Statin use moderates APOE's and CRP's associations with dementia and is associated with lesser dementia severity in ε4 carriers.

INTRODUCTION: We tested the effect of statins on C-reactive protein (CRP) and apolipoprotein E (APOE)'s associations with dementia severity. METHODS: A total of 1725 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assigned from 12-month follow-up data into the following groups: (1) ε4 (-)/statin (-), (2) ε4 (-)/statin (+), (3) ε4 (+)/statin (-), and (4) ε4 (+)/statin (+). Dementia severity was assessed by a δ homolog: "dHABS." A mediation model was stratified on statin use and moderation effects tested by a chi-square difference. RESULTS: Plasma CRP level decreased with ε4 allelic dose. Statins had no effect on the dHABS d-score in non-carriers but were associated with better scores in carriers. Treated carriers did not have more severe dementia than non-carriers. Statin use moderated the mutual adjusted effects of APOE and CRP. CRP was not a mediator of APOE's effect. DISCUSSION: Statins may provide a protective effect on the dementia severity of ε4 carriers. HIGHLIGHTS: δ is a dementia-specific phenotype related to general intelligence "g" and is assessed via a "d-score." Apolipoprotein E (APOE) and plasma C-reactive protein (CRP) are independently associated with δ. Plasma CRP decreases with ε4 allelic dose. Statins were associated with better (less demented) d-scores in ε4 carriers but had no effect in non-ε4 carriers. Treated ε4 carriers did not have more severe dementia than non-carriers. Statin use moderated the effects of APOE and CRP on δ. CRP was not a mediator of APOE's effect on δ.

δ scores predict multiple neuropsychiatric symptoms.

OBJECTIVES: Dementia severity is strongly related to Spearman's general intelligence factor "g", via the latent dementia phenotype "δ" and is distinct from domain-specific cognitive impairments arising from disease-specific regional pathologies. It is an empiric question whether behavioral and psychological symptoms of dementia (BPSD) are associated with δ or with domain-specific constructs. METHODS: A recently developed δ homolog ("dDx") was tested as a predictor of 1 year prospective BPSD in n = 723 Mexican-American and non-Hispanic White participants in the Texas Alzheimer's Research and Care Consortium (TARCC). The informant-rated frequencies of 12 BPSD were rated by the neuropsychiatric inventory (NPI-Q). Baseline BPSD, demographic features, selected biomarkers, and treatment exposure to acetylcholinesterase inhibitors were used as covariates. Composite scores derived from orthogonal latent measures of domain-specific memory (MEM) and executive function (EF) were also tested as predictors. RESULTS: "Functionally salient cognitive impairment (FSCI)" that is, categorical "dementia" as diagnosed by dDx was associated with increased prospective frequency of 11/12 BPSD, independently of baseline behavior and covariates. Age, depressive symptoms, and EF were associated with individual BPSD. MEM was not associated with any. Dementia severity, as measured by dDx, was also associated with a prospective increase in total NPI-Q scores. CONCLUSION: δ is associated non-specifically with multiple BPSD. This suggests the existence of a dementia-specific behavioral profile, arising from insults to general intelligence, and unrelated to disease-specific regional pathology(ies).

Construction of a Potential Telephone Assessment of Dementia Prevalence and Severity.

The "δ" (for "dementia") is a latent dementia phenotype that can be constructed by a unique confirmatory bifactor model in a structural equation model framework. Because it is derived from Spearman's general intelligence factor, "g," δ can be constructed from any cognitive battery. This may allow for accurate dementia case-finding by telephone and in the absence of expert clinical evaluation or review. The authors constructed a new δ homolog in a large ethnically diverse convenience sample: the Texas Alzheimer's Research and Care Consortium, comprising 2,016 participants (Alzheimer's disease [AD], N=920; mild cognitive impairment, N=277; normal controls, N=819). A δ composite ("dTEL") was extracted from informant-rated Instrumental Activities of Daily Living and a brief battery of verbal cognitive measures. The entire battery was engineered to be administered over the telephone. dTEL's model had excellent fit. dTEL correlated strongly with dementia severity, as measured by the Clinical Dementia Rating "sum of boxes" scale (r=0.78, p<0.001). The dTEL composite's area under the receiver operating characteristic curve for the discrimination between control subjects and AD patients was 0.97 (95% CI=0.964-0.975). This was superior to all dTEL indicators. Therefore, the authors have demonstrated that a δ homolog composite constructed entirely from verbal measures is strongly associated with dementia severity, can accurately diagnose dementia, and outperforms all observed measures from which it is constructed. Future studies are required to assess dTEL's performance relative to evaluation by expert clinicians when obtained by lay psychometricians over the telephone.

