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The locus coeruleus-noradrenaline system regulates brain-wide neural activity involved in cognition and behavior. Integrity of this subcortical neuromodulatory system is proposed to be a substrate of cognitive reserve that may be strengthened by lifetime cognitive and social activity. Conversely, accumulation of tau tangles in the brainstem locus coeruleus nuclei is recently studied as a very early marker of Alzheimer's disease (AD) pathogenesis and cognitive vulnerability, even among older adults without cognitive impairment or significant cerebral AD pathologies. This clinical-pathologic study examined whether locus coeruleus tangle density was cross-sectionally associated with lower antemortem cognitive performance and social activity among 142 cognitively unimpaired and impaired older adults and whether social activity, a putative reserve factor, mediated the association of tangle density and cognition. We found that greater locus coeruleus tangle density was associated with lower social activity for the whole sample and in the cognitively unimpaired group alone and these associations were independent of age, sex, education, depressive symptoms, and burden of cerebral amyloid and tau. The association of locus coeruleus tangle density with lower cognitive performance was partially mediated by level of social activity. These findings implicate the locus coeruleus-noradrenaline system in late-life social function and support that locus coeruleus tangle pathology is associated with lower levels of social activity, independent of cerebral AD pathologies, and specifically among older adults who are cognitively unimpaired. Early brainstem pathology may impact social function, and level of social function, in turn, influences cognition, prior to canonical stages of AD.
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OBJECTIVE: Anxiety disorders and subsyndromal anxiety symptoms are highly prevalent in late life. Recent studies support that anxiety may be a neuropsychiatric symptom during preclinical Alzheimer's disease (AD) and that higher anxiety is associated with more rapid cognitive decline and progression to cognitive impairment. However, the associations of specific anxiety symptoms with AD pathologies and with co-occurring subjective and objective cognitive changes have not yet been established. METHODS: Baseline data from the A4 and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies were analyzed. Older adult participants (n = 4,486) underwent assessments of anxiety (State-Trait Anxiety Inventory-6 item version [STAI]), and cerebral amyloid-beta (Aß; 18F-florbetapir) PET and a subset underwent tau (18F-flortaucipir) PET. Linear regressions estimated associations of Aß in a cortical composite and tau in the amygdala, entorhinal, and inferior temporal regions with STAI-Total and individual STAI item scores. Models adjusted for age, sex, education, marital status, depression, Apolipoprotein ε4 genotype, and subjective and objective cognition (Cognitive Function Index-participant; Preclinical Alzheimer Cognitive Composite). RESULTS: Greater Aß deposition was significantly associated with higher STAI-Worry, adjusting for all covariates, but not with other STAI items or STAI-Total scores. In mediation analyses, the association of Aß with STAI-Worry was partially mediated by subjective cognition with a stronger direct effect. No associations were found for regional tau deposition with STAI-Total or STAI-Worry score. CONCLUSION: Greater worry was associated with Aß but not tau deposition, independent of subjective and objective cognition in cognitively unimpaired (CU) older adults. These findings implicate worry as an early, specific behavioral marker and a possible therapeutic target in preclinical AD.
