Structural magnetic resonance imaging (MRI) provides key biomarkers to predict onset and track progression of Alzheimer's disease (AD). However, most published reports of relationships between MRI ...variables and cognition in older adults include racially, ethnically, and socioeconomically homogenous samples. Racial/ethnic differences in MRI variables and cognitive performance, as well as health, socioeconomic status and psychological factors, raise the possibility that brain-behavior relationships may be stronger or weaker in different groups. The current study tested whether MRI predictors of cognition differ in African Americans and Hispanics, compared with non-Hispanic Whites.
Participants were 638 non-demented older adults (29% non-Hispanic White, 36% African American, 35% Hispanic) in the Washington Heights-Inwood Columbia Aging Project. Composite scores of memory, language, speed/executive functioning, and visuospatial function were derived from a neuropsychological battery. Hippocampal volume, regional cortical thickness, infarcts, and white matter hyperintensity (WMH) volumes were quantified with FreeSurfer and in-house developed procedures. Multiple-group regression analysis, in which each cognitive composite score was regressed onto MRI variables, demographics, and cardiovascular health, tested which paths differed across groups.
Larger WMH volume was associated with worse language and speed/executive functioning among African Americans, but not among non-Hispanic Whites. Larger hippocampal volume was more strongly associated with better memory among non-Hispanic Whites compared with Hispanics. Cortical thickness and infarcts were similarly associated with cognition across groups.
The main finding of this study was that certain MRI predictors of cognition differed across racial/ethnic groups. These results highlight the critical need for more diverse samples in the study of cognitive aging, as the type and relation of neurobiological substrates of cognitive functioning may be different for different groups.
To determine the predictive utility of baseline odor identification deficits for future cognitive decline and the diagnosis of Alzheimer disease (AD) dementia.
In a multiethnic community cohort in ...North Manhattan, NY, 1,037 participants without dementia were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). In 757 participants, follow-up occurred at 2 years and 4 years.
In logistic regression analyses, lower baseline UPSIT scores were associated with cognitive decline (relative risk 1.067 per point interval; 95% confidence interval CI 1.040, 1.095; p < 0.0001), and remained significant (relative risk 1.065 per point interval; 95% CI 1.034, 1.095; p < 0.0001) after including covariates. UPSIT, but not Selective Reminding Test-total immediate recall, predicted cognitive decline in participants without baseline cognitive impairment. During follow-up, 101 participants transitioned to AD dementia. In discrete time survival analyses, lower baseline UPSIT scores were associated with transition to AD dementia (hazard ratio 1.099 per point interval; 95% CI 1.067, 1.131; p < 0.0001), and remained highly significant (hazard ratio 1.072 per point interval; 95% CI 1.036, 1.109; p < 0.0001) after including demographic, cognitive, and functional covariates.
Impairment in odor identification was superior to deficits in verbal episodic memory in predicting cognitive decline in cognitively intact participants. The findings support the cross-cultural use of a relatively inexpensive odor identification test as an early biomarker of cognitive decline and AD dementia. Such testing may have the potential to select/stratify patients in treatment trials of cognitively impaired patients or prevention trials in cognitively intact individuals.
•Ambient air pollution is associated with more rapid cognitive decline in older adults.•APOE-ε4 positive individuals had more rapid pollution-associated cognitive decline.•The association was also ...stronger among Non-Hispanic individuals.•No difference in strength of association between age groups, sex, or smoking status.
There is mounting evidence that long-term exposure to air pollution is related to accelerated cognitive decline in aging populations. Factors that influence individual susceptibility remain largely unknown, but may involve the apolipoprotein E genotype E4 (APOE-ε4) allele.
We assessed whether the association between long-term exposure to ambient air pollution and cognitive decline differed by APOE-ε4 status and cognitive risk factors.
The Washington Heights Inwood Community Aging Project (WHICAP) is a prospective study of aging and dementia. Neuropsychological testing and medical examinations occur every 18–24 months. We used mixed-effects models to evaluate whether the association between markers of ambient air pollution (nitrogen dioxide NO2), fine PM2.5, and coarse PM10 particulate matter) and the rate of decline in global and domain-specific cognition differed across strata defined by APOE-ε4 genotypes and cognitive risk factors, adjusting for sociodemographic factors and temporal trends.
Among 4821 participants with an average of 6 years follow-up, higher concentrations of ambient air pollution were associated with more rapid cognitive decline. This association was more pronounced among APOE-ε4 carriers (p < 0.001). A one interquartile range increase in NO2 was associated with an additional decline of 0.09 standard deviations (SD) (95%CI −0.1, −0.06) in global cognition across biennial visits among APOE-ε4 positive individuals and a 0.07 SD (95%CI −0.09, −0.05) decline among APOE-ε4 negative individuals. Results for PM2.5, PM10 and cognitive domains were similar. The association between air pollutants and rate of cognitive decline also varied across strata of race-ethnicity with the association strongest among White non-Hispanic participants.
