Diversity, equity, and inclusivity in observational ambulatory assessment: Recommendations from two decades of Electronically Activated Recorder (EAR) research.

Ambient audio sampling methods such as the Electronically Activated Recorder (EAR) have become increasingly prominent in clinical and social sciences research. These methods record snippets of naturalistically assessed audio from participants' daily lives, enabling novel observational research about the daily social interactions, identities, environments, behaviors, and speech of populations of interest. In practice, these scientific opportunities are equaled by methodological challenges: researchers' own cultural backgrounds and identities can easily and unknowingly permeate the collection, coding, analysis, and interpretation of social data from daily life. Ambient audio sampling poses unique and significant challenges to cultural humility, diversity, equity, and inclusivity (DEI) in scientific research that require systematized attention. Motivated by this observation, an international consortium of 21 researchers who have used ambient audio sampling methodologies created a workgroup with the aim of improving upon existing published guidelines. We pooled formally and informally documented challenges pertaining to DEI in ambient audio sampling from our collective experience on 40+ studies (most of which used the EAR app) in clinical and healthy populations ranging from children to older adults. This article presents our resultant recommendations and argues for the incorporation of community-engaged research methods in observational ambulatory assessment designs looking forward. We provide concrete recommendations across each stage typical of an ambient audio sampling study (recruiting and enrolling participants, developing coding systems, training coders, handling multi-linguistic participants, data analysis and interpretation, and dissemination of results) as well as guiding questions that can be used to adapt these recommendations to project-specific constraints and needs.

The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort.

INTRODUCTION: Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early-onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. METHODS: We analyzed MRI scans to define the sporadic EOAD-signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early-onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment. RESULTS: The EOAD-signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD-signature atrophy was associated with the severity of cognitive impairment. DISCUSSION: The EOAD-signature atrophy is a reliable and clinically valid biomarker of AD-related neurodegeneration that could be used in clinical trials for EOAD. HIGHLIGHTS: We developed an early-onset Alzheimer's disease (EOAD)-signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD-signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.

Loneliness and social isolation are not associated with executive functioning in a cross-sectional study of cognitively healthy older adults.

The literature on the relationship between social interaction and executive functions (EF) in older age is mixed, perhaps stemming from differences in EF measures and the conceptualization/measurement of social interaction. We investigated the relationship between social interaction and EF in 102 cognitively unimpaired older adults (ages 65-90). Participants received an EF battery to measure working memory, inhibition, shifting, and global EF. We measured loneliness subjectively through survey and social isolation objectively through naturalistic observation. Loneliness was not significantly related to any EF measure (p-values = .13-.65), nor was social isolation (p-values = .11-.69). Bayes factors indicated moderate to extremely strong evidence (BF01 = 8.70 to BF01 = 119.49) in support of no relationship.. Overall, these findings suggest that, among cognitively healthy older adults, there may not be a robust cross-sectional relationship between EF and subjective loneliness or objective social isolation.

Criterion Validation of Tau PET Staging Schemes in Relation to Cognitive Outcomes.

BACKGROUND: Utilization of NIA-AA Research Framework requires dichotomization of tau pathology. However, due to the novelty of tau-PET imaging, there is no consensus on methods to categorize scans into "positive" or "negative" (T+ or T-). In response, some tau topographical pathologic staging schemes have been developed. OBJECTIVE: The aim of the current study is to establish criterion validity to support these recently-developed staging schemes. METHODS: Tau-PET data from 465 participants from the Alzheimer's Disease Neuroimaging Initiative (aged 55 to 90) were classified as T+ or T- using decision rules for the Temporal-Occipital Classification (TOC), Simplified TOC (STOC), and Lobar Classification (LC) tau pathologic schemes of Schwarz, and Chen staging scheme. Subsequent dichotomization was analyzed in comparison to memory and learning slope performances, and diagnostic accuracy using actuarial diagnostic methods. RESULTS: Tau positivity was associated with worse cognitive performance across all staging schemes. Cognitive measures were nearly all categorized as having "fair" sensitivity at classifying tau status using TOC, STOC, and LC schemes. Results were comparable between Schwarz schemes, though ease of use and better data fit preferred the STOC and LC schemes. While some evidence was supportive for Chen's scheme, validity lagged behind others-likely due to elevated false positive rates. CONCLUSIONS: Tau-PET staging schemes appear to be valuable for Alzheimer's disease diagnosis, tracking, and screening for clinical trials. Their validation provides support as options for tau pathologic dichotomization, as necessary for use of NIA-AA Research Framework. Future research should consider other staging schemes and validation with other outcome benchmarks.

