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1.
J Prev Alzheimers Dis ; 11(3): 639-648, 2024.
Article in English | MEDLINE | ID: mdl-38706280

ABSTRACT

BACKGROUND: Many Alzheimer's Disease (AD) clinical trials have failed to demonstrate treatment efficacy on cognition. It is conceivable that a complex disease like AD may not have the same treatment effect due to many heterogeneities of disease processes and individual traits. OBJECTIVES: We employed an individual-level treatment response (ITR) approach to determine the characteristics of treatment responders and estimated time saved in cognitive decline using the Internet-based Conversational Engagement Clinical Trial (I-CONECT) behavioral intervention study as a model. DESIGN AND SETTING: I-CONECT is a multi-site, single-blind, randomized controlled trial aimed to improve cognitive functions through frequent conversational interactions via internet/webcam. The experimental group engaged in video chats with study staff 4 times/week for 6 months; the control group received weekly 10-minute check-in phone calls. PARTICIPANTS: Out of 186 randomized participants, current study used 139 participants with complete information on both baseline and 6-month follow-up (73 with mild cognitive impairment (MCI), 66 with normal cognition; 64 in the experimental group, and 75 in the control group). MEASUREMENTS: ITR scores were generated for the Montreal Cognitive Assessment (MoCA) (global cognition, primary outcome) and Category Fluency Animals (CFA) (semantic fluency, secondary outcome) that showed significant efficacy in the trial. ITR scores were generated through 300 iterations of 3-fold cross-validated random forest models. The average treatment difference (ATD) curve and the area between the curves (ABC) were estimated to measure the heterogeneity of treatment responses. Responder traits were identified using SHapley Additive exPlanations (SHAP) and decision tree models. The time saved in cognitive decline was explored to gauge clinical meaningfulness. RESULTS: ABC statistics showed substantial heterogeneity in treatment response with MoCA but modest heterogeneity in treatment response with CFA. Age, cognitive status, time spent with family and friends, education, and personality were important characteristics that influenced treatment responses. Intervention group participants in the upper 30% of ITR scores demonstrated potential delays of 3 months in semantic fluency (CFA) and 6 months in global cognition (MoCA), assuming a 5-fold faster natural cognitive decline compared to the control group during the post-treatment period. CONCLUSIONS: ITR-based analyses are valuable in profiling treatment responders for features that can inform future trial design and clinical practice. Reliably measuring time saved in cognitive decline is an area of ongoing research to gain insight into the clinical meaningfulness of treatment.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Precision Medicine , Humans , Male , Female , Cognitive Dysfunction/therapy , Precision Medicine/methods , Alzheimer Disease/therapy , Alzheimer Disease/psychology , Aged , Single-Blind Method , Internet , Behavior Therapy/methods , Aged, 80 and over
2.
J Prev Alzheimers Dis ; 10(2): 301-313, 2023.
Article in English | MEDLINE | ID: mdl-36946457

ABSTRACT

Clinical trials are increasingly focused on pre-manifest and early Alzheimer's disease (AD). Accurately predicting clinical progressions from normal to MCI or from MCI to dementia/AD versus non-progression is challenging. Accurate identification of symptomatic progressors is important to avoid unnecessary treatment and improve trial efficiency. Due to large inter-individual variability, biomarker positivity and comorbidity information are often insufficient to identify those destined to have symptomatic progressions. Using only clinical variables, we aimed to predict clinical progressions, estimating probabilities of progressions with a small set of variables selected by machine learning approaches. This work updates our previous work that was applied to the National Alzheimer's Coordinating Center (NACC) Uniform Data Set Version 2 (V2), by using the most recent version (V3) with additional analyses. We generated a user-friendly conversion probability calculator which can be used for effectively pre-screening trial participants.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/diagnosis , Cognitive Dysfunction/diagnosis , Disease Progression , Sensitivity and Specificity , Machine Learning
3.
J Prev Alzheimers Dis ; 3(2): 85-91, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27709107

