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IntroductionWe investigated the association between sleep duration and neuropathologic changes 19 to 40 years later in oldest-old (age 90+) participants of The 90+ Study.MethodsParticipants self-reported sleep duration and underwent neuropathologic evaluation. We categorized sleep duration as < 7, 7 to 8 = reference, > 8 hours and dichotomized neuropathologic changes as present/absent. We estimated odds ratio (OR) and 95% confidence intervals (CI) using logistic regression.ResultsIn 264 participants, mean age at sleep self-report was 69 years, mean age at autopsy was 98 years, and mean interval between sleep self-report and autopsy was 29 years (range: 19-40). Those reporting > 8 hours of sleep had lower likelihood of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) inclusions (OR = 0.18; CI = 0.04-0.82) and amyloid beta deposits (OR = 0.34; 95% CI = 0.12-0.94).DiscussionLong self-reported sleep is associated with lower odds of neurodegenerative neuropathologic changes 19 to 40 years later in the oldest-old, suggesting a potential role of sleep in accumulation of dementia-related neuropathologies.HighlightsAssociation of self-reported sleep with non-Alzheimer's disease neuropathologic changes has not been explored. Whether sleep duration is related to dementia neuropathologic changes decades later is unclear. Long self-reported sleep is associated with lower odds of Alzheimer's disease neuropathologic change 19 to 40 years later in the oldest-old. Long self-reported sleep is associated with lower odds of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change 19 to 40 years later in the oldest-old.

Successful cognitive aging is often thought to result from resistance to the accumulation of pathology, resilience to the effects of pathological accumulation, or some combination of the two. While evidence for resilience has been found in typical aging populations, the oldest-old provide us with a unique window into the role of pathological accumulation in impacting cognition. Here, we aimed to assess group differences in measures of amyloid and tau across older age groups using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI age: 60-89) and The 90+ Study (age: 90-101). Additionally, using the ADNI dataset, we performed exploratory analyses of regional cingulate AV-45 SUVRs to assess if amyloid load in particular areas was associated with Top Cognitive Performance (TCP). Consistent with the literature, results showed no group differences in amyloid SUVRs both regionally and in the whole cortex. For tau with AV-1451, we also observed no differences in Braak composite SUVRs. Interestingly, these relationships persisted in the oldest-old. This indicates that Top Cognitive Performance throughout aging does not reflect resistance to amyloid and tau burden, but that other mechanisms may be associated with protection against amyloid and tau related neurodegeneration.

BackgroundSome oldest-old individuals can maintain superior cognition despite advanced age. Little is known about the neuropathological changes in the brains of oldest-old superior cognitive performers.ObjectiveOur objective was to examine the associations between Alzheimer's disease (AD) and non-AD neuropathologic features in relation to superior cognitive performance in oldest-old individuals.MethodsWe analyzed brain autopsy data from 102 participants with normal cognition from The 90+ Study. Superior global cognitive performers (SGCP) were defined as having Mini-Mental State Examination (MMSE) score ≥28 in the last visit 12 to 2 months before death. To examine the associations between individual and multiple comorbid neuropathologic features with SGCP status we used multiple logistic regression models adjusting for age, sex, and education.ResultsAlzheimer's disease neuropathological change (ADNC) and low levels of vascular pathologic change were not associated with superior cognition. In contrast, participants with limbic (OR = 8.37; 95% CI: 1.48-47.44) and neocortical (OR = 10.80;95% CI: 1.03-113.82) Lewy body disease (LBD), or with hippocampal sclerosis (HS) (OR = 5.28; 95% CI: 1.10-25.47) were more likely to be non-SGCP. High total burden of multiple comorbid neuropathologic features was associated with a lower likelihood of being SGCP.ConclusionOldest-old superior cognitive performers were resilient to ADNC and low levels of vascular pathologic change and were resistant to non-AD neurodegenerative changes and multiple comorbid neuropathologic features. Understanding the factors underlying the ability of superior cognitive performers to resist these changes might provide useful insights on maintenance of superior cognition despite advanced age.