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Péptidos beta-Amiloides , Ansiedad , Tomografía de Emisión de Positrones , Proteínas tau , Humanos , Anciano , Péptidos beta-Amiloides/metabolismo , Masculino , Femenino , Proteínas tau/metabolismo , Ansiedad/metabolismo , Anciano de 80 o más Años , Disfunción Cognitiva/metabolismo , Estudios Longitudinales , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Carbolinas , Cognición/fisiología , Compuestos de Anilina , Glicoles de EtilenoRESUMEN
Introduction: This study investigated a remotely delivered, therapist-facilitated, personalized music listening intervention for community-dwelling older adults experiencing loneliness during the Covid-19 pandemic. We assessed its feasibility and individuals' experiences of social connection and emotional well-being during the intervention. Methods: Ten cognitively unimpaired older adults who endorsed loneliness completed eight weekly sessions with a board-certified music therapist via Zoom. Participants were guided in developing two online personalized music playlists and were asked to listen to playlists for at least one hour daily. Feasibility metrics were attendance, accessibility, and compliance rates. Post-study interview responses were analyzed using a rapid qualitative methodology. Exploratory pre- and post-study measures of loneliness and other aspects of psychological well-being were obtained using validated questionnaires. Results: Ten participants (mean age 75.38 [65 to 85] years, 80% women) were enrolled from March to August 2021. Attendance and compliance rates were 100% and the accessibility rate was 90%. Most participants associated music with positive memories before the program and many reported that the intervention prompted them to reconnect with music or listen to music with greater intention. They cited increased connection from interacting with the music therapist and the music itself, as well as specific positive emotional impacts from integrating music into their daily lives. Median pre- to post-questionnaire measures of psychological function all changed in an improved direction. Discussion: Remotely delivered music therapy may be a promising intervention to promote regular music listening and socioemotional well-being in lonely older adults.
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COVID-19 , Soledad , Musicoterapia , Humanos , Musicoterapia/métodos , Anciano , Femenino , Masculino , COVID-19/psicología , Soledad/psicología , Proyectos Piloto , Anciano de 80 o más Años , Estudios de Factibilidad , SARS-CoV-2RESUMEN
The intrinsic organization of functional brain networks is known to change with age, and is affected by perceptual input and task conditions. Here, we compare functional activity and connectivity during music listening and rest between younger (n = 24) and older (n = 24) adults, using whole-brain regression, seed-based connectivity, and ROI-ROI connectivity analyses. As expected, activity and connectivity of auditory and reward networks scaled with liking during music listening in both groups. Younger adults show higher within-network connectivity of auditory and reward regions as compared with older adults, both at rest and during music listening, but this age-related difference at rest was reduced during music listening, especially in individuals who self-report high musical reward. Furthermore, younger adults showed higher functional connectivity between auditory network and medial prefrontal cortex that was specific to music listening, whereas older adults showed a more globally diffuse pattern of connectivity, including higher connectivity between auditory regions and bilateral lingual and inferior frontal gyri. Finally, connectivity between auditory and reward regions was higher when listening to music selected by the participant. These results highlight the roles of aging and reward sensitivity on auditory and reward networks. Results may inform the design of music-based interventions for older adults and improve our understanding of functional network dynamics of the brain at rest and during a cognitively engaging task.
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Imagen por Resonancia Magnética , Música , Humanos , Anciano , Encéfalo/diagnóstico por imagen , Envejecimiento , Mapeo Encefálico/métodos , Recompensa , Percepción AuditivaRESUMEN
OBJECTIVE: Volunteer organizations offer telephone outreach to older adults to relieve feelings of loneliness and to promote emotional well-being, though the feasibility, perceived value, and characteristics of the participant experience of these community interventions have not been well-studied. We examined these elements of an intergenerational college-based telephone call program during the Covid-19 pandemic. METHODS: Community-dwelling older adults and undergraduate volunteers engaged in eight, weekly, 30-minute, unscripted telephone conversations. Feasibility criteria included enrollment, retention, and attendance rates. A rapid qualitative analysis of program evaluation responses was used to extract themes related to participants' experiences of the intervention. RESULTS: Ten older adults (mean age [range] 74.53 [70-84] years, 88% women) and nine undergraduates were enrolled from February to August 2021, achieving recruitment targets and enrollment rates of 76.9% and 90%. Seven out of the 10 enrolled dyads completed the full series of eight telephone conversations and qualitative assessments over an average of 10.5 weeks. Most older adults who completed the call schedule valued the conversations as a source of social connection, noting the mutuality, respect, and broadened perspective that characterized their intergenerational relationships. Undergraduates described value in giving to others and in conversations that stimulated personal reflection and feelings of closeness. Undergraduates frequently described their experience as novel and broadening of their perspectives. CONCLUSION: Though study completion rate and participant experience varied across dyads, we found qualitative evidence of perceived value, active relationship-building and broadened perspectives among many older adults and undergraduates who completed an intergenerational telephone program.