ABSTRACT

BACKGROUND: Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. OBJECTIVE: To correlate measures of cerebral vascular pathology with cognitive trajectories. SETTING: Observational study. PARTICIPANTS: A cohort of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82 percent of whom had at least two cognitive assessments within the last six years of life was compiled from six centers conducting longitudinal studies. MEASUREMENTS: For each cognitive domain: immediate and delayed memory, language, and naming, three trajectories were examined: good, intermediate, and poor cognition. The probability of a participant belonging to each trajectory was associated with measures of cerebral vascular pathology after adjustment for demographics, APOE, and Alzheimer neuropathology. RESULTS: A large proportion of the cohort (72-94%) experienced good or intermediate cognition in the four domains examined. The presence of arteriolosclerosis and the presence of lacunar infarcts doubled the odds of belonging to the poor cognitive trajectory for language when compared to the good trajectory. The presence of lacunar infarcts increased the odds of an intermediate or poor trajectory for immediate and delayed recall while the presence of large artery infarcts increased the odds of poor trajectories for all four cognitive domains examined. Microinfarcts and cerebral amyloid angiopathy had little effect on the trajectories. CONCLUSION: Indicators of cerebral vascular pathology act differently on late life cognition.

4.
Neuroimage Clin ; 8: 224-9, 2015.
Article in English | MEDLINE | ID: mdl-26106546

ABSTRACT

OBJECTIVE: White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify 'WM at risk', or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up. METHODS: Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI. RESULTS: CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time. CONCLUSIONS: A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences.


Subject(s)
Aging/pathology , Cerebrovascular Circulation/physiology , Magnetic Resonance Imaging/methods , White Matter/pathology , Aged , Aged, 80 and over , Aging/physiology , Female , Humans , Male , Spin Labels , White Matter/blood supply
5.
Obs Stud ; 1(2015): 56-73, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25984574

ABSTRACT

Longitudinal cognitive trajectories and other factors associated with mixed neuropathologies (such as Alzheimer's disease with co-occurring cerebrovascular disease) remain incompletely understood, despite being the rule and not the exception in older populations. The Statistical Modeling of Aging and Risk of Transition study (SMART) is a consortium of 11 different high-quality longitudinal studies of aging and cognition (N=11,541 participants) established for the purpose of characterizing risk and protective factors associated with subtypes of age-associated mixed neuropathologies (N=3,001 autopsies). While brain donation was not required for participation in all SMART cohorts, most achieved substantial autopsy rates (i.e., > 50%). Moreover, the studies comprising SMART have large numbers of participants who were followed from intact cognition and transitioned to cognitive impairment and dementia, as well as participants who remained cognitively intact until death. These data provide an exciting opportunity to apply sophisticated statistical methods, like Markov processes, that require large, well-characterized samples. Thus, SMART will serve as an important resource for the field of mixed dementia epidemiology and neuropathology.

6.
Neurology ; 78(24): 1946-52, 2012 Jun 12.
Article in English | MEDLINE | ID: mdl-22689734

ABSTRACT

OBJECTIVE: To determine whether unobtrusive long-term in-home assessment of walking speed and its variability can distinguish those with mild cognitive impairment (MCI) from those with intact cognition. METHODS: Walking speed was assessed using passive infrared sensors fixed in series on the ceiling of the homes of elderly individuals participating in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study. Latent trajectory models were used to analyze weekly mean speed and walking speed variability (coefficient of variation [COV]). RESULTS: ISAAC participants living alone included 54 participants with intact cognition, 31 participants with nonamnestic MCI (naMCI), and 8 participants with amnestic MCI at baseline, with a mean follow-up of 2.6 ± 1.0 years. Trajectory models identified 3 distinct trajectories (fast, moderate, and slow) of mean weekly walking speed. Participants with naMCI were more likely to be in the slow speed group than in the fast (p = 0.01) or moderate (p = 0.04) speed groups. For COV, 4 distinct trajectories were identified: group 1, the highest baseline and increasing COV followed by a sharply declining COV; groups 2 and 3, relatively stable COV; and group 4, the lowest baseline and decreasing COV. Participants with naMCI were more likely to be members of either highest or lowest baseline COV groups (groups 1 or 4), possibly representing the trajectory of walking speed variability for early- and late-stage MCI, respectively. CONCLUSION: Walking speed and its daily variability may be an early marker of the development of MCI. These and other real-time measures of function may offer novel ways of detecting transition phases leading to dementia.


