Meta-Analysis of White Matter Hyperintensity Volume Differences Between APOE ε4 Carriers and Noncarriers.

Several studies have suggested that white matter hyperintensity volume (WMHV) is increased among apolipoprotein E (APOE) ε4 carriers while others have reported contradictory findings. Although APOE ε4 carriage is associated with greater AD pathology, it remains unclear whether cerebrovascular damage is also associated with APOE ε4 carriage. The aim of this meta-analysis was to determine whether WMHV is associated with APOE ε4 carrier status. 12 studies that were included yielded a total sample size of 16,738 adult subjects (ε4 carrier n = 4,721; ε4 noncarrier n = 12,017). There were no significant differences in WMHV between ε4 carriers and noncarriers (Hedge's g = 0.07; 95% CI (-0.01 to 0.15), P = 0.09). Subgroup analysis of community-based studies (n = 8) indicated a small effect size where ε4 carriers had greater WMHV relative to noncarriers (Hedge's g = 0.09 95% CI (0.02 to 0.16), P = 0.008). Among clinic-based studies (n = 3) there was no significant difference in WMHV by APOE ε4 carrier status (Hedge's g = -0.09, 95% CI (-0.60 to 0.41), P = 0.70). Observed APOE ε4-associated WMHV differences may be context-dependent and may also be confounded by a lack of standardization for WMHV segmentation.

Meta-Analysis of Animal Fluency Performance in Amnestic Mild Cognitive Impairment and Cognitively Unimpaired Older Adults.

Animal fluency is a commonly used neuropsychological measure that is used in the diagnosis of amnestic mild cognitive impairment (aMCI) and Alzheimer disease. Although most individuals with aMCI have clinically normal scores on this test, several studies have shown that aMCI individuals' performance is significantly lower than that of cognitively unimpaired (CU) individuals. The aim of this meta-analysis was to characterize the effect size of animal fluency performance differences between aMCI and CU individuals. Literature search with search terms used were: "animal fluency and mild cognitive impairment," "semantic fluency and mild cognitive impairment," "category fluency and mild cognitive impairment." Both the standardized mean difference and the raw mean difference were derived from random effects analyses. Demographically adjusted z-scores for animal fluency performance for the aMCI groups were obtained to determine normative performance. Nineteen studies were included in the analysis. The standardized mean difference for animal fluency performance between CU and aMCI was 0.89 (95% confidence interval: [0.73; 1.04], P <0.001), I2 =70.3% [52.7%; 81.4%], which reflects a large effect size with moderate heterogeneity. The raw mean difference was -4.08 [-4.75; -3.38], P <0.001. The mean animal fluency z-score for aMCI groups was in the Low Average range (z=-0.77). This study found a substantial difference in animal fluency performance between aMCI and CU individuals. The aMCI groups' normative performance did not fall into the impaired range, indicating that there are important subclinical differences in animal fluency performance that may inform the design of cognitive end points for Alzheimer's disease prevention trials.

A public resource of baseline data from the Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial.

INTRODUCTION: The Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Trial evaluated the anti-oligomeric amyloid beta (Aß) antibody therapy crenezumab in cognitively unimpaired members of the Colombian presenilin 1 (PSEN1) E280A kindred. We report availability, methods employed to protect confidentiality and anonymity of participants, and process for requesting and accessing baseline data. METHODS: We developed mechanisms to share baseline data from the API ADAD Trial in consultation with experts and other groups sharing data from Alzheimer's disease (AD) prevention trials, balancing the need to protect anonymity and trial integrity with making data broadly available to accelerate progress in the field. We pressure-tested deliberate and inadvertent potential threats under specific assumptions, employed a system to suppress or mask both direct and indirect identifying variables, limited and firewalled data managers, and put forth specific principles requisite to receive data. RESULTS: Baseline demographic, PSEN1 E280A and apolipoprotein E genotypes, florbetapir and fluorodeoxyglucose positron emission tomography, magnetic resonance imaging, clinical, and cognitive data can now be requested by interested researchers. DISCUSSION: Baseline data are publicly available; treatment data and biological samples, including baseline and treatment-related blood-based biomarker data will become available in accordance with our original trial agreement and subsequently developed Collaboration for Alzheimer's Prevention principles. Sharing of these data will allow exploration of important questions including the differential effects of initiating an investigational AD prevention therapy both before as well as after measurable Aß plaque deposition.