These results add to the body of evidence on the adverse impact of ambient air pollution on cognitive aging and brain health and provide new insights into the genetic and behavioral factors that may impact individual susceptibility.
The associations between self-reported current and past leisure time physical activity (LTPA) and Alzheimer's disease (AD) incidence were determined using data from the multiethnic ...Washington/Hamilton Heights-Inwood Columbia Aging Project (WHICAP) study.
The metabolic equivalent of LTPA energy expenditure was calculated for self-reported current and past LTPA for 1345 older adults. A Cox proportional hazard model was conducted to estimate the association between LTPA (low, middle, and high) and incident AD risk.
Comparing high to low level, current and past LTPA were both associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.39 (0.20–0.75) and 0.37 (0.18–0.75), respectively. Compared with “always low,” “increased” and “always high” LTPA throughout life were associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.60 (0.36–0.99) and 0.28 (0.08–0.94), respectively. Light- and moderate-intensity LTPA were associated with lower AD risk.
LTPA both throughout life and later in life are associated with lower risk of AD.
•More current and earlier-life LTPA were associated with reduced risk of Alzheimer's disease (AD).•Increasing or maintaining high LTPA throughout life was protective against AD.•Avoiding being physically inactive throughout life was beneficial for prevention of AD.•There was a health benefit in AD prevention by performing light and moderate LTPAs.
Objectives
To determine whether observed hearing loss (OHL) is associated with incident dementia in a multiethnic population.
Design
Prospective epidemiological cohort study.
Setting
Community in ...northern Manhattan.
Participants
Participants in the Washington Heights‐Inwood Columbia Aging Project, a longitudinal study on aging and dementia in an ethnically diverse community (n = 1,881).
Measurements
OHL was defined when the examiner observed it or according to self‐reported hearing aid use. A consensus panel diagnosed dementia using standard research criteria. A Cox proportional hazards model was used to examine the relationship between OHL at baseline and risk of incident dementia (mean 7.3 ± 4.4 years of longitudinal followup, range 0.9–20 years).
Results
OHL was associated with 1.69 (95% confidence interval (CI) = 1.3–2.3, P < .010) times the risk of incident dementia, adjusting for demographic characteristics, cardiovascular risk factors, apolipoprotein E4 genotype, and stroke. When stratified according to race, the association between OHL and incident dementia was high in all groups but was statistically significant only in blacks (hazard ratio = 2.62, 95% CI = 1.5–4.5, P < .010).
Conclusion
OHL was associated with greater risk of incident dementia in a multiethnic cohort. More study is needed to determine whether HL contributes to dementia and whether treating HL can reduce the risk of dementia.
Objective
To examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults.
Methods
Participants were evaluated with the 40‐item ...University of Pennsylvania Smell Identification Test (UPSIT). Follow‐up occurred at 2‐year intervals with information on death obtained from informant interviews and the National Death Index.
Results
During follow‐up (mean = 4.1 years, standard deviation = 2.6), 349 of 1,169 (29.9%) participants died. Participants who died were more likely to be older (p < 0.001), be male (p < 0.001), have lower UPSIT scores (p < 0.001), and have a diagnosis of dementia (p < 0.001). In a Cox model, the association between lower UPSIT score and mortality (hazard ratio HR = 1.07 per point interval, 95% confidence interval CI = 1.05–1.08, p < 0.001) persisted after controlling for age, gender, education, ethnicity, language, modified Charlson medical comorbidity index, dementia, depression, alcohol abuse, head injury, smoking, body mass index, and vision and hearing impairment (HR = 1.05, 95% CI = 1.03–1.07, p < 0.001). Compared to the fourth quartile with the highest UPSIT scores, HRs for mortality for the first, second, and third quartiles of UPSIT scores were 3.81 (95% CI = 2.71–5.34), 1.75 (95% CI = 1.23–2.50), and 1.58 (95% CI = 1.09–2.30), respectively. Participant mortality rate was 45% in the lowest quartile of UPSIT scores (anosmia) and 18% in the highest quartile of UPSIT scores.
Interpretation
Impaired odor identification, particularly in the anosmic range, is associated with increased mortality in older adults even after controlling for dementia and medical comorbidity. Ann Neurol 2015;78:401–411
Periodontitis and Alzheimer disease (AD) are associated with systemic inflammation. This research studied serum IgG to periodontal microbiota as possible predictors of incident AD.