A simulative deep learning model of SNP interactions on chromosome 19 for predicting Alzheimer's disease risk and rates of disease progression.

BACKGROUND: Identifying genetic patterns that contribute to Alzheimer's disease (AD) is important not only for pre-symptomatic risk assessment but also for building personalized therapeutic strategies. METHODS: We implemented a novel simulative deep learning model to chromosome 19 genetic data from the Alzheimer's Disease Neuroimaging Initiative and the Imaging and Genetic Biomarkers of Alzheimer's Disease datasets. The model quantified the contribution of each single nucleotide polymorphism (SNP) and their epistatic impact on the likelihood of AD using the occlusion method. The top 35 AD-risk SNPs in chromosome 19 were identified, and their ability to predict the rate of AD progression was analyzed. RESULTS: Rs561311966 (APOC1) and rs2229918 (ERCC1/CD3EAP) were recognized as the most powerful factors influencing AD risk. The top 35 chromosome 19 AD-risk SNPs were significant predictors of AD progression. DISCUSSION: The model successfully estimated the contribution of AD-risk SNPs that account for AD progression at the individual level. This can help in building preventive precision medicine.

Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease.

INTRODUCTION: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD). METHODS: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden. RESULTS: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non-carriers also had greater gray matter atrophy than female ε4 carriers. DISCUSSION: The effects of sex and APOE ε4 must be considered when studying these populations. HIGHLIGHTS: Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE Îµ4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.

Barriers and facilitators to participating in Alzheimer's disease biomarker research in black and white older adults.

Introduction: The study examined Black and White prospective participants' views of barriers to and facilitators of participation in Alzheimer's disease (AD) biomarker research. Methods: In a mixed-methods study, 399 community-dwelling Black and White older adults (age ≥55) who had never participated in AD research completed a survey about their perceptions of AD biomarker research. Individuals from lower socioeconomic and education backgrounds and Black men were over-sampled to address perspectives of traditionally under-represented groups. A subset of participants (n = 29) completed qualitative interviews. Results: Most participants expressed interest in biomarker research (overall 69%). However, Black participants were comparatively more hesitant than White participants (28.9% vs 15.1%), were more concerned about study risks (28.9% vs 15.1%), and perceived multiple barriers to participating in brain scans. These results persisted even after adjusting for trust and perceived knowledge of AD. Information was a primary barrier (when absent) and incentive (when provided) for AD biomarker research participation. Black older adults desired more information about AD (eg, risk, prevention), general research processes, and specific biomarker procedures. They also desired return of results to make informed decisions about their health, research-sponsored community awareness events, and for researchers to mitigate the burden placed on participants in research (eg, transportation, basic needs). Conclusion: Our findings increase representativeness in the literature by focusing on individuals with no history of AD research experience and those from traditionally underrepresented groups in research. Results suggest that the research community needs to improve information sharing and raising awareness, increase their presence in the communities of underrepresented groups, reduce incidental costs, and provide valuable personal health information to participants to increase interest. Specific recommendations for improving recruitment are addressed. Future studies will assess the implementation of evidence-based, socioculturally sensitive recruitment strategies to increase enrollment of Black older adults into AD biomarker studies.HIGHLIGHTS: Individuals from under-represented groups are interested in Alzheimer's disease (AD) biomarker research.After adjusting for trust and AD knowledge, Black participants were still more hesitant.Information is a barrier (when absent) to and incentive (when given) for biomarker studies.Reducing burden (e.g., transportation) is essential for recruiting Black older adults.

Baseline neuropsychiatric symptoms and psychotropic medication use midway through data collection of the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort.