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COVID-19 , Humanos , Femenino , Anciano , Masculino , Apoyo Social , Estudios de Factibilidad , Pandemias , TeléfonoRESUMEN
The loss of a spouse is a common and natural life event for older adults. Nearly one of four older bereaved spouses experience prolonged grief, impaired function or chronic depression. Mechanisms underlying these and other long-term health risks are not well understood. We conducted a scoping literature review to examine the interventions and outcomes that have been studied for late-life spousal bereavement to date. We identified 22 studies of group and individual-level interventions with most studies concerning grief processes within the first year. Nearly all studies evaluated emotional and psychological symptoms of loss and a small number evaluated the restoration of adaptive functioning. Four interventions addressed the treatment of complicated grief or grief with major depressive disorder. Qualitative studies explored themes of spirituality and mindfulness. There were 17 controlled studies, including 13 randomized controlled trials. Findings were eclectic, with evidence supporting mindfulness techniques in a group format for emotional and life satisfaction outcomes; an individual, function-based therapy addressing sleep to improve emotion and function; an individual, writing-based emotional expression therapy for short-term improvement in emotion and function; nortriptyline for the treatment of bereavement-related major depressive disorder; a group-based, complicated grief therapy for this condition; an internet-based CBT intervention for prolonged grief; and pharmacotherapy for cardiovascular changes during bereavement. These findings highlight the small literature of methodologically strong intervention studies addressing spousal bereavement in older adults and the need for greater exploration of relevant biological, social, cognitive and behavioral factors to improve short and long term health outcomes.
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Aflicción , Trastorno Depresivo Mayor , Adaptación Psicológica , Anciano , Depresión/psicología , Trastorno Depresivo Mayor/terapia , Pesar , Humanos , Esposos/psicologíaRESUMEN
Mild cognitive impairment (MCI) is a syndrome defined by objective cognitive deficits that do not impact functional independence. Individuals with MCI develop dementia at an annual rate of 10 to 15%. Neuropsychiatric symptoms (NPS) are common non-cognitive features of neurocognitive disorders and have a major impact on the wellbeing and quality of life of affected individuals and their families. Non-pharmacological interventions for NPS are considered the first-line treatment because of the limited efficacy and side-effect potential of current pharmacological agents. This article summarizes the literature on non-pharmacological treatments for NPS in MCI. The limited number of studies specific to individuals with MCI and its various etiologies, as well as the overall heterogeneity of research design and methodologies, make the evidence base inconclusive. Nevertheless, some studies support psychosocial interventions aimed at individuals with MCI and their caregivers.
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Trastornos del Conocimiento , Disfunción Cognitiva , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/terapia , Humanos , Pruebas Neuropsicológicas , Calidad de VidaRESUMEN
This Article was originally published under Nature Research's License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
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Late-life anxiety has been associated with increased progression from normal cognition to amnestic MCI, suggesting that anxiety may be a neuropsychiatric symptom of Alzheimer's disease (AD) pathological changes and a possible marker of anatomical progression in preclinical AD. This study examined whether cortical or subcortical amyloidosis, indicating earlier or later stages of preclinical AD, was associated with greater self-reported anxiety among 118 cognitively normal volunteers, aged 65-90 years, and whether this association was stronger in APOEε4 carriers. Participants underwent Pittsburgh Compound B Positron Emission Tomography (PiB-PET) to assess fibrillar amyloid-ß burden in cortical and subcortical regions, and measurement of anxiety using the Hospital Anxiety and Depression Scale-anxiety subscale. Higher PiB-PET measures in the subcortex (striatum, amygdala, and thalamus), but not in the cortex, were associated with greater anxiety, adjusting for demographics, cognition, and depression. Findings were similar using a cortico-striatal staging system and continuous PET measurements. Anxiety was highest in APOEε4 carriers with subcortical amyloidosis. This work supports in vivo staging of amyloid-ß deposition in both cortical and subcortical regions as a promising approach to the study of neuropsychiatric symptoms such as anxiety in cognitively normal older individuals. Elevated anxiety symptoms in combination with high-risk biological factors such as APOEε4 and subcortical amyloid-ß may identify participants closest to MCI for secondary prevention trials.