Hippocampal sclerosis of aging (HS-A) is a common age-related neuropathological lesion characterized by neuronal loss and astrogliosis in subiculum and CA1 subfield of hippocampus. HS-A is associated with cognitive decline that mimics Alzheimer's disease. Pathological diagnosis of HS-A is traditionally binary based on presence/absence of the lesion. We compared this traditional measure against our novel quantitative measure for studying the relationship between HS-A and other neuropathologies and cognitive impairment. We included 409 participants from The 90+ study with neuropathological examination and longitudinal neuropsychological assessments. In those with HS-A, we examined digitized H&E and LFB stained hippocampal slides. The length of HS-A in each subfield of hippocampus and subiculum, each further divided into three subregions, was measured using Aperio eSlide Manager. For each subregion, the proportion affected by HS-A was calculated. Using regression models, both traditional/binary and quantitative measures were used to study the relationship between HS-A and other neuropathological changes and cognitive outcomes. HS-A was present in 48 (12%) of participants and was always focal, primarily affecting CA1 (73%), followed by subiculum (9%); overlapping pathology (subiculum and CA1) affected 18% of individuals. HS-A was more common in the left (82%) than the right (25%) hemisphere and was bilateral in 7% of participants. HS-A traditional/binary assessment was associated with limbic-predominant age-related TDP-43 encephalopathy (LATE-NC; OR = 3.45, p < 0.001) and aging-related tau astrogliopathy (ARTAG; OR = 2.72, p = 0.008). In contrast, our quantitative approach showed associations between the proportion of HS-A (CA1/subiculum/combined) and LATE-NC (p = 0.001) and arteriolosclerosis (p = 0.005). While traditional binary assessment of HS-A was associated with impaired memory (OR = 2.60, p = 0.007), calculations (OR = 2.16, p = 0.027), and orientation (O

BackgroundThough dementia rates vary by racial or ethnic groups, it is unknown if these disparities remain among those aged 90 or older.AimsTo test this hypothesis, we used baseline clinical evaluation of 541 ethnically and racially diverse individuals participating in the LifeAfter90 Study to assess how associations between core demographic characteristics and measures of physical and cognitive performance differ across the racial/ethnic groups.MethodsParticipants in this study were long-term non-demented members of Kaiser Permanente Northern California. They were clinically evaluated and diagnosed with normal or impaired cognition (mild cognitive impairment and dementia) through an in-person comprehensive clinical assessment consisting of a detailed medical history, physical and neurological examination, functional, and cognitive tests.ResultsThe average age at enrollment was 93.0 ± 2.6 years, 62.4% female and 34.2% non-Hispanic White. At initial evaluation 301 participants had normal cognition and 165 had mild cognitive impairment (MCI) and despite screening, 69 participants were determined to have dementia. Age, education, 3MS, FAQ and CDR scores were significantly associated with cognitive impairment (normal versus MCI and dementia), but not gender. There was a significant univariate association between race/ethnicity and cognitive impairment (p < 0.02) being highest among Black (57.4%) and lowest among Asian (32.7%) individuals. After adjustment for age, gender, and education, however, prevalence of cognitive impairment was not influenced by race or ethnicity.ConclusionOur results confirm the ability to reliably assess clinical diagnosis in a diverse sample of very old individuals.