Clock Copying Predicts Mortality in Adult Protective Services Clients.

OBJECTIVE: The objective of this study was to determine if a clock copying task predicts 18-month mortality in an Adult Protective Services (APS) sample referred for a decision-making capacity assessment. METHODS: The authors performed a retrospective medical record review of clients (N = 233) referred by APS for a decision-making capacity assessment during a 3-year time period. Information extracted included demographic data and neuropsychological performance on a battery sensitive to executive function, visuospatial ability, depression, memory, and general cognition. A Cox proportional hazards models was constructed to determine the relationship between Executive Clock Drawing Task Part 2 (CLOX2) performance and survival. RESULTS: Poor clock copying, as measured by CLOX2, predicted 18-month mortality when covaried for age, education, sex, rural dwelling status, depression, and general cognition. CONCLUSIONS: Clock copying is an easily administered visuospatial task that may inform survival in this vulnerable population.

Cross-Ethnic Differences in the Severity of Neuropsychiatric Symptoms in Persons With Mild Cognitive Impairment and Alzheimer's Disease.

In this cross-sectional study, we examined the neuropsychiatric profile of mild cognitive impairment (MCI) and Alzheimer's disease (AD) using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Data were available on 875 controls, 339 MCI cases, and 975 AD participants. Surprisingly, differences in neuropsychiatric symptom (NPS) severity by ethnicity in subjects with AD, but not with MCI, were found. More so, in Hispanics with AD, a higher frequency in most of the individual NPI-Q symptom items of the scale was observed, except for apathy. After adjustment for clinical features, some individual NPI-Q symptoms also showed an association with Hispanic ethnicity in the control group that nearly reached statistical significance. There may be cross-ethnic differences in the neuropsychiatric presentation of AD in Hispanics versus non-Hispanic whites. Future studies are needed to clarify the etiology of these differences, and to assess the need for ethnicity-specific treatment and care-giving interventions.

Neuropsychiatric symptoms in community-dwelling Mexican-Americans: results from the Hispanic Established Population for Epidemiological Study of the Elderly (HEPESE) study.

OBJECTIVE: The Neuropsychiatric Inventory (NPI) is a well-established measure of psychopathology and frequently used in dementia studies. Little is known about its psychometric characteristics at a population level, particularly among Hispanics. We report the frequency of NPI symptoms in a community-dwelling older Mexican-American (MA) population cohort and the degree of symptom-related distress experienced by participant informants. METHODS: Participants were 1079 MA age 80 years and over residing in five southwestern states who were administered the NPI as part of wave-7 of the Hispanic Established Population for Epidemiological Study of the Elderly (HEPESE) conducted from 2010 to 2011. RESULTS: Nine hundred twenty-five informants rated NPI domains. Prevalence of neuropsychiatric symptoms (NPS) varied by symptom domain and ranged from agitation/aggression (32%) to euphoria/elation (5%). The overall rate of behavioral disturbances was 62.7%. On the other hand, 37.3% of informants reported no NPS. A significant fraction of the informants reported distress from the mood disorder cluster of the scale. CONCLUSIONS: A large percentage (>60%) of community-dwelling older MA have one or more informant-reported NPS. These symptoms have diagnostic, prognostic, and therapeutic implications. Although neuropsychiatric disorders may be the initial clinical manifestation of dementia and often appear before cognitive alterations, the high frequency of these symptoms in the HEPESE cohort may reflect a high prevalence of these disorders among community-dwelling MA. The pattern we observed also suggests relatively advanced stages of dementia.