INTRODUCTION: We examined neuropsychiatric symptoms (NPS) and psychotropic medication use in a large sample of individuals with early-onset Alzheimer's disease (EOAD; onset 40-64 years) at the midway point of data collection for the Longitudinal Early-onset Alzheimer's Disease Study (LEADS). METHODS: Baseline NPS (Neuropsychiatric Inventory - Questionnaire; Geriatric Depression Scale) and psychotropic medication use from 282 participants enrolled in LEADS were compared across diagnostic groups - amyloid-positive EOAD (n = 212) and amyloid negative early-onset non-Alzheimer's disease (EOnonAD; n = 70). RESULTS: Affective behaviors were the most common NPS in EOAD at similar frequencies to EOnonAD. Tension and impulse control behaviors were more common in EOnonAD. A minority of participants were using psychotropic medications, and use was higher in EOnonAD. DISCUSSION: Overall NPS burden and psychotropic medication use were higher in EOnonAD than EOAD participants. Future research will investigate moderators and etiological drivers of NPS, and NPS differences in EOAD versus late-onset AD.

Profiling baseline performance on the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort near the midpoint of data collection.

OBJECTIVE: The Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer's disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point. METHODS: Data from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid-positive EOAD [n = 212], and amyloid-negative early-onset non-Alzheimer's disease [EOnonAD; n = 70]). RESULTS: Cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures. CONCLUSIONS: We present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant. HIGHLIGHTS: Findings represent the most comprehensive baseline characterization of sporadic early-onset Alzheimer's disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.

The paucity of morality in everyday talk.

Given its centrality in scholarly and popular discourse, morality should be expected to figure prominently in everyday talk. We test this expectation by examining the frequency of moral content in three contexts, using three methods: (a) Participants' subjective frequency estimates (N = 581); (b) Human content analysis of unobtrusively recorded in-person interactions (N = 542 participants; n = 50,961 observations); and (c) Computational content analysis of Facebook posts (N = 3822 participants; n = 111,886 observations). In their self-reports, participants estimated that 21.5% of their interactions touched on morality (Study 1), but objectively, only 4.7% of recorded conversational samples (Study 2) and 2.2% of Facebook posts (Study 3) contained moral content. Collectively, these findings suggest that morality may be far less prominent in everyday life than scholarly and popular discourse, and laypeople, presume.

APOE ε4 is associated with earlier symptom onset in LOAD but later symptom onset in EOAD.

BACKGROUND: We studied the effect of apolipoprotein E (APOE) ε4 status and sex on age of symptom onset (AO) in early- (EO) and late- (LO) onset Alzheimer's disease (AD). METHOD: A total of 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center (NACC) were included. We used analysis of variance to examine AO differences between sexes and APOE genotypes and the effect of APOE ε4, sex, and their interaction on AO in EOAD and LOAD, separately. RESULTS: APOE ε4 carriers in LOAD had younger AO and in EOAD had older AO. Female EOAD APOE ε4 carriers had older AO compared to non-carriers (P < 0.0001). There was no difference for males. Both male and female LOAD APOE ε4 carriers had younger AO relative to non-carriers (P < 0.0001). CONCLUSION: The observed earlier AO in EOAD APOE ε4 non-carriers relative to carriers, particularly in females, suggests the presence of additional AD risk variants.

APOE ε4 carrier status and sex differentiate rates of cognitive decline in early- and late-onset Alzheimer's disease.

BACKGROUND: We studied the effect of apolipoprotein E (APOE) ε4 status and sex on rates of cognitive decline in early- (EO) and late- (LO) onset Alzheimer's disease (AD). METHOD: We ran mixed-effects models with longitudinal cognitive measures as dependent variables, and sex, APOE ε4 carrier status, and interaction terms as predictor variables in 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center. RESULTS: APOE ε4 carriers showed accelerated cognitive decline relative to non-carriers in both EOAD and LOAD, although the patterns of specific cognitive domains that were affected differed. Female participants showed accelerated cognitive decline relative to male participants in EOAD only. The effect of APOE ε4 was greater in EOAD for executive functioning (p < 0.0001) and greater in LOAD for language (p < 0.0001). CONCLUSION: We found APOE ε4 effects on cognitive decline in both EOAD and LOAD and female sex in EOAD only. The specific patterns and magnitude of decline are distinct between the two disease variants. HIGHLIGHTS: Apolipoprotein E (APOE) ε4 carrier status and sex differentiate rates of cognitive decline in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD). APOE ε4 in EOAD accelerated decline in memory, executive, and processing speed domains. Female sex in EOAD accelerated decline in language, memory, and global cognition. The effect of APOE ε4 was stronger for language in LOAD and for executive function in EOAD. Sex effects on language and executive function decline differed between EOAD and LOAD.

