Age-associated cognitive changes in community dwelling adults

National Institute On Aging

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Abstract

We assessed trends, predictors and outcomes of resource utilization in hospital inpatient discharges with a principal diagnosis of Alzheimer's disease (AD) with at least one procedure. Using Nationwide Inpatient Sample data (NIS, 2002-2012), discharges primarily diagnosed with AD, aged 60 y and with 1 procedure, were selected (Weighted N = 92,300). Hospital resource utilization were assessed using ICD-9-CM codes, while hospitalization outcomes included total charges (TC, 2012$), length of stay (LOS, days), and mortality risk (MR, %). Brain and respiratory or gastrointestinal procedure utilization both dropped annually by 3-7%, while cardiovascular procedures or evaluations, blood evaluations, blood transfusion, and resuscitation (CVD/Blood) as well as neurophysiological and psychological evaluation and treatment (Neuro) procedures increased by 5-8%. Total charges, length of stay, and mortality risk were all markedly higher with use of respiratory or gastrointestinal procedures as opposed to being reduced with use of Brain procedures. Procedure count was positively associated with all three hospitalization outcomes. In sum, patterns of hospital resources that were used among AD inpatients changed over-time, and were associated with hospitalization outcomes such as total charges, length of stay, and mortality risk. The link between longitudinal cognitive change and polymorphisms in the vitamin D receptor (VDR) and MEGALIN or LDL receptor-related protein 2 (LRP2) genes remains unclear, particularly among African-American (AA) adults. We aimed to evaluate associations of single nucleotide polymorphisms (SNPs) for VDR rs11568820 (Cdx-2:T/C), rs1544410 (BsmI:G/A), rs7975232 (ApaI:A/C), rs731236 (TaqI:G/A) and LRP2 rs3755166:G/A,rs2075252:C/T, rs2228171:C/T genes with longitudinal cognitive performance change in various domains of cognition. Data from 1024 AA urban adult participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (Baltimore, Maryland) with complete genetic data were used, of whom 660-797 had complete data on 9 cognitive test scores at baseline or the first follow-up examination and complete covariate data (approximately 52% female; mean age: approximately 52 y; mean years of education: 12.6 y). Time between examination visits 1 (2004-2009) and 2 (2009-2013) ranged from <1 y to approximately 8 y, with a meanSD of 4.640.93 y. Latent class and haplotype analyses were conducted by creating gene polymorphism groups that were related to longitudinal annual rate of cognitive change predicted from mixed-effects regression models. Among key findings, the rs3755166:G/A MEGALIN SNP was associated with faster decline on the Mini-Mental State Examination overall (beta = -0.002, P = 0.018) and among women. VDR2 (BsmI/ApaI/TaqI: G-/A-/A-) SNP latent class SNPLC; compared with VDR1 (ApaI: AA) was linked to faster decline on the Verbal Fluency Test, Categorical, in women, among whom the MEGALIN2 (rs2228171: TT) SNPLC (compared with MEGALIN1:rs2228171: CC) was also associated with a faster decline on the Trailmaking Test, Part B (Trails B), but with a slower decline on the Digit Span Backward (DS-B). Moreover, among men, the VDR1 SNP haplotype (SNPHAP; GCA:baT) was associated with a slower decline on the Trails B, whereas the MEGALIN1 SNPHAP (GCC) was associated with a faster decline on the DS-B, reflected as a faster decline on cognitive domain 2 (visual/working memory). These results suggest VDR and MEGALIN gene variations can alter age-related cognitive trajectories differentially between men and women among AA urban adults, specifically in global mental status and domains of verbal fluency, visual/working memory, and executive function. We also examined interactive relations of race and socioeconomic status (SES) to magnetic resonance imaging (MRI)-assessed global brain outcomes with previously demonstrated prognostic significance for stroke, dementia, and mortality. Participants were 147 African Americans (AAs) and whites (ages 33-71 years; 43% AA; 56% female; 26% below poverty) in the Healthy Aging in Neighborhoods of Diversity across the Life Span SCAN substudy. Cranial MRI was conducted using a 3.0 T unit. White matter (WM) lesion volumes and total brain, gray matter, and WM volumes were computed. An SES composite was derived from education and poverty status. Significant interactions of race and SES were observed for WM lesion volume (b = 1.38; eta = 0.036; p = .028), total brain (b = 86.72; eta = 0.042; p < .001), gray matter (b = 40.16; eta = 0.032; p = .003), and WM (b = 46.56; eta = 0.050; p < .001). AA participants with low SES exhibited significantly greater WM lesion volumes than white participants with low SES. White participants with higher SES had greater brain volumes than all other groups (albeit within normal range). Low SES was associated with greater WM pathology-a marker for increased stroke risk-in AAs. Higher SES was associated with greater total brain volume-a putative global indicator of brain health and predictor of mortality-in whites. Findings may reflect environmental and interpersonal stressors encountered by AAs and those of lower SES and could relate to disproportionate rates of stroke, dementia, and mortality.