Latent variables may be useful in pain's assessment.

BACKGROUND: Unobserved "latent" variables have the potential to minimize "measurement error" inherent to any single clinical assessment or categorical diagnosis. OBJECTIVES: To demonstrate the potential utility of latent variable constructs in pain's assessment. DESIGN: We created two latent variables representing depressive symptom-related pain (Pd) and its residual, "somatic" pain (Ps), from survey questions. SETTING: The Hispanic Established Population for Epidemiological Studies in the Elderly (H-EPESE) project, a longitudinal population-based cohort study. PARTICIPANTS: Community dwelling elderly Mexican-Americans in five Southwestern U.S. states. The data were collected in the 7th HEPESE wave in 2010 (N = 1,078). MEASUREMENTS: Self-reported pain, Center for Epidemiological Studies Depression Scale (CES-D) scores, bedside cognitive performance measures, and informant-rated measures of basic and instrumental Activities of Daily Living. RESULTS: The model showed excellent fit [χ2 = 20.37, DF = 12; p = 0.06; Comparative fit index (CFI) = 0.998; Root mean statistical error assessment (RMSEA) = 0.025]. Ps was most strongly indicated by self-reported pain-related physician visits (r = 0.48, p ≤0.001). Pd was most strongly indicated by self-reported pain-related sleep disturbances (r = 0.65, p <0.001). Both Pd and Ps were significantly independently associated with chronic pain (> one month), regional pain and pain summed across selected regions. Pd alone was significantly independently associated with self-rated health, life satisfaction, self-reported falls, Life-space, nursing home placement, the use of opiates, and a variety of sleep related disturbances. Ps was associated with the use of NSAIDS. Neither construct was associated with declaration of a resuscitation preference, mode of resuscitation preference declaration, or with opting for a "Do Not Resuscitate" (DNR) order. CONCLUSION: This analysis illustrates the potential of latent variables to parse observed data into "unbiased" constructs with unique predictive profiles. The latent constructs, by definition, are devoid of measurement error that affects any subset of their indicators. Future studies could use such phenotypes as outcome measures in clinical pain management trials or associate them with potential biomarkers using powerful parametric statistical methods.

Telephone screening for mild cognitive impairment in hispanics using the Alzheimer's questionnaire.

UNLABELLED: BACKGROUND/STUDY CONTEXT: There is a need for a simple and reliable screening test to detect individuals with mild cognitive impairment (MCI). The authors analyzed the relationship between performance of the Alzheimer's Questionnaire (AQ), an informant-rated measure of dementia-related behaviors, relative to the Telephone Interview for Cognitive Status-modified (TICS-m), Memory Impairment Scale-telephone version (MIS-t), and the Telephone Executive Assessment (TEXAS) as predictors of MCI. METHODS: Comparative cross-sectional design, with data collected from participants in the Texas Alzheimer's Research and Care Consortium's (TARCC) San Antonio site. One-hundred percent of our sample was Hispanic. The San Antonio subset of TARCC sample is highly enriched with Mexican Americans (MAs). Fifty-five percent of the interviews were conducted in Spanish. Of the 184 persons enrolled, 124 were normal controls (NCs), and 60 participants had MCI. MCI status and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) were determined through clinical consensus and performed blind to telephone assessments. Controlling for age, gender, education, and language of interview, the association between telephone measures and CDR-SOB was evaluated by multivariate regression. RESULTS: AQ scores were not affected by education, gender, and language of interview, but subject's age did show a positive correlation with informant AQ ratings. The AQ predicted CDR-SOB independently of the cognitive measures, adding variance above and beyond demographics. The TICS-m and the TEXAS appear to have additive value in improving the detection of cognitively impaired patients. The MIS-t failed to contribute significantly to CDR-SOB, independent of the other measures. CONCLUSION: The AQ may have utility as a culture-fair telephone screening for MCI. The AQ was able to modestly distinguish MCI from NCs. The TEXAS adds variance to a model of dementia severity independent of the AQ, suggesting that the latter may weakly assess that cognitive domain (executive control function). On the other hand, the AQ attenuates the MIS-t effect. This suggests a prominent AQ bias in favor of detecting memory impairment. Additional studies are required to determine if the AQ can distinguish between amnestic and dysexecutive MCI subtypes, or between MCI and Alzheimer's disease in Hispanics.