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Amiloidosis/complicaciones , Ansiedad/complicaciones , Salud , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/prevención & control , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/metabolismo , Amiloidosis/diagnóstico por imagen , Amiloidosis/metabolismo , Amiloidosis/psicología , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Femenino , Humanos , Masculino , Tomografía de Emisión de PositronesRESUMEN
Judgments of learning (JOL) pertain to introspective metamemory processes evaluating how well information is learned. Using a functional magnetic resonance imaging (fMRI) task, we investigated the neural substrates of JOL predictions in a group of 105 cognitively unimpaired older adults from the Harvard Aging Brain Study. Associations of JOL performance and its neural correlates with amyloid-ß (Aß) and tau pathology, two proteinopathies associated with Alzheimer's disease (AD) and aging, were also examined. We found that trials judged as learned well relative to trials judged as learned less well (high JOL > low JOL) engaged the ventromedial prefrontal cortex and precuneus, among other midline regions, in addition to bilateral hippocampi. In this cohort of older adults, greater levels of entorhinal tau deposition were associated with overestimation of memory performance and with lower fMRI signal in midline regions during predicted memory success. No associations with Aß were found. The findings suggest that tau pathology in unimpaired older adults may play a role in altered metamemory processes. We discuss our findings in light of the hypothesis that JOLs are partially dependent on a process involving attempts to retrieve a correct answer from memory, as well as implications for clinical research investigating unawareness of memory performance (i.e., anosognosia) in patients with AD dementia.
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Envejecimiento/patología , Enfermedad de Alzheimer/patología , Encéfalo/fisiopatología , Juicio/fisiología , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Enfermedad de Alzheimer/fisiopatología , Encéfalo/patología , Cognición/fisiología , Femenino , Humanos , Aprendizaje/fisiología , Masculino , Memoria/fisiología , Proteínas tau/metabolismoRESUMEN
OBJECTIVES: Amyloid-beta (Aß) and tau pathologies are commonly observed among clinically normal older individuals at postmortem and can now be detected with in vivo neuroimaging. The association and interaction of these proteinopathies with prospective cognitive decline in normal aging and preclinical Alzheimer's disease (AD) remains to be fully elucidated. METHODS: One hundred thirty-seven older individuals (age = 76.3 ± 6.22 years) participating in the Harvard Aging Brain Study underwent Aß (11 C-Pittsburgh compound B) and tau (18 F-flortaucipir) positron emission tomography (PET) with prospective neuropsychological assessments following PET imaging (mean number of cognitive visits = 2.8 ± 1.1). Tau and Aß PET measures were assessed in regions of interest (ROIs) as well as vertex-wise map analyses. Cognitive change was evaluated with Memory and Executive Function composites. RESULTS: Higher levels of Aß and tau were both associated with greater memory decline, but not with change in executive function. Higher cortical Aß was associated with higher tau levels in all ROIs, independent of age, and very elevated levels of tau were observed primarily in clinically normal with elevated Aß. A significant interaction between tau and Aß was observed in both ROI and map-level analyses, such that rapid prospective memory decline was observed in participants who had high levels of both pathologies. INTERPRETATION: Our results are consistent with the supposition that both Aß and tau are necessary for memory decline in the preclinical stages of AD. These findings may be relevant for disambiguating aging and early cognitive manifestations of AD, and to inform secondary prevention trials in preclinical AD. Ann Neurol 2019;00:1-3 ANN NEUROL 2019;85:181-193.