Subject(s)
Cognitive Dysfunction/physiopathology , Dementia/diagnosis , Disease Progression , Gait/physiology , Walking/physiology , Activities of Daily Living , Aged , Aged, 80 and over , Dementia/physiopathology , Female , Follow-Up Studies , Humans , Male , Risk Factors
7.
Neurology ; 78(4): 241-9, 2012 Jan 24.
Article in English | MEDLINE | ID: mdl-22205763

ABSTRACT

OBJECTIVE: To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders. METHODS: Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n = 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes. RESULTS: Mean age was 87 ± 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine ω-3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine ω-3 pattern and white matter hyperintensity volume. CONCLUSION: Distinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population.


Subject(s)
Aging/physiology , Aging/psychology , Biomarkers , Brain/growth & development , Brain/physiology , Cognition/physiology , Nutritional Status , Aged, 80 and over , Apolipoprotein E3/genetics , Cohort Studies , Demography , Diet , Fatty Acids, Omega-3/blood , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Polymerase Chain Reaction , Psychometrics , Regression Analysis , Risk Factors , Vitamins/blood
8.
Neurology ; 72(4): 354-60, 2009 Jan 27.
Article in English | MEDLINE | ID: mdl-19171833

ABSTRACT

BACKGROUND: Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms. METHODS: A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups. RESULTS: In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease. CONCLUSION: Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.


Subject(s)
Alzheimer Disease/etiology , Alzheimer Disease/pathology , Aged , Aged, 80 and over , Alzheimer Disease/psychology , Brain/pathology , Case-Control Studies , Cognition/physiology , Cohort Studies , Dementia/etiology , Dementia/pathology , Dementia/psychology , Female , Hippocampus/pathology , Humans , Longitudinal Studies , Male , Oregon , Organ Size/physiology , Plaque, Amyloid/pathology , Risk Factors
9.
Neurology ; 70(24): 2291-8, 2008 Jun 10.
Article in English | MEDLINE | ID: mdl-18509093

ABSTRACT

INTRODUCTION: Observational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk. METHODS: We pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs. RESULTS: Of 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13). CONCLUSIONS: In this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans.


Subject(s)
Alzheimer Disease/prevention & control , Amyloid beta-Peptides/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Neuroprotective Agents/therapeutic use , Peptide Fragments/metabolism , Acetaminophen/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Analgesics, Non-Narcotic/therapeutic use , Aspirin/therapeutic use , Cohort Studies , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk Factors
10.
Neurology ; 70(19 Pt 2): 1809-17, 2008 May 06.
Article in English | MEDLINE | ID: mdl-18305231

ABSTRACT

OBJECTIVE: To assess the feasibility, safety, and efficacy of Ginkgo biloba extract (GBE) on delaying the progression to cognitive impairment in normal elderly aged 85 and older. METHODS: Randomized, placebo-controlled, double-blind, 42-month pilot study with 118 cognitively intact subjects randomized to standardized GBE or placebo. Kaplan-Meier estimation, Cox proportional hazard, and random-effects models were used to compare the risk of progression from Clinical Dementia Rating (CDR) = 0 to CDR = 0.5 and decline in episodic memory function between GBE and placebo groups. RESULTS: In the intention-to-treat analysis, there was no reduced risk of progression to CDR = 0.5 (log-rank test, p = 0.06) among the GBE group. There was no less of a decline in memory function among the GBE group (p = 0.05). In the secondary analysis, where we controlled the medication adherence level, the GBE group had a lower risk of progression from CDR = 0 to CDR = 0.5 (HR = 0.33, p = 0.02), and a smaller decline in memory scores (p = 0.04). There were more ischemic strokes and TIAs in the GBE group (p = 0.01). CONCLUSIONS: In unadjusted analyses, Ginkgo biloba extract (GBE) neither altered the risk of progression from normal to Clinical Dementia Rating (CDR) = 0.5, nor protected against a decline in memory function. Secondary analysis taking into account medication adherence showed a protective effect of GBE on the progression to CDR = 0.5 and memory decline. Results of larger prevention trials taking into account medication adherence may clarify the effectiveness of GBE. More stroke and TIA cases observed among the GBE group requires further study to confirm.