Neuropathologic validation of the Alzheimer's Questionnaire.

The Alzheimer's Questionnaire (AQ) is an informant-based screening tool with good diagnostic accuracy for Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). The aim of this study is to validate the AQ with AD-associated neuritic plaque (NP) and neurofibrillary tangle (NFT) pathology. Data from 205 prospectively followed autopsy cases clinically classified as AD (n = 90), aMCI (n = 42), or cognitively unimpaired (CU, n = 73) were used. Semi-quantitative measures of NP and NFT pathology were correlated with the AQ, Clinical Dementia Rating Sum of Boxes (CDR-SOB), and the Mini-Mental State Exam (MMSE). The AQ correlated significantly (p < 0.001) with NP load (r = 0.37) and NFT load (r = 0.57). The MMSE and CDR-SOB showed similar correlations with NP load (r = - 0.37, r = 0.35, respectively) and NFT load (r = - 0.58, r = 0.55, respectively). The AQ correlates well with NP and NFT pathology of AD, which provides additional confidence to clinicians using the AQ to screen for AD-related cognitive impairment.

Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer's disease carriers and non-carriers: Baseline findings from the API ADAD Colombia Trial.

INTRODUCTION: Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers. METHODS: We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing. RESULTS: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory. DISCUSSION: Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience.

Telomeric alterations in the default mode network during the progression of Alzheimer's disease: Selective vulnerability of the precuneus.

AIMS: Although telomere length (TL) and telomere maintenance proteins (shelterins) are markers of cellular senescence and peripheral blood biomarkers of Alzheimer's disease (AD), little information is available on telomeric alterations during the prodromal stage (MCI) of AD. We investigated TL in the default mode network (DMN), which underlies episodic memory deficits in AD, as well as shelterin protein and mRNA levels in the precuneus (PreC). METHODS: Telomere length was evaluated in DMN hubs and visual cortex using quantitative PCR (qPCR). In the PreC, western blotting and NanoString nCounter expression analyses evaluated shelterin protein and mRNA levels, respectively, in cases with an antemortem clinical diagnosis of no cognitive impairment (NCI), MCI and AD. RESULTS: TL was significantly reduced in the PreC in MCI and AD compared to NCI, but stable in frontal, inferior temporal, posterior cingulate and visual cortex. PreC TL correlated significantly with performance on cognitive tests. NCI cases with high vs low Braak scores displayed significantly shorter TL in posterior cingulate and frontal cortex, which correlated significantly with neuritic and diffuse amyloid-ß plaque counts. Shelterin protein levels (TIN2, TRF1, TRF2 and POT1) declined in MCI and AD compared to NCI. The PreC displayed stable expression of shelterins TERF1, TERF2, POT1, RAP1 and TPP1, while TINF2 mRNA significantly increased in AD compared to NCI. CONCLUSIONS: These findings indicate a selective vulnerability to telomere attrition within different nodes of the DMN in prodromal AD and in aged NCI individuals with high Braak scores highlighting a putative role in the pathogenesis of AD.

Challenging the relationship of grip strength with cognitive status in older adults.

OBJECTIVE: Grip strength is a widely used motor assessment in ageing research and has repeatedly been shown to be associated with cognition. It has been proposed that grip strength could enhance cognitive screening in experimental or clinical research, but this study uses multiple data-driven approaches to caution against this interpretation. Furthermore, we introduce an alternative motor assessment, comparable to grip dynamometry, but has a more robust relationship with cognition among older adults. DESIGN: Associations between grip strength and cognition (measured with the Montreal Cognitive Assessment) were analysed cross sectionally using multivariate regression in two datasets: (1) The Irish LongituDinal Study on Ageing (TILDA; N = 5,980, community-dwelling adults ages 49-80) and (2) an experimental dataset (N = 250, community-dwelling adults aged 39-98). Additional statistical simulations on TILDA tested how ceiling effects or skewness in these variables influenced these associations for quality control. RESULTS: Grip strength was significantly but weakly associated with cognition, consistent with previous studies. Simulations revealed this was not due to skewness/ceiling effects. Conversely, a new alternative motor assessment (functional reaching [FR]) had a stronger, more robust and more sensitive relationship with cognition compared to grip strength. CONCLUSIONS: Grip strength should be cautiously interpreted as being associated with cognition. However, FR may have a stronger and clinically useful relationship with cognition.