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Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Memoria Episódica , Proteínas tau/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Masculino , Tomografía de Emisión de Positrones/métodosRESUMEN
The authors of this review both served on the National Academy of Science, Engineering, and Medicine Committee that produced the report, "Social Isolation and Loneliness in Older Adults: Opportunities for the Health Care System." In 2018, the AARP Foundation commissioned the National Academies to establish a committee to research and develop a report on social isolation and loneliness in persons 50 years of age and older. Emphasis was placed upon the role of the healthcare system in addressing this fundamental public health problem. The committee released the report in February 2020 as the Corona Virus Disease 2019 pandemic was beginning to spread to North America. In this review, the authors share central findings and conclusions from the report as well as how these findings may be relevant to the care and well-being of older adults during this historic pandemic. The health protective benefits of social distancing must be balanced by the essential need for sustaining social relationships.
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COVID-19 , Soledad , Anciano , Humanos , Pandemias , SARS-CoV-2 , Aislamiento SocialRESUMEN
OBJECTIVE: Public health recommendations promote social engagement to reduce risk of cognitive decline and dementia. The objective of this study was to evaluate the longitudinal associations of social engagement and cognition in cognitively normal older adults with varying levels of neocortical amyloid-ß, the Alzheimer's disease (AD) pathologic marker. METHODS: Two hundred seventeen men and women, age 63-89 underwent assessments for social engagement and cognitive performance at baseline and 3 years later using the Community Healthy Activities Model Program for Seniors questionnaire and the Preclinical Alzheimer Cognitive Composite (PACC). Amyloid-ß was measured using Pittsburgh compound B-PET. Multivariable regression models estimated main and interactive effects of baseline social engagement and amyloid-ß on cognitive change. Reciprocal models estimated main and interactive effects of baseline cognitive performance and amyloid-ß on change in social engagement. RESULTS: Baseline social engagement was associated with PACC change as a modifier but not as a main effect. Lower baseline social engagement was associated with greater amyloid-ß-related PACC decline, while higher baseline social engagement was associated with relative preservation of PACC scores (ßâ¯=â¯0.05, pâ¯=â¯0.03). Reciprocally, lower baseline PACC score was associated with decline in social engagement score (ßâ¯=â¯1.1, pâ¯=â¯0.02). This association was not modified by amyloid-ß, and there was no direct association of amyloid-ß with change in social engagement. CONCLUSIONS: Low social engagement may be a marker of neurocognitive vulnerability in older adults who are cognitively normal but have evidence of AD pathophysiologic change. Understanding changes in social engagement in older adults may lead to earlier diagnosis of AD and advances in evidence-based prevention and treatment.
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Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/diagnóstico , Participación Social/psicología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pruebas Neuropsicológicas , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVE: To investigate the relationship of awareness of and concern about memory performance to progression from mild cognitive impairment (MCI) to Alzheimer disease (AD) dementia. METHODS: Participants (n = 33) had a diagnosis of MCI at baseline and a diagnosis of MCI or AD dementia at follow-up. Participants were categorized as "Stable-MCI" if they retained an MCI diagnosis at follow-up (mean follow-up = 18.0 months) or "Progressor-MCI" if they were diagnosed with AD dementia at follow-up (mean follow-up = 21.6 months). Awareness was measured using the residual from regressing a participant's objective memory score onto their subjective complaint score (i.e., residual<0 indicates overestimation of performance). Concern was assessed using a questionnaire examining the degree of concern when forgetting. Logistic regression was used to determine whether the presence of these syndromes could predict future diagnosis of AD dementia, and repeated measures analysis of covariance tests were used to examine longitudinal patterns of these syndromes. RESULTS: Baseline anosognosia was apparent in the Progressor-MCI group, whereas participants in the Stable-MCI group demonstrated relative awareness of their memory performance. Baseline awareness scores successfully predicted whether an individual would progress to AD-dementia. Neither group showed change in awareness of performance over time. Neither group showed differences in concern about memory performance at baseline or change in concern about performance over time. CONCLUSION: These data suggest that anosognosia may appear prior to the onset of AD dementia, while anosodiaphoria likely does not appear until later in the AD continuum. Additionally, neither group showed significant changes in awareness or concern over time, suggesting that change in these variables may happen over longer periods.