Using a ...case-cohort study design, 219 subjects (110 incident AD cases and 109 controls without incident cognitive impairment at last follow-up), matched on race-ethnicity, were drawn from the Washington Heights-Inwood Columbia Aging Project (WHICAP), a cohort of longitudinally followed northern Manhattan residents aged >65 years. Mean follow-up was five years (SD 2.6). In baseline sera, serum IgG levels were determined for bacteria known to be positively or negatively associated with periodontitis (Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans Y4, Treponema denticola, Campylobacter rectus, Eubacterium nodatum, and Actinomyces naeslundii genospecies-2). In all analyses, we used antibody threshold levels shown to correlate with presence of moderate-severe periodontitis.
Mean age was 72 years (SD 6.9) for controls, and 79 years (SD 4.6) for cases (p<0.001). Non-Hispanic Whites comprised 26%, non-Hispanic Blacks 27%, and Hispanics 48% of the sample. In a model adjusting for baseline age, sex, education, diabetes mellitus, hypertension, smoking, prior history of stroke, and apolipoprotein E genotype, high anti-A. naeslundii titer (>640 ng/ml, present in 10% of subjects) was associated with increased risk of AD (HR = 2.0, 95%CI: 1.1-3.8). This association was stronger after adjusting for other significant titers (HR = 3.1, 95%CI: 1.5-6.4). In this model, high anti-E. nodatum IgG (>1755 ng/ml; 19% of subjects) was associated with lower risk of AD (HR = 0.5, 95%CI: 0.2-0.9).
Serum IgG levels to common periodontal microbiota are associated with risk for developing incident AD.
Abstract Accumulating evidence implicates small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging, in the pathogenesis and ...diagnosis of Alzheimer's disease (AD). Cross-sectional volumetric measures of WMH, particularly in the parietal lobes, are associated with increased risk of AD. In the present study, we sought to determine whether the longitudinal regional progression of WMH predicts incident AD above-and-beyond traditional radiological markers of neurodegeneration (i.e., hippocampal atrophy and cortical thickness). Three hundred three nondemented older adults (mean age = 79.24 ± 5.29) received high-resolution magnetic resonance imaging at baseline and then again 4.6 years (standard deviation = 1.01) later. Over the follow-up interval 26 participants progressed to AD. Using structural equation modeling, we calculated latent difference scores of parietal and nonparietal WMH, hippocampus volumes, and cortical thickness values in AD-related regions. Within the structural equation modeling framework, we determined whether baseline or change scores or both predicted AD conversion, while controlling for several time-invariant relevant variables. Smaller baseline hippocampus volume, change in hippocampus volume (i.e., atrophy), higher baseline parietal lobe WMH, and increasing parietal lobe WMH volume but not WMH in other regions or measures of cortical thickness, independently predicted progression to AD. The findings provide strong evidence that regionally accumulating WMH predict AD onset in addition to hallmark neurodegenerative changes typically associated with AD.
Subjective cognitive decline may reflect a dementia prodrome or modifiable risk factor such as sleep disturbance. What is the association between sleep and subjective cognitive decline? ...Cross‐sectional design, from two studies of older adults: the WHICAP in the USA and the HELIAD in Greece. A total of 1,576 WHICAP and 1,456 HELIAD participants, without mild cognitive impairment, dementia or severe depression/anxiety, were included. Participants were mostly women, with 12 (WHICAP) and 8 (HELIAD) mean years of education. Sleep problems were estimated using the Sleep Scale from the Medical Outcomes Study. Subjective cognitive decline was assessed using a structured complaint questionnaire that queries for subjective memory and other cognitive symptoms. Multinomial or logistic regression models were used to examine whether sleep problems were associated with complaints about general cognition, memory, naming, orientation and calculations. Age, sex, education, sleep medication, use of medications affecting cognition, co‐morbidities, depression and anxiety were used as co‐variates. Objective cognition was also estimated by summarizing neuropsychological performance into composite z‐scores. Sleep problems were associated with two or more complaints: WHICAP: β = 1.93 (95% confidence interval: 1.59–2.34), p ≤ .0001; HELIAD: β = 1.48 (95% confidence interval: 1.20–1.83), p ≤ .0001. Sleep problems were associated with complaints in all the cognitive subcategories, except orientation for the WHICAP. The associations were noted regardless of objective cognition. At any given level of objective cognition, sleep disturbance is accompanied by subjective cognitive impairment. The replicability in two ethnically, genetically and culturally different cohorts adds validity to our results. The results have implications for the correlates, and potential aetiology of subjective cognitive decline, which should be considered in the assessment and treatment of older adults with cognitive complaints.
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. Ann Neurol 2008
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