Association of CSF Biomarkers With Hippocampal-Dependent Memory in Preclinical Alzheimer Disease.

OBJECTIVE: To determine whether memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer disease (AD) biomarkers, we examined associations between performance in 3 memory tasks and CSF ß-amyloid (Aß)42/Aß40 and phosopho-tau181 (p-tau181) in cognitively unimpaired older adults (CU). METHODS: CU enrolled in the Stanford Aging and Memory Study (n = 153; age 68.78 ± 5.81 years; 94 female) completed a lumbar puncture and memory assessments. CSF Aß42, Aß40, and p-tau181 were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied "target" objects, novel "foil" objects, and perceptually similar "lure" objects. Analyses examined cross-sectional relationships among memory performance, age, and CSF measures, controlling for sex and education. RESULTS: Age and lower Aß42/Aß40 were independently associated with elevated p-tau181. Age, Aß42/Aß40, and p-tau181 were each associated with (1) poorer associative memory and (2) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aß42/Aß40 on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF Aß42 was not significantly associated with p-tau181 or memory. CONCLUSIONS: Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying CU with preclinical AD pathology.

Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases.

PURPOSE: In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD). METHODS: Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aß+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum. RESULTS: SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aß+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient. CONCLUSION: Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults.

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

Altered Cortical Brain Structure and Increased Risk for Disease Seen Decades After Perinatal Exposure to Maternal Smoking: A Study of 9000 Adults in the UK Biobank.

Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44-80) who were exposed (n = 2510) or unexposed (n = 6079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volumes. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE-) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+ adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n = 109, unexposed, n = 315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

Oral health and medical conditions among Amish children.

BACKGROUND: The Amish are a growing population who live a traditional, rural way of life, which makes them less accepting of modernism. Most Amish live in poverty and are detached from modern health care. In addition, the recent change of their lifestyle has been reported, such as consuming a nontraditional diet and the usage of electronic devices. As a result, their lifestyle change may have impacted their oral health. However, since only a single report about oral health among Amish children has been published approximately three decades ago it has not yet been updated. This study describes oral health among Amish children and their medical conditions during visits to a mobile dental unit (MDU). MATERIAL AND METHODS: The dental records of all patients (N=216) who visited a mobile dental unit were reviewed, which covers 1 year from May 20, 2011, the first date of service. The following factors were taken into consideration during the review process: parental perceptions of their children's oral health care, dental care experiences, and general health information. RESULTS: Fifty-four (27.8%) children, ages 3 to 17, have never received dental treatment before visiting the MDU; the average number of untreated decayed teeth was 6.8. In spite of this, most parents rated their children's oral health as good or very good (87.7%). The high cost and long distance travel associated with routine, professional dental care makes it difficult for children to maintain good oral hygiene. Our analysis revealed that bleeding disorders were more prevalent among this gene pool compared to the nation at large; however, asthma was less common. CONCLUSIONS: There are oral and general health disparities among Amish children. There is a lack of awareness among Amish parents with regard to their children's oral health. Key words:Amish, child, dental caries, mobile health units.

Retrosplenial Cortical Neurons Encode Navigational Cues, Trajectories and Reward Locations During Goal Directed Navigation.

The retrosplenial cortex (RSC) plays an important role in memory and spatial navigation. It shares functional similarities with the hippocampus, including the presence of place fields and lesion-induced impairments in spatial navigation, and the RSC is an important source of visual-spatial input to the hippocampus. Recently, the RSC has been the target of intense scrutiny among investigators of human memory and navigation. fMRI and lesion data suggest an RSC role in the ability to use landmarks to navigate to goal locations. However, no direct neurophysiological evidence of encoding navigational cues has been reported so the specific RSC contribution to spatial cognition has been uncertain. To examine this, we trained rats on a T-maze task in which the reward location was explicitly cued by a flashing light and we recorded RSC neurons as the rats learned. We found that RSC neurons rapidly encoded the light cue. Additionally, RSC neurons encoded the reward and its location, and they showed distinct firing patterns along the left and right trajectories to the goal. These responses may provide key information for goal-directed navigation, and the loss of these signals may underlie navigational impairments in subjects with RSC damage.

The mental health country profile: background, design and use of a systematic method of appraisal.

This article describes the construction and use of a systematic structured method of mental health country situation appraisal, in order to help meet the need for conceptual tools to assist planners and policy makers develop and audit policy and implementation strategies. The tool encompasses the key domains of context, needs, resources, provisions and outcomes, and provides a framework for synthesizing key qualitative and quantitative information, flagging up gaps in knowledge, and for reviewing existing policies. It serves as an enabling tool to alert and inform policy makers, professionals and other key stakeholders about important issues which need to be considered in mental health policy development. It provides detailed country specific information in a systematic format, to facilitate global sharing of experiences of mental health reform and strategies between policy makers and other stakeholders. Lastly, it is designed to be a capacity building tool for local stakeholders to enhance situation appraisal, and multisectorial policy development and implementation.