Objectives: Oldest-old patients may have an unusual SARS-COV2 presentation that can jeopardise diagnosis and management. The aim of this study was to compare the clinical characteristics and outcomes of oldest-old (≥85 years) and old patients (75–85 years) admitted with COVID-19 to Belgian hospitals during the first wave of the pandemic. Methods: We conducted a multicentre, retrospective, observational study in ten Belgian hospitals. We reviewed the electronic clinical records of patients ≥75 years hospitalised with COVID-19 from March to June 2020. Results: A total of 986 patients were placed on the register (old group: n = 507; oldest-old group: n = 479). Before hospitalisation, the oldest-old (OO) group presented with more geriatric syndromes including comorbidities, frailty, falls, cognitive impairment, and incontinence. At admission, the OO group presented with less cough, less headache, and less fever but significantly more delirium than old (O) group. Members of the OO group were admitted less frequently to intensive care units (ICUs). A geriatrician was consulted to help in the decision-making process more often for the OO group. The global mortality of the cohort was 47%, with no difference between the two groups. Patients in the OO group were more often institutionalised after hospitalisation and less often referred for rehabilitation. Conclusions: The OO patients presented with more geriatric syndromes that make them vulnerable to dependence and institutionalisation after a hospital stay, without having a higher mortality rate than O patients. Geriatrician expertise is necessary in the management of frail older patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Older adults 75 and above are a fast-growing segment of the population. However, few studies have investigated what it means to age successfully from their perspective. This group of older adults face challenges that might characteristically differ from younger older adults. Therefore, the aim of this study was to conduct a systematic review of the perspectives of older adults aged 75 and above regarding what it means to age successfully and to summarise the findings through a narrative synthesis. We also aimed to provide a snapshot of inhibitors and facilitators to achieve successful ageing. A systematic review of the 75+ older adults’ perspectives was conducted across PubMed, CINAHL, Scopus, Web of Science and PsycINFO. Qualitative, quantitative and mixed-methods original peer-reviewed studies were included. After reviewing 4,661 articles, 15 articles met the inclusion criteria and 15 themes were identified. They ranged from biomedical components such as physical functioning to psychosocial components such as relationships, reflections on life and past experiences, preparations for death and environmental factors. The findings revealed that as people age, their definition of successful ageing changes, expanding the current conceptualisation of successful ageing by including additional factors that can act as facilitators and/or inhibitors, such as death and environmental factors. The findings also highlight the need for further research on theory development by considering age-related differences and the perspectives of under-studied populations.

The number of individuals experiencing age-related cognitive decline will increase as the population of older adults continues to rise, with the fastest growing segment being oldest-old adults aged 85+ years. These cognitive deficits can be at least partly attributed to age-related declines in the underlying neural substrates (e.g., white matter microstructure), which can be measured in living individuals using magnetic resonance imaging (MRI). However, MRI studies examining the association between cognitive and brain aging across the older adult lifespan rarely use samples that extend into advanced age. To address this limitation, this dissertation studied neurocognitive aging within oldest-old adults using diffusion MRI and integrative review methodologies. Chapter 1 used traditional single tensor diffusion imaging to examine the linearity of age-related declines in white matter microstructure across 108 adults ages 65-98 years. Results indicated accelerated brain-wide white matter microstructure declines into advanced age, with declines in medial temporal white matter mediating the negative effect of age on episodic memory performance. Chapter 2 used more advanced multicompartment diffusion imaging to assess relations between white matter microstructure and associative learning performance within a subset of 22 oldest-old adults from Chapter 1. Results indicated preserved associative learning abilities into the 10th decade of life that were supported by better microstructure of white matter connections between the prefrontal cortex and dorsal striatum. Findings from Chapters 1 and 2 were independent of diagnoses of cognitive impairment no dementia in oldest-old adults, suggesting that they were not driven by advanced age-related cognitive dysfunction. Finally, Chapter 3 examined whether these findings align with those from other MRI studies of oldest-old adults as well as predictions of select neurocognitive aging theories. Despite there being some continuity acr

Advanced old age has been characterized as a biologically highly vulnerable life phase. Biological, morbidity-, and cognitive impairment-related factors play an important role as mortality predictors among very old adults. However, it is largely unknown whether previous findings confirming the role of different wellbeing domains for mortality translate to survival among the oldest-old individuals. Moreover, the distinction established in the wellbeing literature between hedonic and eudaimonic wellbeing as well as the consideration of within-person variability of potentially relevant mortality predictors has not sufficiently been addressed in prior mortality research. In this study, we examined a broad set of hedonic and eudaimonic wellbeing indicators, including their levels, their changes, as well as their within-person variability, as predictors of all-cause mortality in a sample of very old individuals. We used data from the LateLine study, a 7-year longitudinal study based on a sample of n = 124 individuals who were living alone and who were aged 87–97 years (M = 90.6, SD = 2.9) at baseline. Study participants provided up to 16 measurement occasions (mean number of measurement occasions per individual = 5.50, SD = 4.79) between 2009 and 2016. Dates of death were available for 118 individuals (95.2%) who had deceased between 2009 and 2021. We ran longitudinal multilevel structural equation models and specified between-person level differences, within-person long-term linear change trends, as well as the “detrended” within-person variability in three indicators of hedonic (i.e., life satisfaction and positive and negative affect) and four indicators of eudaimonic wellbeing (i.e., purpose in life, autonomy, environmental mastery, and self-acceptance) as all-cause mortality predictors. Controlling for age, gender, education, and physical condition and testing our sets of hedonic and eudaimonic indictors separately in terms of their mortality impact, solely one eudai, Peer Reviewed