Subject(s)
Cognition Disorders/prevention & control , Dementia/prevention & control , Drugs, Chinese Herbal/administration & dosage , Ginkgolides/administration & dosage , Aged, 80 and over , Brain/drug effects , Brain/physiopathology , Cerebral Hemorrhage/chemically induced , Cognition Disorders/physiopathology , Cohort Studies , Dementia/physiopathology , Disease Progression , Double-Blind Method , Drugs, Chinese Herbal/adverse effects , Female , Ginkgolides/adverse effects , Humans , Male , Memory Disorders/drug therapy , Memory Disorders/physiopathology , Memory Disorders/prevention & control , Models, Statistical , Neuroprotective Agents/administration & dosage , Neuropsychological Tests , Nootropic Agents/administration & dosage , Nootropic Agents/adverse effects , Pilot Projects , Placebos , Risk Reduction Behavior , Treatment Outcome
11.
Neurology ; 65(8): 1210-7, 2005 Oct 25.
Article in English | MEDLINE | ID: mdl-16247047

ABSTRACT

OBJECTIVE: To examine the association between alcohol use and cognitive decline in a longitudinal study of a representative elderly community sample free of dementia at baseline. METHODS: Cognitive functions and self-reported drinking habits were assessed at 2-year intervals over an average of 7 years of follow-up. Cognitive measures, grouped into composites, were examined in association with alcohol consumption. Trajectory analyses identified latent homogeneous groups with respect to alcohol use frequency over time, and their association with average decline over the same period in each cognitive domain. Models controlled for age, sex, education, depression, smoking, general mental status (Mini-Mental State Examination [MMSE]), performance on the given test at baseline, and subsequent new-onset dementia during follow-up. RESULTS: The authors found three homogeneous trajectories that they characterized as no drinking, minimal drinking, and moderate drinking. Few heavy drinkers were identified in this elderly cohort. Compared to no drinking, both minimal and moderate drinking were associated with lesser decline on the MMSE and Trailmaking tests. Minimal drinking was also associated with lesser decline on tests of learning and naming. These associations were more pronounced when comparing current drinkers to former drinkers (quitters) than to lifelong abstainers. CONCLUSION: In a representative elderly cohort over an average of 7 years, a pattern of mild-to-moderate drinking, compared to not drinking, was associated with lesser average decline in cognitive domains over the same period.


Subject(s)
Aging/physiology , Alcohol Drinking/adverse effects , Alcohol-Induced Disorders, Nervous System/epidemiology , Cognition Disorders/chemically induced , Cognition Disorders/epidemiology , Age Factors , Aged , Aged, 80 and over , Alcohol Amnestic Disorder/epidemiology , Alcohol Amnestic Disorder/psychology , Alcohol-Induced Disorders, Nervous System/psychology , Causality , Cognition Disorders/psychology , Cohort Studies , Disease Progression , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Memory Disorders/chemically induced , Memory Disorders/epidemiology , Memory Disorders/psychology , Neuropsychological Tests , Pennsylvania/epidemiology
12.
Health Mark Q ; 19(3): 3-20, 2002.
Article in English | MEDLINE | ID: mdl-12077808

ABSTRACT

Both intensified competition and greater consumer participation in the choice process for healthcare has increased the importance of advertising for health care providers and seriously challenged many of the preconceptions regarding advertising. This study investigates the effectiveness of advertising under conditions of high and low involvement using the Elaboration Likelihood Model to develop hypotheses that are tested in a 2 x 2 x 2 experimental design. The study findings provide insights into the influence of message content and message source on consumers categorized as high or low involvement. It was found that consumers classified as high-involvement are more influenced by a core service-relevant message than those consumers classified as low-involvement. Moreover, a non-physician spokesperson was found to have as much or more influence as a physician spokesperson regardless of the consumers' involvement level.