Towards an aging-specific cognitive phenotype: the freedom house study.

UNLABELLED: BACKGROUND/STUDY CONTEXT: The authors have previously reported latent growth curve (LGC) models of 3-year change in multiple cognitive measures among successfully aging volunteers. In this analysis, the authors apply growth mixture modeling (GMM) to demonstrate homogeneous subsets among them with discriminable trajectories. Only one trajectory class can be interpreted as the effect of Aging Proper. The goal of the study was to describe an aging-specific cognitive phenotype (ASCP). METHODS: Five hundred forty-seven noninstitutionalized septuagenarian and octogenarian volunteers, residing in a comprehensive care retirement community, were assessed longitudinally on a comprehensive battery of brief psychometric measures. RESULTS: All variables held more than one latent class. Members of an a priori defined "Aging Proper" class were highly concordant across measures, and allowed the aging-specific cognitive phenotype (ASCP) to be examined. The ASCP was characterized by simultaneous decline in visuospatial function, coupled with improving verbal fluency. The ASCP was not associated with decline in memory task performance. CONCLUSIONS: Previously reported age-related declines in memory are more likely to represent the effects of comorbid disease and not aging per se. The ASCP is more consistent with earlier "Right Hemisphere" models of aging and could provide clues to the mechanisms underlying true aging-related cognitive changes.

INFLAMMATION's cognitive impact revealed by a novel "Line of Identity" approach.

IMPORTANCE: Dementia is an "overdetermined" syndrome. Few individuals are demented by any single biomarker, while several may independently explain small fractions of dementia severity. It may be advantageous to identify individuals afflicted by a specific biomarker to guide individualized treatment. OBJECTIVE: We aim to validate a psychometric classifier to identify persons adversely impacted by inflammation and replicate it in a second cohort. DESIGN: Secondary analyses of data collected by the Texas Alzheimer's Research and Care Consortium (TARCC) (N = 3497) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 1737). SETTING: Two large, well-characterized multi-center convenience samples. PARTICIPANTS: Volunteers with normal cognition (NC), Mild Cognitive Impairment (MCI) or clinical "Alzheimer's Disease (AD)". EXPOSURE: Participants were assigned to "Afflicted" or "Resilient" classes on the basis of a psychometric classifier derived by confirmatory factor analysis. MAIN OUTCOME(S) AND MEASURE(S): The groups were contrasted on multiple assessments and biomarkers. The groups were also contrasted regarding 4-year prospective conversions to "AD" from non-demented baseline diagnoses (controls and MCI). The Afflicted groups were predicted to have adverse levels of inflammation-related blood-based biomarkers, greater dementia severity and greater risk of prospective conversion. RESULTS: In ADNI /plasma, 47.1% of subjects were assigned to the Afflicted class. 44.6% of TARCC's subjects were afflicted, 49.5% of non-Hispanic Whites (NHW) and 37.2% of Mexican Americans (MA). There was greater dementia severity in the Afflicted class [by ANOVA: ADNI /F(1) = 686.99, p <0.001; TARCC /F(1) = 1544.01, p <0.001]. "INFLAMMATION" factor composite scores were significantly higher (adverse) in Afflicted subjects [by ANOVA in ADNI /plasma F(1) = 1642.64, p <0.001 and in TARCC /serum F(1) = 3059.96, p <0.001]. Afflicted cases were more likely to convert to AD in the next four years [by Cox's F, ADNI /plasma: F (252, 268) = 3.74 p < 0.001; TARCC /serum: F (160, 134) = 3.03, p < 0.001 (in TARCC's entire sample), F (110, 90) = 4.92, p <0.001 in NHW, and F(50, 44) = 2.13, p = 0.006 in MA]. The proportions converting were similar among afflicted NHW in both cohorts /biofluids but MA exhibited a lower risk (7% in TARCC /serum at 48 months). CONCLUSIONS AND RELEVANCE: Our inflammation-specific psychometric classifier selects individuals with pre-specified biomarker profiles and predicts conversion to "AD" across cohorts, biofluids, and ethnicities. This algorithm might be applied to any dementia-related biomarker making the psychometric estimation of individual biomarker effects feasible without biomarker assessment. Our approach also distinguishes individuals resilient to individual biomarker effects allowing for more accurate prediction and precision intervention.

