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Background: Neuropsychiatric symptoms are uncommon at Alzheimer's Disease (AD) dementia diagnosis but are exhibited by nearly everyone during the course of dementia. Depressive symptoms are common in AD dementia. We sought to determine correlations between memory, executive functioning, language, neuropsychiatric symptoms, and depressive symptoms at AD dementia diagnosis, and to characterize neuropsychiatric and depressive symptoms across groups defined by substantial relative cognitive impairments, using data from the National Alzheimer's Coordinating Center (NACC). Method: Using confirmatory factor analysis, we derived composite Neuropsychiatric Inventory Questionnaire (NPI‐Q) and Geriatric Depression Scale (excluding the memory question) scores. We defined a reference category of people with AD dementia whose memory, executive functioning, and language scores were similar to each other. Other groups were defined based on relative differences in cognitive domain scores. We used multinomial logistic regression to test if neuropsychiatric and depressive symptoms differed across groups. Result: Our sample included the diagnosis visit for 7,747 people with AD dementia and CDR = 1 (Table 1). Correlations between cognitive domains ranged from +0.29 to +0.50. Correlations between cognitive domains and NPI‐Q composite scores ranged from ‐0.02 to +0.04 and with depressive symptoms from ‐0.09 to +0.14. The correlation between depressive symptoms and the NPI‐Q composite was +0.17. We did not find a difference in NPI‐Q composite scores across groups, but depressive symptom score differed across groups (p<0.0001), with higher scores in people with relatively greater executive functioning impairments and lower scores in people with relatively greater memory impairments, compared to people with similar domain scores (Figure 1, Table 2). Conclusion: Composite scores for depressive and neuropsychiatric symptoms facilitate well‐powered investigations of relationships with these clinically salient factors. Neuropsychiatric symptoms had trivial correlations with cognitive domain scores at AD dementia diagnosis, and did not differ across groups defined by substantial relative cognitive impairments. Depressive symptoms were weakly correlated with cognitive domain scores, and differed across groups defined by substantial relative cognitive impairments. More research is warranted to further characterize depression and neuropsychiatric symptoms over the course of AD dementia. [ABSTRACT FROM AUTHOR]

Background: The relationship between Alzheimer's disease (AD) pathology and the associated clinical syndrome a patient presents with remains indeterminate. Cognitively‐defined subgroups of AD have revealed distinctions based on relative cognitive impairments, including AD‐Language, where challenges in language are substantial, and AD‐No Domain, where no relative asymmetries across cognitive domains occur. Pathological features of AD have been associated as the primary neuropathology of the logopenic variant of primary progressive aphasia (lvPPA). Hallmark clinical features of lvPPA include relatively spared comprehension in the face of decline in naming and repetition abilities. This work aimed to test the hypothesis that the lvPPA language profile was overrepresented in AD‐Language when compared to AD‐No Domain. Method: Measures of verbal comprehension, confrontation naming, and phrase‐level repetition were obtained from all participants from the Religious Orders Study (ROS), the RUSH Memory and Aging Project (MAP) and the Minority Aging Research Study (MARS) using confirmatory factor analyses. We subsetted the data to include participants belonging to the AD‐Language and AD‐No Domain groups at their initial AD diagnosis visit. We compared patterns of language profiles based on strengths and weaknesses in comprehension, naming, and repetition. Pearson's Chi‐squared tests with Yates continuity correction was used to test if the language patterns were statistically different between the two AD subgroups. Results: We analyzed language performance in 642 participants across AD‐Language (31.8%) and AD‐No Domain (68.2%) groups (Table 1). Thresholds were based on AD‐No Domain and set as the median for each subdomain (comprehension = ‐.101, naming = ‐.957, repetition =.233) to establish whether a score represented a relative strength or weakness in the language profile. Eight patterns of language profiles based on strengths and weaknesses in comprehension, naming, and repetition were formed (Figure 1). The distribution of language patterns differed significantly between AD‐Language and AD‐No Domain (χ2 = 97.6, p <.001). Furthermore, the lvPPA pattern was found more frequently in AD‐Language (χ2 = 28.1, p <.001). Conclusion: Heterogeneity within the AD‐Language spectrum includes a significant proportion that is consistent with the language profile of lvPPA. Relative performance in domains of verbal comprehension, confrontation naming, and phrase‐level repetition varied by AD subgroup. [ABSTRACT FROM AUTHOR]