Oldest-old patients may have an unusual SARS-COV2 presentation that can jeopardise diagnosis and management. The aim of this study was to compare the clinical characteristics and outcomes of oldest-old (≥85 years) and old patients (75-85 years) admitted with COVID-19 to Belgian hospitals during the first wave of the pandemic. We conducted a multicentre, retrospective, observational study in ten Belgian hospitals. We reviewed the electronic clinical records of patients ≥75 years hospitalised with COVID-19 from March to June 2020. A total of 986 patients were placed on the register (old group: n = 507; oldest-old group: n = 479). Before hospitalisation, the oldest-old (OO) group presented with more geriatric syndromes including comorbidities, frailty, falls, cognitive impairment, and incontinence. At admission, the OO group presented with less cough, less headache, and less fever but significantly more delirium than old (O) group. Members of the OO group were admitted less frequently to intensive care units (ICUs). A geriatrician was consulted to help in the decision-making process more often for the OO group. The global mortality of the cohort was 47%, with no difference between the two groups. Patients in the OO group were more often institutionalised after hospitalisation and less often referred for rehabilitation. The OO patients presented with more geriatric syndromes that make them vulnerable to dependence and institutionalisation after a hospital stay, without having a higher mortality rate than O patients. Geriatrician expertise is necessary in the management of frail older patients.

Cognitive resilience provides insights into maintaining good cognition despite dementia-related neuropathologic changes. It is of special interest in the oldest-old (age 90+) because age is the strongest risk factor for dementia. We describe the only participant of The 90+ Study, among 367 autopsies, who maintained normal cognition despite intermediate-high levels of 3 dementia-related neuropathologic changes, advanced age, and comorbidities associated with cognitive impairment. This man remained cognitively normal throughout 13 semi-annual study visits, last one being 4 months before his death at 96. His cognitive test scores remained around the 90th percentile for non-timed tests and declined from 90th to 50th percentile (significant for semantic fluency) for timed tests. He remained physically and cognitively active until death, despite extrapyramidal signs in the last year of life. Neuropathological examination revealed intermediate level of Alzheimer's disease neuropathologic change (Thal phase 5, Braak NFT stage IV, CERAD score 3), Lewy bodies and neurites in the olfactory bulb, brainstem and limbic areas (Braak PD stage 4), TDP-43 inclusions in the amygdala and hippocampus (LATE stage 2), and a microvascular lesion in putamen. This case demonstrates that cognitive impairment is not inevitable even in the oldest-old with mutltiple dementia-related neuropathologic changes.

The number of individuals experiencing age-related cognitive decline will increase as the population of older adults continues to rise, with the fastest growing segment being oldest-old adults aged 85+ years. These cognitive deficits can be at least partly attributed to age-related declines in the underlying neural substrates (e.g., white matter microstructure), which can be measured in living individuals using magnetic resonance imaging (MRI). However, MRI studies examining the association between cognitive and brain aging across the older adult lifespan rarely use samples that extend into advanced age. To address this limitation, this dissertation studied neurocognitive aging within oldest-old adults using diffusion MRI and integrative review methodologies. Chapter 1 used traditional single tensor diffusion imaging to examine the linearity of age-related declines in white matter microstructure across 108 adults ages 65-98 years. Results indicated accelerated brain-wide white matter microstructure declines into advanced age, with declines in medial temporal white matter mediating the negative effect of age on episodic memory performance. Chapter 2 used more advanced multicompartment diffusion imaging to assess relations between white matter microstructure and associative learning performance within a subset of 22 oldest-old adults from Chapter 1. Results indicated preserved associative learning abilities into the 10th decade of life that were supported by better microstructure of white matter connections between the prefrontal cortex and dorsal striatum. Findings from Chapters 1 and 2 were independent of diagnoses of cognitive impairment no dementia in oldest-old adults, suggesting that they were not driven by advanced age-related cognitive dysfunction. Finally, Chapter 3 examined whether these findings align with those from other MRI studies of oldest-old adults as well as predictions of select neurocognitive aging theories. Despite there being some continuity acr