Toward a cross-cultural understanding of intraindividual variability metrics.

OBJECTIVE: Compare the construct validity and predictive utility of cognitive intraindividual variability (IIV) in a sample of community-dwelling Hispanic and non-Hispanic white (NHW) older adults. METHODS: The present study included annual data from 651 older adult control participants (Hispanic = 293; NHW = 358) enrolled in the Texas Alzheimer's Research and Care Consortium for at least 5 years. Mean composite z-scores were calculated for attention, language, memory, and executive domains. IIV was calculated as was the standard deviation both within (IIV-Within) and between (IIV-Between) these domains. RESULTS: At baseline, NHW individuals obtained significantly higher mean scores in each domain than their Hispanic counterparts. They also showed significantly greater variability within and between domains, except for IIV-Within the language domain which was significantly larger in the Hispanic group. IIV-Between domains was driven primarily by IIV-Within the executive function domain in the NHW cohort and by IIV-Within the language domain in the Hispanic cohort. In both groups, the addition of IIV-Within and IIV-Between cognitive domains at baseline significantly improved prediction of global cognitive status after 5 years above and beyond demographic characteristics, genetic and cardiovascular risk. However, IIV-Between domains was the strongest predictor in the NHW group, while IIV-Within the attention domain was the strongest predictor in the Hispanic group. CONCLUSIONS: Findings suggest that, while IIV-Between domains is a promising adjunctive method for predicting future cognitive decline, its construct validity and predictive utility varies based on ethnic group.

Alzheimer's disease pathology does not mediate the association between depressive symptoms and subsequent cognitive decline.

BACKGROUND: Depressive symptoms in nondemented individuals appear to hasten the progression from mild cognitive impairment to clinical Alzheimer's disease (AD) and double the risk of incident AD. However, the mechanism(s) by which depression might affect this risk has not been well established. The purpose of this analysis was to test the hypothesis that AD pathology mediates depression's apparent effect on the risk of dementia conversion using longitudinally collected psychometric testing and autopsy data from the Honolulu-Asia Aging Study. METHODS: Latent factor variables representing AD, cortical Lewy body (CLB), and ischemic neuropathology were tested as potential mediators of the association between the Center for Epidemiological Studies depression scale (CES-D) score and the 10-year prospective rate of cognitive decline, adjusted for baseline cognition, age, education, total number of medications, and brain weight at autopsy. RESULTS: CES-D scores, neurofibrillary tangle counts, CLB counts, and ischemic lesions each made significant independent contributions to cognitive decline. However, CES-D scores were not significantly associated with any pathological variable; thus the pathological variables were not mediators of the effect of CES-D scores on cognitive decline. CONCLUSIONS: Subsyndromal depressive symptoms are significantly associated with subsequent cognitive decline. Although the effect is relatively modest, it is stronger than that of amyloid-related neuropathologies and independent of that of neurofibrillary tangles, cortical Lewy bodies, and ischemic lesions. Our results argue against the role of AD-related neuropathology as a mediator of depression's effect on cognitive decline, but cannot rule out a significant mediation effect in a subset of cases, perhaps with more severe baseline depressive symptoms.