Subject(s)
Community Participation/statistics & numerical data , Hospital Administration , Marketing of Health Services/organization & administration , Advertising , Choice Behavior , Female , Humans , Likelihood Functions , Male , Northwestern United States , Patient Participation/statistics & numerical data , Persuasive Communication , Physician-Patient Relations
13.
Neurology ; 57(6): 985-9, 2001 Sep 25.
Article in English | MEDLINE | ID: mdl-11571321

ABSTRACT

OBJECTIVE: To determine overall and age-specific incidence rates of AD in a rural, population-based cohort in Ballabgarh, India, and to compare them with those of a reference US population in the Monongahela Valley of Pennsylvania. METHODS: A 2-year, prospective, epidemiologic study of subjects aged > or =55 years utilizing repeated cognitive and functional ability screening, followed by standardized clinical evaluation using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for the diagnosis, and the Clinical Dementia Rating scale for the staging, of dementia and AD. RESULTS: Incidence rates per 1000 person-years for AD with CDR > or =0.5 were 3.24 (95% CI: 1.48-6.14) for those aged > or =65 years and 1.74 (95% CI: 0.84-3.20) for those aged > or =55 years. Standardized against the age distribution of the 1990 US Census, the overall incidence rate in those aged > or =65 years was 4.7 per 1000 person-years, substantially lower than the corresponding rate of 17.5 per 1000 person-years in the Monongahela Valley. CONCLUSION: These are the first AD incidence rates to be reported from the Indian subcontinent, and they appear to be among the lowest ever reported. However, the relatively short duration of follow-up, cultural factors, and other potential confounders suggest caution in interpreting this finding.


Subject(s)
Alzheimer Disease/epidemiology , Cross-Cultural Comparison , Developing Countries , Rural Population/statistics & numerical data , Age Factors , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Incidence , India/epidemiology , Male , Middle Aged , United States/epidemiology
14.
Hum Biol ; 73(1): 135-44, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11332642

ABSTRACT

Allele frequencies are most often reported from small convenience samples of unknown demographics and limited generalizability. We determined the distribution of apolipoprotein E genotype (APOE) and allele frequencies for a large, well-defined, representative, rural, population-based sample (n = 4450) aged 55-95 years in Ballabgarh, in the northern Indian state of Haryana. The overall APOE E*2, E*3, and E*4 allele frequencies were 0.039, 0.887, and 0.073, respectively; frequencies are also reported by age, sex, and religious/caste groups. The APOE*4 frequency is among the lowest reported anywhere in the world. APOE allele frequencies did not vary significantly by age or sex in this study. To our knowledge, this is the largest Indian sample ever genotyped for the APOE polymorphism. The representativeness of the sample and its known demographics provide a much-needed normative background for studies of gene-disease associations.


Subject(s)
Apolipoproteins E/genetics , Polymorphism, Genetic , Age Distribution , Aged , Aged, 80 and over , Female , Gene Frequency , Humans , India , Male , Middle Aged , Rural Population , Sex Distribution , Social Class
15.
Thyroid ; 11(12): 1177-85, 2001 Dec.
Article in English | MEDLINE | ID: mdl-12186506

ABSTRACT

The effect(s) of hypothyroidism on adult brain cognitive function are poorly understood. We performed a series of neuropsychological tests in 13 thyroid cancer patients while they continued to take their usual dose of levothyroxine (LT4) and again after discontinuing thyroid hormone. Three euthyroid subjects were also tested twice to assess the effect of repeated testing on performance. The tests assessed memory, mood, and attentional resources and controlled for the practice effects of repeated testing. The mean thyrotropin (TSH) on LT4 was 0.56 +/- 0.76 mU/L and while hypothyroid was 69 +/- 33 mU/L. While hypothyroid, the mean Beck depression score was significantly higher (15.31 +/- 9.41 hypothyroid vs. 7.31 +/- 4.82 on LT4) and the subjects rated themselves worse relative to functional memory, concentration, thinking, alertness, and motivation. Hypothyroidism was associated with a decrease in retrieval from memory (p = 0.0034), and this effect could not be attributed to depression or to practice effects. Thyroid state did not affect immediate recall, verbal learning, inhibitory efficiency, information processing speed, or attention switching. Athyrosis is associated with a decrement in delayed recall of verbal information but not in other objective measures of cognition, suggesting that the memory decrement of hypothyroidism is not caused by a generalized reduction in attentional resources.