Norms and equivalences for MoCA-30, MoCA-22, and MMSE in the oldest-old.

BACKGROUND: Cognitive screening is important for the oldest-old (age 90 +). This age group is the fastest growing and has the highest risk of dementia. However, norms and score equivalence for screening tests are lacking for this group. AIMS: To provide norms and score equivalence for commonly used cognitive screening tests for the oldest-old. METHODS: Data on 157 participants of the Center for Healthy Aging Longevity Study aged 90 + were analyzed. First, we derived norms for (1) subtests and cognitive domains of the in-person Montreal Cognitive Assessment having a maximum score of 30 (MoCA-30) and (2) the total MoCA-22 score, obtained from the in-person MoCA-30 by summing the subtests that do not require visual input to a maximum score of 22. These norms were derived from 124 participants with a Mini-Mental State Examination (MMSE) ≥ 27. Second, we derived score equivalences for MMSE to MoCA-30 and MoCA-22, and MoCA-30 to MoCA-22 using equipercentile equating method with log-linear smoothing, based on all 157 participants. RESULTS: MoCA-22 total score norms are: mean = 18.3(standard deviation = 2.2). An MMSE score of 27 is equivalent to a MoCA-30 score of 22 and a MoCA-22 score of 16. DISCUSSION AND CONCLUSIONS: Subtest, domain and MoCA-22 norms will aid in evaluation of the oldest-old who cannot complete the MoCA-30 or are tested over the phone. The equivalences of the three cognitive tests (MMSE, MoCA-30, MoCA-22) in the oldest-old will facilitate continuity of cognitive tracking of individuals tested with different tests over time and comparison of the studies that use different cognitive tests.

Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer's disease.

BACKGROUND: Chitinase 3-like 1 (CHI3L1), chitinase 3-like 2 (CHI3L2), and neuronal pentraxin II (NPTX2) are inflammatory biomarkers of Alzheimer's disease (AD). Although studies have demonstrated that cerebrospinal fluid levels of these proteins are changed in AD, no studies have undertaken a detailed examination of alterations in protein levels, cellular expression, and interaction with amyloid in the brain during the progression of AD. METHODS: The study evaluated levels of both CHI3L1 and CHI3L2, NPTX2, ionized calcium-binding adapter molecule 1 (Iba1), complement component 1q (C1q), glial fibrillary acidic protein (GFAP), and CD44, in the frontal cortex of people who died with an antemortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD (mAD), and severe AD (sAD) using immunoblot and immunohistochemical techniques. RESULTS: CHI3L1-immunoreactive (-ir) astrocyte numbers were increased in the frontal cortex and white matter in sAD compared to NCI. On the other hand, increases in GFAP and Iba1-ir cell numbers were observed in MCI compared to NCI but only in white matter. Western blot analyses revealed significantly lower frontal cortex CHI3L2 levels, whereas CD44 levels were increased in sAD. No significant differences for CHI3L1, GFAP, C1q, and NPTX2 protein levels were detected between clinical groups. Strong significant correlations were found between frontal cortex CHI3L1 and Iba1-ir cell numbers in white matter and CHI3L1 and C1q protein levels in the early stages of the disease. C1q and Iba1, CD44 with CHI3L2, and GFAP protein levels were associated during disease progression. CHI3L1 and Iba1 cell numbers in white matter showed a significant associations with episodic memory and perceptual speed. CONCLUSIONS: White matter CHI3L1 inflammatory response is associated with cognitive impairment early in the onset of AD.

Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal-Dominant Alzheimer's Disease Colombia Trial.

INTRODUCTION: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo-controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60-year-old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non-carriers who receive placebo. METHODS: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non-carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. RESULTS: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non-carriers, 30 to 53 years of age. Carriers were significantly younger than non-carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. DISCUSSION: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non-carriers. Their demographic characteristics are representative of the local population.

Brain-derived neurotrophic factor (BDNF) and TrkB hippocampal gene expression are putative predictors of neuritic plaque and neurofibrillary tangle pathology.