Atypical Alzheimer Disease Variants.

PURPOSE OF REVIEW: This article discusses the clinical, neuroimaging, and biomarker profiles of sporadic atypical Alzheimer disease (AD) variants, including early-onset AD, posterior cortical atrophy, logopenic variant primary progressive aphasia, dysexecutive variant and behavioral variant AD, and corticobasal syndrome. RECENT FINDINGS: Significant advances are being made in the recognition and characterization of the syndromically diverse AD variants. These variants are identified by the predominant cognitive and clinical features: early-onset amnestic syndrome, aphasia, visuospatial impairments, dysexecutive and behavioral disturbance, or motor symptoms. Although understanding of regional susceptibility to disease remains in its infancy, visualizing amyloid and tau pathology in vivo and CSF examination of amyloid-ß and tau proteins are particularly useful in atypical AD, which can be otherwise prone to misdiagnosis. Large-scale research efforts, such as LEADS (the Longitudinal Early-Onset Alzheimer Disease Study), are currently ongoing and will continue to shed light on our understanding of these diverse presentations. SUMMARY: Understanding the clinical, neuroimaging, and biomarker profiles of the heterogeneous group of atypical AD syndromes improves diagnostic accuracy in patients who are at increased risk of misdiagnosis. Earlier accurate identification facilitates access to important interventions, social services and disability assistance, and crucial patient and family education.

Predicting Working Memory in Healthy Older Adults Using Real-Life Language and Social Context Information: A Machine Learning Approach.

BACKGROUND: Language use and social interactions have demonstrated a close relationship with cognitive measures. It is important to improve the understanding of language use and behavioral indicators from social context to study the early prediction of cognitive decline among healthy populations of older adults. OBJECTIVE: This study aimed at predicting an important cognitive ability, working memory, of 98 healthy older adults participating in a 4-day-long naturalistic observation study. We used linguistic measures, part-of-speech (POS) tags, and social context information extracted from 7450 real-life audio recordings of their everyday conversations. METHODS: The methods in this study comprise (1) the generation of linguistic measures, representing idea density, vocabulary richness, and grammatical complexity, as well as POS tags with natural language processing (NLP) from the transcripts of real-life conversations and (2) the training of machine learning models to predict working memory using linguistic measures, POS tags, and social context information. We measured working memory using (1) the Keep Track test, (2) the Consonant Updating test, and (3) a composite score based on the Keep Track and Consonant Updating tests. We trained machine learning models using random forest, extreme gradient boosting, and light gradient boosting machine algorithms, implementing repeated cross-validation with different numbers of folds and repeats and recursive feature elimination to avoid overfitting. RESULTS: For all three prediction routines, models comprising linguistic measures, POS tags, and social context information improved the baseline performance on the validation folds. The best model for the Keep Track prediction routine comprised linguistic measures, POS tags, and social context variables. The best models for prediction of the Consonant Updating score and the composite working memory score comprised POS tags only. CONCLUSIONS: The results suggest that machine learning and NLP may support the prediction of working memory using, in particular, linguistic measures and social context information extracted from the everyday conversations of healthy older adults. Our findings may support the design of an early warning system to be used in longitudinal studies that collects cognitive ability scores and records real-life conversations unobtrusively. This system may support the timely detection of early cognitive decline. In particular, the use of a privacy-sensitive passive monitoring technology would allow for the design of a program of interventions to enable strategies and treatments to decrease or avoid early cognitive decline.

Neuropsychological Profiles of Patients with Progressive Apraxia of Speech and Aphasia.