Subject(s)
Cognition , Hypothyroidism/complications , Hypothyroidism/physiopathology , Memory Disorders/etiology , Adult , Depression , Educational Status , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Self Concept , Thyroid Neoplasms/therapy , Thyrotropin/blood , Thyroxine/blood , Thyroxine/therapeutic use
16.
Appl Neuropsychol ; 8(4): 193-203, 2001.
Article in English | MEDLINE | ID: mdl-11989722

ABSTRACT

This study presents normative data for the Speed and Capacity of Language Processing (SCOLP) testfrom an older American sample. The SCOLP comprises 2 subtests: Spot-the-Word, a lexical decision task, providing an estimate of premorbid intelligence, and Speed of Comprehension, providing a measure of information processing speed. Slowed performance may resultfrom normal aging, brain damage (e.g., head injury), or dementing disorders or may represent the intact performance of someone who always performed at the low end of normal. The SCOLP enables the clinician to differentiate between these possibilities. Adequate age-appropriate norms to differentiate dementia from normal aging do not exist. We present data from 424 older community-dwelling Americans (75-94 years old). The results confirm that information processing speed slows with increasing age. By contrast, increasing age has little effect on lexical decision. Thus, our data suggest that the SCOLP shows promise as a tool to help distinguish between normal aging and the early stages of dementia.


Subject(s)
Language , Neuropsychological Tests/standards , Age Factors , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Dementia/diagnosis , Dementia/psychology , Education , Female , Humans , Male , Reading , Reference Values , Sex Factors , United States , Vocabulary
17.
Arch Neurol ; 57(6): 824-30, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10867779

ABSTRACT

BACKGROUND: The APOE*E4 allele of the gene for apolipoprotein E (APOE) has been reported as a risk factor for Alzheimer disease (AD) to varying degrees in different ethnic groups. OBJECTIVE: To compare APOE*E4-AD epidemiological associations in India and the United States in a cross-national epidemiological study. DESIGN: Case-control design within 2 cohort studies, using standardized cognitive screening and clinical evaluation to identify AD and other dementias and polymerase chain reaction to identify APOE genotyping. PARTICIPANTS: Rural community samples, aged 55 years or older (n=4450) in Ballabgarh, India, and 70 years or older (n=886) in the Monongahela Valley region of southwestern Pennsylvania. MAIN OUTCOME MEASURES: Criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable and possible AD and Clinical Dementia Rating (CDR) scale for dementia staging. RESULTS: Frequency of APOE*E4 was significantly lower (P<.001) in Ballabgarh vs the Monongahela Valley (0.07 vs 0.11). Frequency of probable or possible AD, with CDR of at least 1.0, in the Indian vs US samples, was as follows: aged 55 to 69 years, 0.1% (Indian sample only); aged 70 to 79 years, 0.7% vs 3.1%; aged 80 years or older, 4.0% vs 15.7%. Among those aged 70 years or older, adjusted odds ratios (95% confidence interval) for AD among carriers of APOE*E4 vs noncarriers were 3.4 (1.2-9.3) and 2.3 (1.3-4.0) in the Indian and US samples, respectively, and not significantly different between cohorts (P=. 20). CONCLUSION: This first report of APOE*E4 and AD from the Indian subcontinent shows very low prevalence of AD in Ballabgarh, India, but association of APOE*E4 with AD at similar strength in Indian and US samples. Arch Neurol. 2000.