INTRODUCTION: Downregulation of brain-derived neurotrophic factor (BDNF) and its cognate neurotrophin receptor, TrkB, were observed during the progression of dementia, but whether the Alzheimer's disease (AD) pathological lesions diffuse plaques, (DPs), neuritic plaques (NPs), and neurofibrillary tangles (NFTs) are related to this alteration remains to be clarified. METHODS: Negative binomial (NB) regressions were performed using gene expression data accrued from a single population of CA1 pyramidal neurons and regional hippocampal dissections obtained from participants in the Rush Religious Orders Study (RROS). RESULTS: Downregulation of Bdnf is independently associated with increased entorhinal cortex NPs. Downregulation of TrkB is independently associated with increased entorhinal cortex NFTs and CA1 NPs during the progression of AD. DISCUSSION: Results indicate that BDNF and TrkB dysregulation contribute to AD neuropathology, most notably hippocampal NPs and NFTs. These data suggest attenuating BDNF/TrkB signaling deficits either at the level of BDNF, TrkB, or downstream of TrkB signaling may abrogate NPs and/or NFTs.

Selective decline of neurotrophin and neurotrophin receptor genes within CA1 pyramidal neurons and hippocampus proper: Correlation with cognitive performance and neuropathology in mild cognitive impairment and Alzheimer's disease.

Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom-designed microarray analysis, and qPCR of CA1 subregional dissections. Gene expression levels were correlated with cognitive test scores and AD neuropathology criteria. We found a significant downregulation of several neurotrophin genes (e.g., Gdnf, Ngfb, and Ntf4) in CA1 pyramidal neurons in MCI compared to NCI and AD subjects. In addition, the neurotrophin receptor transcripts TrkB and TrkC were decreased in MCI and AD compared to NCI. Regional hippocampal dissections also revealed select neurotrophic gene dysfunction providing evidence for vulnerability within the hippocampus proper during the progression of dementia. Downregulation of several neurotrophins of the NGF family and cognate neurotrophin receptor (TrkA, TrkB, and TrkC) genes correlated with antemortem cognitive measures including the Mini-Mental State Exam (MMSE), a composite global cognitive score (GCS), and Episodic, Semantic, and Working Memory, Perceptual Speed, and Visuospatial domains. Significant correlations were found between select neurotrophic expression downregulation and neuritic plaques (NPs) and neurofibrillary tangles (NFTs), but not diffuse plaques (DPs). These data suggest that dysfunction of neurotrophin signaling complexes have profound negative sequelae within vulnerable hippocampal cell types, which play a role in mnemonic and executive dysfunction during the progression of AD.

Frontal cortex and striatal cellular and molecular pathobiology in individuals with Down syndrome with and without dementia.

Although, by age 40, individuals with Down syndrome (DS) develop amyloid-ß (Aß) plaques and tau-containing neurofibrillary tangles (NFTs) linked to cognitive impairment in Alzheimer's disease (AD), not all people with DS develop dementia. Whether Aß plaques and NFTs are associated with individuals with DS with (DSD +) and without dementia (DSD -) is under-investigated. Here, we applied quantitative immunocytochemistry and fluorescent procedures to characterize NFT pathology using antibodies specific for tau phosphorylation (pS422, AT8), truncation (TauC3, MN423), and conformational (Alz50, MC1) epitopes, as well as Aß and its precursor protein (APP) to frontal cortex (FC) and striatal tissue from DSD + to DSD - cases. Expression profiling of single pS422 labeled FC layer V and VI neurons was also determined using laser capture microdissection and custom-designed microarray analysis. Analysis revealed that cortical and striatal Aß plaque burdens were similar in DSD + and DSD - cases. In both groups, most FC plaques were neuritic, while striatal plaques were diffuse. By contrast, FC AT8-positive NFTs and neuropil thread densities were significantly greater in DSD + compared to DSD -, while striatal NFT densities were similar between groups. FC pS422-positive and TauC3 NFT densities were significantly greater than Alz50-labeled NFTs in DSD + , but not DSD - cases. Putaminal, but not caudate pS422-positive NFT density, was significantly greater than TauC3-positive NFTs. In the FC, AT8 + pS422 + Alz50, TauC3 + pS422 + Alz50, pS422 + Alz50, and TauC3 + pS422 positive NFTs were more frequent in DSD + compared to DSD- cases. Single gene-array profiling of FC pS422 positive neurons revealed downregulation of 63 of a total of 864 transcripts related to Aß/tau biology, glutamatergic, cholinergic, and monoaminergic metabolism, intracellular signaling, cell homeostasis, and cell death in DSD + compared DSD - cases. These observations suggest that abnormal tau aggregation plays a critical role in the development of dementia in DS.

Trajectory and variability characterization of the Montreal cognitive assessment in older adults.