OBJECTIVE: To characterize and compare the neuropsychological profiles of patients with primary progressive apraxia of speech (PPAOS) and apraxia of speech with progressive agrammatic aphasia (AOS-PAA). METHOD: Thirty-nine patients with PPAOS and 49 patients with AOS-PAA underwent formal neurological, speech, language, and neuropsychological evaluations. Cognitive domains assessed included immediate and delayed episodic memory (Wechsler Memory Scale-Third edition; Logical Memory; Visual Reproduction; Rey Auditory Verbal Learning Test), processing speed (Trail Making Test A), executive functioning (Trail Making Test B; Delis-Kaplan Executive Functioning Scale - Sorting), and visuospatial ability (Rey-Osterrieth Complex Figure copy). RESULTS: The PPAOS patients were cognitively average or higher in the domains of immediate and delayed episodic memory, processing speed, executive functioning, and visuospatial ability. Patients with AOS-PAA performed more poorly on tests of immediate and delayed episodic memory and executive functioning compared to those with PPAOS. For every 1 unit increase in aphasia severity (e.g. mild to moderate), performance declined by 1/3 to 1/2 a standard deviation depending on cognitive domain. The degree of decline was stronger within the more verbally mediated domains, but was also notable in less verbally mediated domains. CONCLUSION: The study provides neuropsychological evidence further supporting the distinction of PPAOS from primary progressive aphasia and should be used to inform future diagnostic criteria. More immediately, it informs prognostication and treatment planning.

Deep multiple instance learning for foreground speech localization in ambient audio from wearable devices.

Over the recent years, machine learning techniques have been employed to produce state-of-the-art results in several audio related tasks. The success of these approaches has been largely due to access to large amounts of open-source datasets and enhancement of computational resources. However, a shortcoming of these methods is that they often fail to generalize well to tasks from real life scenarios, due to domain mismatch. One such task is foreground speech detection from wearable audio devices. Several interfering factors such as dynamically varying environmental conditions, including background speakers, TV, or radio audio, render foreground speech detection to be a challenging task. Moreover, obtaining precise moment-to-moment annotations of audio streams for analysis and model training is also time-consuming and costly. In this work, we use multiple instance learning (MIL) to facilitate development of such models using annotations available at a lower time-resolution (coarsely labeled). We show how MIL can be applied to localize foreground speech in coarsely labeled audio and show both bag-level and instance-level results. We also study different pooling methods and how they can be adapted to densely distributed events as observed in our application. Finally, we show improvements using speech activity detection embeddings as features for foreground detection.

Longitudinal clinical, neuropsychological, and neuroimaging characterization of a kindred with a 12-octapeptide repeat insertion in PRNP: the next generation.

BACKGROUND: Highly penetrant inherited mutations in the prion protein gene (PRNP) offer a window to study the pathobiology of prion disorders. METHOD: Clinical, neuropsychological, and neuroimaging characterization of a kindred. RESULTS: Three of four mutation carriers have progressed to a frontotemporal dementia phenotype. Declines in neuropsychological function coincided with changes in FDG-PET at the identified onset of cognitive impairment. CONCLUSIONS AND RELEVANCE: Gene silencing treatments are on the horizon and when they become available, early detection will be crucial. Longitudinal studies involving familial mutation kindreds can offer important insights into the initial neuropsychological and neuroimaging changes necessary for early detection.

Progressive dysexecutive syndrome due to Alzheimer's disease: a description of 55 cases and comparison to other phenotypes.

