with dementia. Validity of the TICS was comparable among non-Hispanic whites, non-Hispanic blacks, and Hispanics. Among non-Hispanic whites, the DQ had better discrimination of those with dementia from those without dementia and from those with MCI than among other racial/ethnic groups. Telephone measures discriminated best when used to differentiate demented from nondemented participants (88% sensitivity and 87% specificity for the TICS; 66% sensitivity and 89% specificity for DQ) and when used to differentiate cognitively normal participants from those with cognitive impairment (ie, MCI and dementia combined; 73% sensitivity and 77% specificity for the TICS; 49% sensitivity and 82% specificity for DQ). When demographics and prior memory test performance were used to calculate pretest probability, consideration of the telephone measures significantly improved diagnostic validity. CONCLUSIONS: The TICS has high diagnostic validity for identification of dementia among ethnically diverse older adults, especially when supported by the DQ and prior visit data. However, telephone interview data were unable to reliably distinguish MCI from normal cognition.