BACKGROUND: The Montreal cognitive assessment (MoCA) has become one of the most widely used cognitive screening instruments since its initial publication. To date, only a handful of studies have explored longitudinal characteristics of the MoCA. AIM: The aim of this study is to characterize the trajectory of MoCA performance across a broad age continuum of older adults. METHODS: Data from 467 cognitively normal participants were used in this analysis. The sample was grouped into four strata based on the participants' age at baseline (60-69, 70-79, 80-89, and 90-99). Mixed model repeated measures (MMRM) analysis and mixed-effects spline models were used to characterize the trajectory of MoCA scores in each age stratum and in the entire sample. Intrasubject standard deviation (ISD) was used to characterize the natural variability of individual MoCA performance over time. RESULTS: The ISD values for each of the age strata indicated that year-to-year individual variation on the MoCA ranged from zero to three points. MMRM analysis showed that the 60-69 stratum remained relatively stable over time while the 70-79 and 80-89 strata both showed notable decline relative to baseline performance. The mixed-effects spline model showed that MoCA performance declines linearly across the older adult age span. DISCUSSION: Among cognitively normal older adults MoCA performance remains relatively stable over time, however across the older adult age-span MoCA performance declines in a linear fashion. These results will help clinicians better understand the normal course of MoCA change in older adults while researchers may use these results to inform sample size estimates for intervention studies. CONCLUSION: This study provides an enhanced view of the MoCA's intraindividual trajectory in normal elderly aged 60 and older.

Frontal Cortex and Hippocampal γ-Secretase Activating Protein Levels in Prodromal Alzheimer Disease.

BACKGROUND: ß-Amyloid (Aß) is the product of concerted cleavage of the amyloid precursor protein (APP) by ß- and γ-secretases. However, the molecular mechanisms that regulate this process are not well understood. Recently, evidence was reported that γ-secretase activating protein (GSAP, 16 kDa), derived from a larger precursor protein (98 kDa), plays a role in Aß metabolism through a mechanism involving its interaction with both γ-secretase and APP. However, a detailed evaluation of GSAP protein levels and their association with clinical and neuropathological variables are lacking during the clinical progression of Alzheimer disease (AD). METHODS: We quantified levels of the GSAP precursor (98 kDa) and its active form (16 kDa) in the frontal cortex and hippocampus, areas displaying extensive Aß and neurofibrillary tangle (NFT) pathology, in subjects who came to autopsy with a premortem clinical diagnosis of noncognitive impairment, mild cognitive impairment, mild to moderate AD, and severe AD using Western blotting. RESULTS: Analysis found that 98-kDa GSAP levels were increased, while those of 16 kDa were reduced in the frontal cortex of severe-AD subjects. By contrast, GSAP levels remained stable in the hippocampus. Frontal cortex and hippocampal GSAP 98- and 16-kDa levels were not associated with Aß, NFT, and neuropathological criteria across clinical groups. Interestingly, only neocortical 98-kDa GSAP values showed a significant correlation with the Mini-Mental State Examination and episodic memory scores. CONCLUSIONS: These data demonstrate that GSAP proteins are differentially dysregulated in severe AD, but only the full-length form was associated with cognitive test scores in AD.

Reversion From Mild Cognitive Impairment to Normal Cognition: A Meta-Analysis.

The initiation of Alzheimer disease (AD) prevention studies has placed greater emphasis on the need to accurately detect individuals with amnestic mild cognitive impairment (aMCI) given their increased risk for developing AD. Several studies reporting on the incidence and prevalence of aMCI have also found that a substantial number of aMCI cases at baseline assessments revert to normal cognition at subsequent assessments. This instability presents a major challenge to intervention studies aimed at preventing the onset of clinical symptoms associated with aMCI. Reversion rates from 25 studies were used for this meta-analysis which found an overall reversion rate of approximately 24%. When the studies were separated by their setting (community vs. clinic), substantial differences in reversion rates were noted with clinic-based studies having a much lower reversion rate (14%) than community-based studies (31%). North American and European studies had high heterogeneity of reversion rates, whereas Asian studies had moderate levels of heterogeneity and significantly lower rates of reversion. Continued improvement in diagnostic and classification methodologies may help in more accurately identifying aMCI cases which are less likely to revert to normal cognition.

A Cross-Sectional Analysis of Late-Life Cardiovascular Factors and Their Relation to Clinically Defined Neurodegenerative Diseases.