We report a group of patients presenting with a progressive dementia syndrome characterized by predominant dysfunction in core executive functions, relatively young age of onset and positive biomarkers for Alzheimer's pathophysiology. Atypical frontal, dysexecutive/behavioural variants and early-onset variants of Alzheimer's disease have been previously reported, but no diagnostic criteria exist for a progressive dysexecutive syndrome. In this retrospective review, we report on 55 participants diagnosed with a clinically defined progressive dysexecutive syndrome with 18F-fluorodeoxyglucose-positron emission tomography and Alzheimer's disease biomarkers available. Sixty-two per cent of participants were female with a mean of 15.2 years of education. The mean age of reported symptom onset was 53.8 years while the mean age at diagnosis was 57.2 years. Participants and informants commonly referred to initial cognitive symptoms as 'memory problems' but upon further inquiry described problems with core executive functions of working memory, cognitive flexibility and cognitive inhibitory control. Multi-domain cognitive impairment was evident in neuropsychological testing with executive dysfunction most consistently affected. The frontal and parietal regions which overlap with working memory networks consistently demonstrated hypometabolism on positron emission tomography. Genetic testing for autosomal dominant genes was negative in all eight participants tested and at least one APOE ε4 allele was present in 14/26 participants tested. EEG was abnormal in 14/17 cases with 13 described as diffuse slowing. Furthermore, CSF or neuroimaging biomarkers were consistent with Alzheimer's disease pathophysiology, although CSF p-tau was normal in 24% of cases. Fifteen of the executive predominate participants enrolled in research neuroimaging protocols and were compared to amnestic (n = 110), visual (n = 18) and language (n = 7) predominate clinical phenotypes of Alzheimer's disease. This revealed a consistent pattern of hypometabolism in parieto-frontal brain regions supporting executive functions with relative sparing of the medial temporal lobe (versus amnestic phenotype), occipital (versus visual phenotype) and left temporal (versus language phenotype). We propose that this progressive dysexecutive syndrome should be recognized as a distinct clinical phenotype disambiguated from behavioural presentations and not linked specifically to the frontal lobe or a particular anatomic substrate without further study. This clinical presentation can be due to Alzheimer's disease but is likely not specific for any single aetiology. Diagnostic criteria are proposed to facilitate additional research into this understudied clinical presentation.

Eavesdropping on Autobiographical Memory: A Naturalistic Observation Study of Older Adults' Memory Sharing in Daily Conversations.

The retrieval of autobiographical memories is an integral part of everyday social interactions. Prior laboratory research has revealed that older age is associated with a reduction in the retrieval of autobiographical episodic memories, and the ability to elaborate these memories with episodic details. However, how age-related reductions in episodic specificity unfold in everyday social contexts remains largely unknown. Also, constraints of the laboratory-based approach have limited our understanding of how autobiographical semantic memory is linked to older age. To address these gaps in knowledge, we used a smartphone application known as the Electronically Activated Recorder, or "EAR," to unobtrusively capture real-world conversations over 4 days. In a sample of 102 cognitively normal older adults, we extracted instances where memories and future thoughts were shared by the participants, and we scored the shared episodic memories and future thoughts for their make-up of episodic and semantic detail. We found that older age was associated with a reduction in real-world sharing of autobiographical episodic and semantic memories. We also found that older age was linked to less episodically and semantically detailed descriptions of autobiographical episodic memories. Frequency and level of detail of shared future thoughts yielded weaker relationships with age, which may be related to the low frequency of future thoughts in general. Similar to laboratory research, there was no correlation between autobiographical episodic detail sharing and a standard episodic memory test. However, in contrast to laboratory studies, episodic detail production while sharing autobiographical episodic memories was weakly related to episodic detail production while describing future events, unrelated to working memory, and not different between men and women. Overall, our findings provide novel evidence of how older age relates to episodic specificity when autobiographical memories are assessed unobtrusively and objectively "in the wild."

Natural, Everyday Language Use Provides a Window Into the Integrity of Older Adults' Executive Functioning.

OBJECTIVES: Language markers derived from structured clinical interviews and assessments have been found to predict age-related normal and pathological cognitive functioning. An important question, then, is the degree to which the language that people use in their natural daily interactions, rather than their language elicited within and specifically for clinical assessment, carries information about key cognitive functions associated with age-related decline. In an observational study, we investigated how variability in executive functioning (EF) manifests in patterns of daily word use. METHOD: Cognitively normal older adults (n = 102; mean age 76 years) wore the electronically activated recorder, an ambulatory monitoring device that intermittently recorded short snippets of ambient sounds, for 4 days, yielding an acoustic log of their daily conversations as they naturally unfolded. Verbatim transcripts of their captured utterances were text-analyzed using linguistic inquiring and word count. EF was assessed with a validated test battery measuring WM, shifting, and inhibitory control. RESULTS: Controlling for age, education, and gender, higher overall EF, and particularly working memory, was associated with analytic (e.g., more articles and prepositions), complex (e.g., more longer words), and specific (e.g., more numbers) language in addition to other language markers (e.g., a relatively less positive emotional tone, more sexual and swear words). DISCUSSION: This study provides first evidence that the words older adults use in daily life provide a window into their EF.