Risk factors for mild cognitive impairment among Mexican Americans.

BACKGROUND: Although a great deal of literature has focused on risk factors for mild cognitive impairment (MCI), little published work examines risk for MCI among Mexican Americans. METHODS: Data from 1628 participants (non-Hispanic n = 1002; Mexican American n = 626) were analyzed from two ongoing studies of cognitive aging and Alzheimer's disease, Project FRONTIER (Facing Rural Obstacles to health Now Through Intervention, Education & Research) and TARCC (Texas Alzheimer's Research & Care Consortium). RESULTS: When looking at the full cohorts (non-Hispanic and Mexican American), age, education, Apolipoprotein E (APOE) ε4 status and gender were consistently related to MCI diagnosis across the two cohorts. However, when split by ethnicity, advancing age was the only significant risk factor for MCI among Mexican Americans across both cohorts. CONCLUSIONS: The current data suggest that many of the previously established risk factors for MCI among non-Hispanic cohorts may not be predictive of MCI among Mexican Americans and point to the need for additional work aimed at understanding factors related to cognitive aging among this underserved segment of the population.

Neuropsychological correlates of performance based functional status in elder adult protective services referrals for capacity assessments.

We have previously described high rates of executive function impairment in clients referred by Adult Protective Services (APS) to geriatric psychiatry for decision-making capacity assessments. The purpose of this study was to determine the independent relationship between neuropsychological screening instruments, particularly instruments sensitive to executive function, and performance-based functional tasks in elder referrals. Our retrospective medical review (n = 75/157 referrals completed all neuropsychological and functional assessments) revealed that only the Executive Interview (EXIT25) contributed independent variance to money management performance (R(2) = 0.29, p < 0.001), telephone use ability (R(2) = 0.39, p < 0.001), and summed performance (R(2) = 0.45, p < 0.001). Executive instruments may specifically inform decision-making capacity assessments.

Multiple Adipokines Predict Dementia Severity as Measured by δ: Replication Across Biofluids and Cohorts.

BACKGROUND: We have explored dementia's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. Among them are adipokines, i.e., proteins secreted by adipose tissue some of which have been associated with cognitive impairment. OBJECTIVE: To associate adipokines with dementia severity and replicate their association across cohorts and biofluids (serum /plasma). METHODS: We used eight rationally chosen blood-based protein biomarkers as indicators of a latent variable, i.e., "Adipokines". We then associated that construct with dementia severity as measured by the latent dementia-specific phenotype "δ" in structural equation models (SEM). Significant factor loadings and Adipokines' association with δ were replicated across biofluids in the Alzheimer's Disease Neuroimaging Initiative (ADNI). RESULTS: Eight adipokine proteins loaded significantly on the Adipokines construct. Adipokines measured in plasma (ADNI) or serum (TARCC) explained 24 and 70% of δ's variance, respectively. An Adipokine composite score, derived from the latent variables, rose significantly across clinical diagnoses and achieved high areas under the receiver operating characteristic curve (ROC/AUC) for discrimination of Alzheimer's disease from normal controls (NC) or cases of mild cognitive impairment (MCI) and between NC and MCI. CONCLUSION: These results again suggest that SEM can be used to create latent biomarker classifiers that replicate across samples and biofluids, and that a substantial fraction of dementia's variance is attributable to peripheral blood-based protein levels via the patterns codified in those latent constructs.

The effects of CNS atrophy and ICVD on tests of executive function and functional status are mediated by intelligence.

