BACKGROUND/OBJECTIVES: Behavioral problems in individuals with Alzheimer's disease (AD) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI). DESIGN: Longitudinal observational cohort study. SETTING: Academic medical center. PARTICIPANTS: Members of an apolipoprotein E (APOE) ɛ4 genetically enriched cohort of Maricopa County residents who were neuropsychiatrically healthy at entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had the Neuroticism, Extraversion, and Openness Personality Inventory-Revised (NEO-PI-R) before and during the MCI transition epoch were compared with 252 nontransitioners also with serial NEO-PI-R administrations. INTERVENTION: Longitudinal administration of the NEO-PI-R and neuropsychological test battery. MEASUREMENTS: Change in NEO-PI-R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from entry to the epoch of MCI diagnosis or an equivalent follow-up duration in nontransitioners. RESULTS: NEO-PI-R neuroticism T-scores increased significantly more in MCI transitioners than in nontransitioners (mean 2.9, 95% confidence interval (CI) = 0.9-4.9 vs 0, 95% CI = À0.7-0.7, P = .02), and openness decreased more in MCI transitioners than in nontransitioners (À4.8, 95% CI = À7.3 to À2.4 vs À1.0, 95% CI = À1.6 to

BackgroundAlthough there are studies investigating the pathologic origins of mild cognitive impairment (MCI), they have revolved around comparisons to normal elderly individuals or those with Alzheimer’s disease (AD) or other dementias. There are few studies directly comparing the comprehensive neuropathology of amnestic (aMCI) and nonamnestic (naMCI) MCI.MethodsThe database of the Brain and Body Donation Program (www.brainandbodydonationprogram.org), a longitudinal clinicopathological study of normal aging and neurodegenerative disorders, was queried for subjects who were carrying a diagnosis of aMCI or naMCI at the time of autopsy. Neuropathological lesions, including neuritic plaques, neurofibrillary tangles (NFTs), Lewy bodies (LBs), infarcts, cerebral white matter rarefaction (CWMR), cerebral amyloid angiopathy (CAA), and concurrent major clinicopathological diagnoses, including Parkinson’s disease (PD) were analyzed.ResultsThirty four subjects with aMCI and 15 naMCI met study criteria. Subjects with aMCI were older at death (88 vs. 83 years of age, p = 0.03). Individuals with naMCI had higher densities of LBs within the temporal lobe (p = 0.04) while subjects with aMCI had a propensity for increased NFTs in parietal and temporal lobes (p values = 0.07). After adjusting for age at death, the only significant difference was greater densities of temporal lobe NFTs within the aMCI group. Other regional pathology scores for plaques, NFTs, and LBs were similar between groups. Subjects met clinico-pathological criteria for co-existent PD in 24 % aMCI and 47 % naMCI while neuropathological criteria for AD were met in equal percentages of aMCI and of naMCI cases (53 %); these proportional differences were not significant (p values > 0.35). Furthermore, regardless of amnestic status, there was a greater presence of CAA (71 % of MCI with executive dysfunction vs. 39 % without p = 0.03) and a greater presence of CWMR (81 % of MCI with executive dysfunction and 54 % without p = 0.046) in MCI cases with executive dysfunction.ConclusionsNo single pathologic entity strongly dichotomized MCI groups, perhaps due to the pathologic heterogeneity found within both entities. However, these data suggest the possibility for naMCI to have a propensity for increased LBs and aMCI for increased NFTs in select anatomic regions.

Neuroticism and Conscientiousness were associated with changes in longitudinal performances on tests sensitive to memory and executive skills. APOE interactions were less consistent. Our findings are consistent with previous studies that have suggested that personality factors, particularly Neuroticism and Conscientiousness are associated with cognitive aging patterns. (JINS, 2016, 22, 765-776).

Given the limited success of medication in reversing the effects of Alzheimer's and other dementias, a lot of the neuroscience research has been focused on early detection, in order to slow the progress of the disease through different interventions. We propose a Natural Language Processing approach applied to descriptive writing to attempt to discriminate decline due to normal aging from decline due to predementia conditions. Within the context of a longitudinal study on Alzheimer's disease, we created a unique corpus of 201 descriptions of a control image written by subjects of the study. Our classifier, computing linguistic features, was able to discriminate normal from cognitively impaired patients to an accuracy of 86.1% using lexical and semantic irregularities found in their writing. This is a promising result towards elucidating the existence of a general pattern in linguistic deterioration caused by dementia that might be detectable from a subject's written descriptive language.

Background:Age-related declines in memory have been well-documented. However, some individuals reach their 8 th -10 th decade while maintaining strong memory performance. We were interested in which demographic and biomarker variables distinguished individuals aged 75+ who score in the top 20 th percentile for memory (Optimal Agers) from their typically scoring peers (Typical Agers). Methods: A total of 125 clinically healthy older adults (CDR¼0; MMSE: 28.7861.07) aged 75-90 from the Harvard Aging Brain Study underwent annual memory testing and neuroimaging (MRI and PET amyloid) at baseline and 3-year follow-up. A memory composite score was derived from standardized and challenging tests including the 6-Trial Selective Reminding Test, Memory Capacity Test, and Face-Name Associative Memory Exam. Participants were grouped into Optimal Agers (n¼25) vs. Typical Agers (n¼100) based on their memory composite scores. Follow-up data available on 20 of the 25 Optimal Agers revealed that 12 individuals maintained their optimal status (Optimal Maintainers) while 8 declined compared to their initial performance (Optimal Non-Maintainers). T-tests, Mann Whitney U tests, and c 2 tests were used to compare groups on b-amyloid accumulation, and ICV-adjusted hippocampal volume. Results: There were no group differences in demographics. At baseline, Optimal Agers tended to have larger hippocampal volumes (ICV adjusted Vol¼7319.82) compared with Typical Agers (ICV adjusted Vol¼ 6917.12) (t(123)¼-2.79 p¼0.01). At 3-year follow-up, those who maintained their optimal status had lower amyloid levels at baseline (mean DVR¼1.18) in contrast to Non-Maintainers (mean DVR¼ 1.46) (U¼20, p¼0.031). Optimal Maintainers also had lower rates of amyloid accumulation (0.02 DVR/year) compared to Non-Maintainers (0.05 DVR/ year)) (t(16)¼2.45, p¼0.026). Conclusions: Optimal memory performance in those 75+ years of age was associated with larger hippocampi at baseline. Those who maintained optimal performance over 3 years had lower amyloid levels and lower rates of amyloid accumulation but no difference in hippocampal volumes. Understanding factors associated with brain resilience may help better predict an individual's dementia trajectory.