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Enfermedad de Alzheimer/psicología , Ansiedad/psicología , Concienciación , Disfunción Cognitiva/psicología , Progresión de la Enfermedad , Memoria , Anciano , Agnosia/complicaciones , Agnosia/psicología , Enfermedad de Alzheimer/complicaciones , Disfunción Cognitiva/complicaciones , Femenino , Humanos , Masculino , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Affective and emotional symptoms such as depression, anxiety, euphoria, and irritability are common neuropsychiatric symptoms (NPS) in pre-dementia and cognitively normal older adults. They comprise a domain of Mild Behavioral Impairment (MBI), which describes their emergence in later life as an at-risk state for cognitive decline and dementia, and as a potential manifestation of prodromal dementia. This selective scoping review explores the epidemiology and neurobiological links between affective and emotional symptoms, and incident cognitive decline, focusing on recent literature in this expanding field of research. METHODS: Existing literature in prodromal and dementia states was reviewed, focusing on epidemiology, and neurobiology. Search terms included: "mild cognitive impairment," "dementia," "prodromal dementia," "preclinical dementia," "Alzheimer's," "depression," "dysphoria," "mania," "euphoria," "bipolar disorder," and "irritability." RESULTS: Affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often being harbingers of neurodegenerative change and progressive cognitive decline. Nosological constraints in distinguishing between pre-existing psychiatric symptomatology and later life acquired NPS limit historical data utility, but emerging research emphasizes the importance of addressing time frames between symptom onset and cognitive decline, and age of symptom onset. CONCLUSION: Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies.
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Ansiedad/psicología , Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Depresión/psicología , Euforia , Genio Irritable , Síntomas Afectivos , Anciano , Disfunción Cognitiva/psicología , Demencia/complicaciones , Emociones , Humanos , Pruebas Neuropsicológicas , Evaluación de SíntomasRESUMEN
INTRODUCTION: Amyloid positron emission tomography (PET) data are commonly expressed as binary measures of cortical deposition. However, not all individuals with high cortical amyloid will experience rapid cognitive decline. Motivated by postmortem data, we evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on cortical measures. METHODS: We classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition. RESULTS: Follow-up data indicated that PET detects amyloid first in cortex and then in striatum. Our three-category staging including striatum better predicted hippocampal volumes and subsequent cognition than a three-category staging including only cortical amyloid. DISCUSSION: PET can evaluate amyloid expansion from cortex to subcortex. Using striatal signal as a marker of advanced amyloidosis may increase predictive power in Alzheimer's dementia research.
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Amiloidosis/diagnóstico por imagen , Cuerpo Estriado/diagnóstico por imagen , Tomografía de Emisión de Positrones , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Amiloidosis/genética , Amiloidosis/metabolismo , Apolipoproteína E4/genética , Conmoción Encefálica/diagnóstico por imagen , Conmoción Encefálica/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/genética , Disfunción Cognitiva/metabolismo , Cuerpo Estriado/metabolismo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Interpretación de Imagen Asistida por Computador , Estudios Longitudinales , Masculino , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: Apathy is among the earliest and most pervasive neuropsychiatric symptoms in prodromal and mild Alzheimer disease (AD) dementia that correlates with functional impairment and disease progression. We investigated the association of apathy with regional 18F-fluorodeoxyglucose (FDG) metabolism in cognitively normal, mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative database. DESIGN: Cross-sectional and longitudinal studies. SETTING: 57 North American research sites. PARTICIPANTS: 402 community dwelling elders. MEASUREMENTS: Apathy was assessed using the Neuropsychiatric Inventory Questionnaire. Baseline FDG metabolism in five regions implicated in the neurobiology of apathy and AD was investigated in relationship to apathy at baseline (cross-sectional general linear model) and longitudinally (mixed random/fixed effect model). Covariates included age, sex, diagnosis, apolipoprotein E genotype, premorbid intelligence, cognition, and antidepressant use. RESULTS: Cross-sectional analysis revealed that posterior cingulate hypometabolism, diagnosis, male sex, and antidepressant use were associated with higher apathy scores. Longitudinal analysis revealed that the interaction of supramarginal hypometabolism and time, posterior cingulate hypometabolism, and antidepressant use were associated with higher apathy scores across time; only supramarginal hypometabolism was positively related to rate of increase of apathy. CONCLUSIONS: Results support an association of apathy with hypometabolism in parietal regions commonly affected in early stages of AD, rather than medial frontal regions implicated in the neurobiology of apathy in later stages. Further work is needed to substantiate whether this localization is specific to apathy rather than to disease stage, and to investigate the potential role of AD proteinopathies in the pathogenesis of apathy.