Disease burden increases with age. Cancer and dementia are two age-related chronic diseases that most commonly occur in older adults. They are also amongst the top 10 leading causes of death and disability in this age group. Despite the increased risk of comorbidity at older ages, it is unlikely for cancer and dementia to present in the same person at the same time. Surprisingly, evidence suggests that rates of dementia are lower in older adults with a history of cancer and vice versa. However, whether this pattern of inverse association holds true for the oldest-old, remains unclear. The oldest-old represent the fastest growing age group of the world’s population yet have occupied only a small percentage of the population included in the published literature. The objective of this dissertation is to examine the relationship between cancer and dementia in the oldest-old using data from the 90+ Study at the University of California, Irvine. An initial cross-sectional study was performed as a preliminary analysis using data from the 90+ study. A logistic regression model of 1525 oldest-old participants with a) no history of cancer or b) a history of cancer, were assessed for having dementia at baseline enrollment into the 90+ study. Results showed a 36% reduced odds of dementia in participants with a prior history of cancer at baseline. Building off these preliminary analyses, two studies were performed to further evaluate the overall research question about the relationship between cancer and dementia in the oldest-old. Both research questions utilized data from the 90+ study. Specifically, the study population consisted of 761 older adults who were dementia free at baseline enrollment into the 90+ Study between 2003 to 2018.The first research objective was to measure the risk of dementia in the oldest-old with a prior history of cancer compared to the oldest-old who remained cancer free. Using cox proportional hazards we estimated the cause-specific hazard ratio to

Advanced old age has been characterized as a biologically highly vulnerable life phase. Biological, morbidity-, and cognitive impairment-related factors play an important role as mortality predictors among very old adults. However, it is largely unknown whether previous findings confirming the role of different wellbeing domains for mortality translate to survival among the oldest-old individuals. Moreover, the distinction established in the wellbeing literature between hedonic and eudaimonic wellbeing as well as the consideration of within-person variability of potentially relevant mortality predictors has not sufficiently been addressed in prior mortality research. In this study, we examined a broad set of hedonic and eudaimonic wellbeing indicators, including their levels, their changes, as well as their within-person variability, as predictors of all-cause mortality in a sample of very old individuals. We used data from the LateLine study, a 7-year longitudinal study based on a sample of n = 124 individuals who were living alone and who were aged 87–97 years (M = 90.6, SD = 2.9) at baseline. Study participants provided up to 16 measurement occasions (mean number of measurement occasions per individual = 5.50, SD = 4.79) between 2009 and 2016. Dates of death were available for 118 individuals (95.2%) who had deceased between 2009 and 2021. We ran longitudinal multilevel structural equation models and specified between-person level differences, within-person long-term linear change trends, as well as the “detrended” within-person variability in three indicators of hedonic (i.e., life satisfaction and positive and negative affect) and four indicators of eudaimonic wellbeing (i.e., purpose in life, autonomy, environmental mastery, and self-acceptance) as all-cause mortality predictors. Controlling for age, gender, education, and physical condition and testing our sets of hedonic and eudaimonic indictors separately in terms of their mortality impact, solely one eudai, Peer Reviewed