Studies have demonstrated associations between cardiovascular factors and Alzheimer disease (AD) with minimal focus on other neurodegenerative diseases. Utilizing cross-sectional data from 17,532 individuals in the National Alzheimer's Coordinating Center, Uniform Data Set, we compared the presence of cardiovascular factors [body mass index (BMI), atrial fibrillation, hypertension, hyperlipidemia, and diabetes] in individuals carrying a diagnosis of Probable AD (ProbAD), Possible AD, vascular dementia, dementia with Lewy bodies (DLB), frontotemporal dementia, Parkinson disease, progressive supranuclear palsy, or corticobasal degeneration, with that of normals. Generalized linear mixed models were fitted with age at visit, gender, and cardiovascular factors as fixed effects and Alzheimer's Disease Centers as random effects. In late life, only BMI of ProbAD and DLB patients was statistically significantly lower than that in normals (P-values <0.001). When accounting for colinearity within cardiovascular factors, a low BMI was a comorbidity of certain dementia etiologies as compared with normals. These data support a concept of disease-specific associations with certain cardiovascular factors.

Description and cohort characterization of the Longevity Study: learning from our elders.

The purpose of this article is to describe the Longevity Study: Learning From Our Elders, a research program on healthy aging that began in 2007 at the Center for Healthy Aging at Banner Sun Health Research Institute. As of June 2015, 1139 participants (age range of 50-110 years) completed baseline assessments with the majority living in the Sun Cities retirement communities northwest of Phoenix, Arizona but expanding throughout the state. The registry includes over 830 currently active participants with 450 aged 80 years and older, 188 aged 90 and older, and 27 centenarians. Data from in-person interviews at the Center for Healthy Aging in Sun City or in the participants' residences which includes sociodemographic, medical, cognitive, physical and psychosocial variables have been collected since the study's inception. This paper outlines some of the key demographic and clinical characteristics of the Longevity Study, its progress, and future directions. It also reflects on how exceptional aging individuals function psychosocially, cognitively and physically, particularly among individuals aged 85 and older.

Longer self-reported sleep duration is associated with decreased performance on the montreal cognitive assessment in older adults.

BACKGROUND: Previous studies investigating the relationship between sleep duration and cognitive function in older adults have suggested that longer sleep durations are associated with decreased cognitive performance. AIM: The intent of this study is to determine if performance on the Montreal Cognitive Assessment (MoCA) and the Mini Mental State Exam (MMSE) is associated with self-reported sleep duration in older adults. METHODS: Data from 189 cognitively normal older adults aged 75 and older (mean age 89.29 ± 7.62) and free of severe depression were used for this analysis. Individuals were grouped based on their self-reported hours of sleep (short duration = <7, normal duration = 7, >9, and long duration = ≥9). The Kruskal-Wallis test was used to discern group differences on the MoCA scores, while multinomial logistic regression was used to assess the association between MoCA and MMSE scores and sleep group. RESULTS: The long duration group had significantly lower MoCA scores than the normal duration group (p = 0.02). The short duration group was not significantly different from the normal duration group (p = 0.33). Individuals in the short duration group were more likely to have higher MoCA scores than those in long duration group after adjusting for age, gender, and presence of depressive symptoms [OR 0.86, 95 % CI (0.76, 0.98), p = 0.02]. CONCLUSION: The results of this study suggest that in a group of non-demented, very old subjects, self-reported sleep duration of nine or more hours is associated with decreased cognitive performance on the MoCA in older adults, even after accounting for age, gender, and presence of depressive symptoms.

Cognitive Function as a Mediator in the Relationship Between Physical Activity and Depression Status in Older Adults.

Previous research has found that increased physical activity may provide a protective effect on depression status; however, these studies do not account for cognitive function. This study's aim was to determine whether cognitive function mediates the association between physical activity depression status in older adults. Data from 501 older adults were used for this analysis. Physical activity had a significant protective effect on depression (OR = 0.761, 95% CI [0.65, 0.89], p = .001). Adjusted analysis yielded an attenuated association (OR = 0.81, 95% CI [0.69, 0.95], p = .01) with a significant interaction for physical activity and cognitive function (OR = 0.991, 95% CI [0.985, 0.997], p = .005). MoCA performance also had a significant mediating effect on the relationship between physical activity and depression status (p = .04). These findings suggest that cognitive function is associated with, and does mediate, the relationship between physical activity and depression status.