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Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/psicología , Apatía , Disfunción Cognitiva/metabolismo , Lóbulo Parietal/metabolismo , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Fluorodesoxiglucosa F18/metabolismo , Neuroimagen Funcional , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos/metabolismoRESUMEN
OBJECTIVE: To examine reciprocal relations of loneliness and cognitive function in older adults. METHODS: Data were analyzed from 8382 men and women, age 65 and older, participating in the US Health and Retirement Study from 1998 to 2010. Participants underwent biennial assessments of loneliness and depression (classified as no, low or high depression) determined by the Center for Epidemiologic Studies Depression scale (8-item version), cognition (a derived memory score based on a word list memory task and proxy-rated memory and global cognitive function), health status and social and demographic characteristics from 1998 to 2010. We used repeated measures analysis to examine the reciprocal relations of loneliness and cognitive function in separate models controlling sequentially and cumulatively for socio-demographic factors, social network, health conditions and depression. RESULTS: Loneliness at baseline predicted accelerated cognitive decline over 12 years independent of baseline socio-demographic factors, social network, health conditions and depression (ß = -0.2, p = 0.002). After adjustment for depression interacting with time, both low and high depression categories were related to faster cognitive decline and the estimated effect of loneliness became marginally significant. Reciprocally, poorer cognition at baseline was associated with greater odds of loneliness over time in adjusted analyses (OR 1.3, 95% CI (1.1-1.5) p = 0.005), but not when controlling for baseline depression. Furthermore, cognition did not predict change in loneliness over time. CONCLUSION: Examining longitudinal data across a broad range of cognitive abilities, loneliness and depressive symptoms appear to be related risk factors for worsening cognition but low cognitive function does not lead to worsening loneliness over time. Copyright © 2016 John Wiley & Sons, Ltd.
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Disfunción Cognitiva/psicología , Trastorno Depresivo/psicología , Soledad/psicología , Anciano , Anciano de 80 o más Años , Demografía , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
INTRODUCTION: Sensitive detection of cognitive decline over the course of preclinical Alzheimer's disease is critical as the field moves toward secondary prevention trials. METHODS: We examined amyloid ß (Aß)-related change in several variations of the preclinical Alzheimer cognitive composite (PACC) and each individual PACC component in clinically normal (CN) older participants in the Harvard Aging Brain Study. We then examined the PACC variations in the Alzheimer's Disease Cooperative Study Prevention Instrument Study as a replication cohort. RESULTS: Aß+ CN individuals demonstrated longitudinal decline on all individual PACC components and all PACC variations. Aß group differences emerged earlier when Free and Cued Selective Reminding Test Free Recall was included in the PACC. PACC decline was associated with Clinical Dementia Rating progression. DISCUSSION: This independent data set and a replication cohort confirm the ability of the PACC to capture both early and late cognitive decline during the preclinical stages of Alzheimer's disease, which may prove advantageous in the prevention trial design.