Purpose of reviewThe fastest-growing group of elderly individuals is the "oldest-old," usually defined as those age 85 years and above. These individuals account for much of the rapid increase in cases of dementing illness throughout the world but remain underrepresented in the body of literature on this topic. The aim of this review is first to outline the unique contributing factors and complications that must be considered by clinicians in evaluating an oldest-old individual with cognitive complaints. Secondly, the evidence for management of these cognitive concerns is reviewed.Recent findingsIn addition to well-established associations between impaired cognition and physical disability, falls, and frailty, there is now evidence that exercise performed decades earlier confers a cognitive benefit in the oldest-old. Moreover, though aggressive blood pressure control is critical earlier in life for prevention of strokes, renal disease, and other comorbidities, hypertension started after age 80 is in fact associated with a decreased risk of clinical dementia, carrying significant implications for the medical management of oldest-old individuals. The oldest-old are more likely to reside in care facilities, where social isolation might be exacerbated by a consistently lower rate of internet-connected device use. The COVID-19 pandemic has not only highlighted the increased mortality rate among the oldest-old but has also brought the increased social isolation in this group to the forte.SummaryDiffering from the "younger-old" in a number of respects, the oldest-old is a unique population not just in their vulnerability to cognitive disorders but also in the diagnostic challenges they can pose. The oldest-old are more likely to be afflicted by sensory deficits, physical disability, poor nutrition, frailty, and depression, which must be accounted for in the assessment of cognitive complaints as they may confound or complicate the presentation. Social isolation and ins

While aging is typically associated with cognitive decline, some individuals are able to diverge from the characteristic downward slope and maintain very high levels of cognitive performance. Prior studies have found that cortical thickness in the cingulate cortex, a region involved in information processing, memory, and attention, distinguish those with exceptional cognitive abilities when compared to their cognitively more typical elderly peers. Others major areas outside of the cingulate, such as the prefrontal cortex and insula, are also key in successful aging well into late age, suggesting that structural properties across a wide range of areas may better explain differences in cognitive abilities. Here, we aim to assess the role of regional cortical thickness, both in the cingulate and the whole brain, in modeling Top Cognitive Performance (TCP), measured by performance in the top 50th percentile of memory and executive function. Using data from National Alzheimer's Coordinating Center and The 90 + Study, we examined healthy subjects aged 70-100 years old. We found that, while thickness in cingulate regions can model TCP status with some degree of accuracy, a whole-brain, network-level approach out-performed the localist, cingulate models. These findings suggests a need for more network-style approaches and furthers our understanding of neurobiological factors contributing to preserved cognition.

BackgroundCognitive screening is important for the oldest-old (age 90 +). This age group is the fastest growing and has the highest risk of dementia. However, norms and score equivalence for screening tests are lacking for this group.AimsTo provide norms and score equivalence for commonly used cognitive screening tests for the oldest-old.MethodsData on 157 participants of the Center for Healthy Aging Longevity Study aged 90 + were analyzed. First, we derived norms for (1) subtests and cognitive domains of the in-person Montreal Cognitive Assessment having a maximum score of 30 (MoCA-30) and (2) the total MoCA-22 score, obtained from the in-person MoCA-30 by summing the subtests that do not require visual input to a maximum score of 22. These norms were derived from 124 participants with a Mini-Mental State Examination (MMSE) ≥ 27. Second, we derived score equivalences for MMSE to MoCA-30 and MoCA-22, and MoCA-30 to MoCA-22 using equipercentile equating method with log-linear smoothing, based on all 157 participants.ResultsMoCA-22 total score norms are: mean = 18.3(standard deviation = 2.2). An MMSE score of 27 is equivalent to a MoCA-30 score of 22 and a MoCA-22 score of 16.Discussion and conclusionsSubtest, domain and MoCA-22 norms will aid in evaluation of the oldest-old who cannot complete the MoCA-30 or are tested over the phone. The equivalences of the three cognitive tests (MMSE, MoCA-30, MoCA-22) in the oldest-old will facilitate continuity of cognitive tracking of individuals tested with different tests over time and comparison of the studies that use different cognitive tests.