Background: Aging is often characterized by progressive cognitive decline in memory and executive function. Yet, some adults aged 80 years or older, are "Super‐Agers" that exhibit cognitive performance akin to younger adults. It is unknown if there are adults in mid‐life with similar superior cognitive performance ("positive‐aging") versus cognitive decline over time, and if there are blood biomarkers that can distinguish between these groups. Method: Among 1303 participants in UK Biobank, latent growth curve models classified participants into different cognitive groups based on longitudinal Fluid Intelligence (FI) scores over 7‐9 years. Random Forest (RF) classification was then used to predict cognitive trajectory types using longitudinal predictors including demographic, vascular, bioenergetic, and immune factors. Feature ranking importance and performance metrics of the model were reported. Result: Despite model complexity, we achieved a precision of 77% when determining who would be in the "positive‐aging" group. Among the top fifteen features, an equal number were related to either vascular health or cellular bioenergetics but not demographics like age, sex, or socioeconomic status (see figure). Conclusion: Our results suggest that optimal cognitive aging may not be driven by age per se, but biological factors that may be amenable to lifestyle or pharmacological changes. [ABSTRACT FROM AUTHOR]

Background: To determine if 3‐year changes in serum insulin resistance (IR) were related to changes in brain volume and glucose uptake, cognition, and CSF biomarkers in cognitively unimpaired and impaired older adults. Method: Alzheimer's Disease Neuroimaging Initiative data was downloaded for 275 aged adults (55‐89 years). Participants had longitudinal T1‐ and T2‐weighted volume scans, fluorodeoxyglucose (FDG) scans, CSF β‐amyloid (Aβ) and tau species, and cognitive performance over baseline and months 6, 12, 18, 24, and 36. Growth curve modeling in R regressed IR against these outcomes, by itself and with clinical diagnosis as a moderator. Cognitively unimpaired (CU) adults were used as a reference group to determine potential effects in pathological aging. Result: In AD and/or Mild Cognitive Impairment progressors to AD (MCI‐P), higher IR over time was related to progressive atrophy in medial temporal frontoinsular areas. Similarly, decline was seen in global cognition and both memory and executive function. HOMA1‐IR associations were partially mediated by p‐tau‐181. Among clinical diagnosis groups, higher IR was significantly related to amyloid, p‐tau‐181, and total tau 181 among AD patients but not MCI or unimpaired groups. Conclusion: These findings suggest that in older adults who develop AD or had AD at baseline, higher IR over time is related to brain atrophy and consequent cognitive decline, perhaps as a function of amyloid or tau deposition. [ABSTRACT FROM AUTHOR]

Background: 58‐79% of late‐onset Alzheimer's disease (AD) is due to genetic heritability. The epsilon 4 (ε4) variant of Apolipoprotein E (APOE) is the strongest genetic risk factor for AD, yet only accounts for 20% of AD heritability. In addition, the APOE ε2 or ε3 variants appear to have either a protective or neutral effect on AD risk respectively. Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is next to APOE and may modulate different APOE variant effects, such as with the Single Nucleotide Polymorphism (SNP) at rs2075650. Thus, we explored main and interaction effects of TOMM40 and APOE on longitudinal measures of executive function and memory. Method: 10,347 adults (40‐70y) in the UK Biobank were genotyped for APOE and TOMM40 '650. Executive function and memory were tested at baseline and twice over a period of 6‐10 years. Main effects within APOE haplotypes and TOMM40 SNP genotypes (A,G) were analyzed, as well as interactions between these genetic markers. Result: Having the TOMM40 '650 G risk variant was related to better baseline cognitive scores regardless of APOE haplotype (ps <.05), but a greater decline over time in APOE4 carriers (ps <.05) The effects of the APOE haplotype were strongly modulated by sex. Men vs. women had less protective or more detrimental effects based on APOE2 or APOE4 haplotype respectively. Conclusion: The data suggests that TOMM40 modulates APOE, regardless of its haplotype. Future studies should stratify APOE by haplotype to re‐test our findings. In addition, more research needs to be done on the effect of having what we term a "mixed" APOE haplotype (carrying a copy of both the protective and risk gene variants). [ABSTRACT FROM AUTHOR]