Subject(s)
Alzheimer Disease/genetics , Apolipoproteins E/genetics , Polymorphism, Genetic/genetics , Aged , Aged, 80 and over , Case-Control Studies , Cohort Studies , Cross-Cultural Comparison , Female , Humans , India , Male , Middle Aged , Pennsylvania , Risk Factors , Rural Population , Treatment Outcome , United States
18.
Neurology ; 54(5): 1109-16, 2000 Mar 14.
Article in English | MEDLINE | ID: mdl-10720283

ABSTRACT

OBJECTIVE: To determine incidence rates by age, sex, and education of overall dementia and probable/ possible AD in a largely rural community. METHODS: Ten-year prospective study of a randomly selected community sample aged 65+; biennial cognitive screening followed by standardized clinical evaluation. Incidence rates were estimated for overall dementia (Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised, criteria and Clinical Dementia Rating [CDR]) and for probable/possible AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). RESULTS: The cohort consisted of 1,298 individuals free of dementia at study entry. Among these, 199 incident (new) cases of overall (all-cause) dementia with CDR stage > or = 0.5, including 110 with CDR > or = 1, were detected during follow-up. Among the incident cases, 153 (76.9%) had probable/ possible AD. Age-specific incidence rates are reported for all dementia and for probable/possible AD, by sex and CDR stage. Among all-cause dementias with CDR = 0.5, controlling for age and education, men had a higher incidence rate than women. In the same group, those with less than high school education had significantly higher incidence rates than those with more education. Rates did not vary significantly by sex or education for probable/possible AD or for dementia with CDR > or = 1. CONCLUSIONS: Incidence rates of all dementias and of AD increased with age; men and those with lesser education had higher rates of possible/incipient dementia (CDR = 0.5) in this community. Potential explanations for these sex and education effects are discussed.


Subject(s)
Dementia/epidemiology , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Pennsylvania , Rural Population , Time Factors , United States
19.
Int Psychogeriatr ; 11(3): 235-50, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10547124

ABSTRACT

BACKGROUND: Previous studies of dementia and family caregiving have focused on individuals seeking diagnosis and treatment, and have rarely been conducted in representative community samples. Identifying demented individuals participating in a community survey, we determined (a) the factors associated with demented elderly living alone; (b) the factors associated with the demented elderly having caregivers; (c) the factors associated with increased levels of burden among caregivers of persons with dementia. POPULATION AND METHODS: During an epidemiological survey of a mostly rural U.S. community, the authors identified 116 noninstitutionalized elderly individuals with dementia. These individuals were classified into those living alone and those living with others; both groups were further classified into those with and without identifiable family caregivers. Characteristics of both caregivers and care recipients were examined. RESULTS: Approximately a third of the subjects with dementia lived alone, and only half of them had caregivers. The average age of the caregivers was 67.4 years, and 73% of them were women. Almost half of the caregivers were spouses, whereas almost a third were offspring, of the demented individuals. Over two thirds of caregivers lived with the subjects. Female caregivers were significantly younger than male caregivers. Multivariate analyses revealed that subjects with dementia who were living alone were independently and significantly more likely to be women and to have dementias of shorter duration, lesser severity, and lesser functional impairment than those living with others. Demented subjects with caregivers were more likely to have greater dementia severity, functional impairment, and cognitive impairment and more current cognitive and behavioral symptoms than those without caregivers. Demented subjects whose caregivers reported higher levels of burden were more likely to be women and to have greater dementia severity, functional impairment, and cognitive impairment and more current symptoms than those whose caregivers had no/minimal burden. CONCLUSIONS: These results draw attention to the problems of persons with dementia living alone, particularly those without caregivers. Our data also provide epidemiological confirmation of previous clinical/volunteer studies of dementia caregiving, as well as a preliminary assessment of need in the community at large. Living arrangements and caregiver issues should be taken into account when planning services for the elderly.


Subject(s)
Caregivers , Community Health Services/supply & distribution , Dementia/epidemiology , Aged , Catchment Area, Health , Cost of Illness , Dementia/diagnosis , Female , Health Services for the Aged , Humans , Male , Pennsylvania/epidemiology , Prospective Studies , Severity of Illness Index
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