Objectives: Determinants of cognitive functioning in individuals aged 90 years and older, the oldest-old, remain poorly understood. We aimed to establish the association of risk factors, white matter hyperintensities (WMHs), hippocampal atrophy, and amyloid aggregation with cognition in the oldest-old. Method: We included 84 individuals without cognitive impairment and 38 individuals with cognitive impairment from the EMIF-AD 90+ Study (mean age 92.4 years) and tested cross-sectional associations between risk factors (cognitive activity, physical parameters, nutritional status, inflammatory markers, and cardiovascular risk factors), brain pathology biomarkers (WMH and hippocampal volume on magnetic resonance imaging, and amyloid binding measured with positron emission tomography), and cognition. Additionally, we tested whether the brain pathology biomarkers were independently associated with cognition. When applicable, we tested whether the effect of risk factors on cognition was mediated by brain pathology. Results: Lower values for handgrip strength, Short Physical Performance Battery (SPPB), nutritional status, HbA1c, and hippocampal volume, and higher values for WMH volume and amyloid binding were associated with worse cognition. Higher past cognitive activity and lower body mass index were associated with increased amyloid binding, lower muscle mass with more WMH, and lower SPPB scores with more WMH and hippocampal atrophy. The brain pathology markers were independently associated with cognition. The association of SPPB with cognition was partially mediated by hippocampal volume. Discussion: In the oldest-old, physical parameters, nutritional status, HbA1c, WMH, hippocampal atrophy, and amyloid binding are associated with cognitive impairment. Physical performance may affect cognition through hippocampal atrophy. This study highlights the importance to consider multiple factors when assessing cognition in the oldest-old.

Older adults 75 and above are a fast-growing segment of the population. However, few studies have investigated what it means to age successfully from their perspective. This group of older adults face challenges that might characteristically differ from younger older adults. Therefore, the aim of this study was to conduct a systematic review of the perspectives of older adults aged 75 and above regarding what it means to age successfully and to summarise the findings through a narrative synthesis. We also aimed to provide a snapshot of inhibitors and facilitators to achieve successful ageing. A systematic review of the 75+ older adults’ perspectives was conducted across PubMed, CINAHL, Scopus, Web of Science and PsycINFO. Qualitative, quantitative and mixed-methods original peer-reviewed studies were included. After reviewing 4,661 articles, 15 articles met the inclusion criteria and 15 themes were identified. They ranged from biomedical components such as physical functioning to psychosocial components such as relationships, reflections on life and past experiences, preparations for death and environmental factors. The findings revealed that as people age, their definition of successful ageing changes, expanding the current conceptualisation of successful ageing by including additional factors that can act as facilitators and/or inhibitors, such as death and environmental factors. The findings also highlight the need for further research on theory development by considering age-related differences and the perspectives of under-studied populations.

Purpose of reviewThe fastest-growing group of elderly individuals is the "oldest-old," usually defined as those age 85 years and above. These individuals account for much of the rapid increase in cases of dementing illness throughout the world but remain underrepresented in the body of literature on this topic. The aim of this review is first to outline the unique contributing factors and complications that must be considered by clinicians in evaluating an oldest-old individual with cognitive complaints. Secondly, the evidence for management of these cognitive concerns is reviewed.Recent findingsIn addition to well-established associations between impaired cognition and physical disability, falls, and frailty, there is now evidence that exercise performed decades earlier confers a cognitive benefit in the oldest-old. Moreover, though aggressive blood pressure control is critical earlier in life for prevention of strokes, renal disease, and other comorbidities, hypertension started after age 80 is in fact associated with a decreased risk of clinical dementia, carrying significant implications for the medical management of oldest-old individuals. The oldest-old are more likely to reside in care facilities, where social isolation might be exacerbated by a consistently lower rate of internet-connected device use. The COVID-19 pandemic has not only highlighted the increased mortality rate among the oldest-old but has also brought the increased social isolation in this group to the forte.SummaryDiffering from the "younger-old" in a number of respects, the oldest-old is a unique population not just in their vulnerability to cognitive disorders but also in the diagnostic challenges they can pose. The oldest-old are more likely to be afflicted by sensory deficits, physical disability, poor nutrition, frailty, and depression, which must be accounted for in the assessment of cognitive complaints as they may confound or complicate the presentation. Social isolation and ins