Background: Impairments in executive function (EF) are often attributed to ischemic cerebrovascular disease (ICVD) and frontal circuit pathology. However, EF can be distinguished from general intelligence and the latter is likely to manifest in "executive" measures. We aimed to distinguish the effects of imaging biomarkers on these constructs. Methods: We tested neuroimaging biomarkers as independent predictors of observed 12 month-prospective cognitive performance by a Multiple Indicators Multiple Causes (MIMIC) model in the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N ≅ 1750). Results: ICVD was associated with ''Organization" (ORG) and "Planning" (PLAN) domain scores from the test of Every Day Cognition. Left anterior cingulate (LAC) atrophy was independently associated with Trail-Making part B and Animal Naming. The MIMIC model had excellent fit and tests additional latent variables i.e., EF and dEF (a latent δ homolog derived from Spearman's general intelligence factor, g). Only dEF was associated with instrumental activities of daily living (IADL). ICVD and LAC were both associated with observed executive measures through dEF. ICVD was independently associated with those same measures through EF. Conclusions: Observed EF is independently determined by multiple factors. The effects of EF-associated MRI biomarkers can be related to disability and dementia only via their effects on g. Because g /δ are unlikely to be located within the frontal lobes, the dementia-specific variance in executive measures may have little to do with either frontal structure or function. Conversely, domain-specific variance in EF may have little to do with either IADL-impairment or dementia.

Cognitive intraindividual variability as a potential biomarker for early detection of cognitive and functional decline.

OBJECTIVE: Intraindividual variability (IIV) in cognitive performance has been associated with cognitive decline and reductions in white matter integrity, but the predictive utility of IIV-between versus IIV-within domains is unknown. The present study aimed to determine if IIV-within a "frontal-subcortical" domain may be a more robust predictor of changes in general cognitive status and functional independence over time than IIV-between cognitive domains. METHOD: Mixed linear modeling was used to analyze the relationship between cognitive IIV and cognitive and functional status in 651 controls, 211 people with mild cognitive impairment, and 218 people with Alzheimer's disease over a 5-year period. RESULTS: Both IIV-between and IIV-within a frontal-subcortical domain improved prediction of cognitive and functional declines beyond demographic characteristics, genetic risk, and vascular integrity. IIV-between showed the greatest effect over time and was driven primarily by increases in IIV-within. CONCLUSIONS: Cognitive IIV, especially between cognitive domains, may be useful for identifying individuals at risk for cognitive and functional decline. Findings may facilitate investigations into mechanisms underlying declines in global cerebral integrity and aid clinical trials aimed at early detection and treatment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Getting Past "g": testing a new model of dementing processes in persons without dementia.

The cognitive correlates of functional status are essential to dementia case-finding. The authors have used structural-equation models to explicitly distinguish dementia-relevant variance in cognitive task performance (i.e., δ) from the variance that is unrelated to a dementing process (i.e., g'). Together, g' and δ comprise Spearman's "g." Although δ represents only a small fraction of the total variance in cognitive task performance, it is more strongly associated with dementia severity than is g'. In this analysis, the authors test whether δ can predict future cognitive decline in persons clinically without dementia at baseline. These results have implications for the clinical assessment of dementia and suggest that functional status should assume a more important role.

Depressive symptoms predict longitudinal change in executive control but not memory.

OBJECTIVE: Depression in non-demented persons has been identified as a possible risk factor for incident Alzheimer's disease (AD). METHODS: Latent Growth Curve models were developed of baseline depressive symptoms as a predictor of longitudinal changes in cognition. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS). Memory was assessed by the California Verbal Learning Task (CVLT). Executive control function (ECF) was assessed by the Executive Interview (EXIT25) and Trail-Making Test Part B (Trails-B). Five hundred forty-seven non-institutionalized older retirees living in a single comprehensive care retirement community participated. RESULTS: Depressive symptoms were significantly associated only with the 3-year rate of decline in psychomotor speed, as measured by Trails A, and ECF, as measured by the EXIT25. Both associations withstood adjustment for age, gender, education, and baseline level of care. CONCLUSIONS: Depressive symptoms are associated with longitudinal decline in cognition. However, this association selectively involves executive control, not memory, and possibly only a subset of 'executive' functions. Although depressive symptoms may hasten conversion from mild cognitive impairment (MCI) to dementia, depression-related conversion is not likely to be mediated by evolution of the AD pathological process.