BackgroundCognitive screening is important for the oldest-old (age 90 +). This age group is the fastest growing and has the highest risk of dementia. However, norms and score equivalence for screening tests are lacking for this group.AimsTo provide norms and score equivalence for commonly used cognitive screening tests for the oldest-old.MethodsData on 157 participants of the Center for Healthy Aging Longevity Study aged 90 + were analyzed. First, we derived norms for (1) subtests and cognitive domains of the in-person Montreal Cognitive Assessment having a maximum score of 30 (MoCA-30) and (2) the total MoCA-22 score, obtained from the in-person MoCA-30 by summing the subtests that do not require visual input to a maximum score of 22. These norms were derived from 124 participants with a Mini-Mental State Examination (MMSE) ≥ 27. Second, we derived score equivalences for MMSE to MoCA-30 and MoCA-22, and MoCA-30 to MoCA-22 using equipercentile equating method with log-linear smoothing, based on all 157 participants.ResultsMoCA-22 total score norms are: mean = 18.3(standard deviation = 2.2). An MMSE score of 27 is equivalent to a MoCA-30 score of 22 and a MoCA-22 score of 16.Discussion and conclusionsSubtest, domain and MoCA-22 norms will aid in evaluation of the oldest-old who cannot complete the MoCA-30 or are tested over the phone. The equivalences of the three cognitive tests (MMSE, MoCA-30, MoCA-22) in the oldest-old will facilitate continuity of cognitive tracking of individuals tested with different tests over time and comparison of the studies that use different cognitive tests.

Purpose of reviewPeople over 90 are the fastest growing segment of the population with the highest rates of dementia. This review highlights recent findings that provide insight to our understanding of dementia and cognition at all ages.Recent findingsRisk factors for Alzheimer's disease (AD) and dementia differ by age, with some factors, like the development of hypertension, actually becoming protective in the oldest-old. At least half of all dementia in this age group is due to non AD pathologies, including microinfarcts, hippocampal sclerosis and TDP-43. The number of pathologic changes found in the brain is related to both risk and severity of dementia, but many people in this age group appear to be 'resilient' to these pathologies. Resilience to Alzheimer pathology, in part, may be related to absence of other pathologies, and imaging and spinal fluid biomarkers for AD have limited utility in this age group.SummaryStudies of dementia in the oldest-old are important for our understanding and eventual treatment or prevention of dementia at all ages.

While aging is typically associated with cognitive decline, some individuals are able to diverge from the characteristic downward slope and maintain very high levels of cognitive performance. Prior studies have found that cortical thickness in the cingulate cortex, a region involved in information processing, memory, and attention, distinguish those with exceptional cognitive abilities when compared to their cognitively more typical elderly peers. Others major areas outside of the cingulate, such as the prefrontal cortex and insula, are also key in successful aging well into late age, suggesting that structural properties across a wide range of areas may better explain differences in cognitive abilities. Here, we aim to assess the role of regional cortical thickness, both in the cingulate and the whole brain, in modeling Top Cognitive Performance (TCP), measured by performance in the top 50th percentile of memory and executive function. Using data from National Alzheimer's Coordinating Center and The 90 + Study, we examined healthy subjects aged 70-100 years old. We found that, while thickness in cingulate regions can model TCP status with some degree of accuracy, a whole-brain, network-level approach out-performed the localist, cingulate models. These findings suggests a need for more network-style approaches and furthers our understanding of neurobiological factors contributing to preserved cognition.

Background: Changes in older people’s symptoms across recent decades have not been investigated. Aims: We analyzed temporal trends in symptom burden by comparing data from independent, cross-sectional cohorts retrieved in 1989, 1999, 2009, and 2019. Furthermore, we compared the association between symptom burden and psychological wellbeing (PWB) in older men and women. Methods: The Helsinki Aging Study recruited a random sample of people aged 75, 80, and 85 in 1989, and random samples aged 75, 80, 85, 90, and 95 in 1999, 2009, and 2019 (four study waves). Altogether, 6263 community-dwelling people answered the questions concerning symptoms in the questionnaire surveys. The symptoms inquired in all study waves were dizziness, back pain, joint pain, chest pain, shortness of breath, and loss of appetite. Symptom burden was calculated according to the number of symptoms and their frequency (score range: 0–6). PWB and the Charlson comorbidity index were calculated. Results: Symptom burden decreased in both men and women aged 75 and 80 from 1989 to 2019. Changes in cohorts aged 85 + were nonsignificant. There was a significant difference in symptom burden between men and women in all ages with men having fewer symptoms. PWB decreased with increasing symptom burden. Men had greater PWB than women up to severe levels of symptom burden. Conclusions: Symptom burden decreased from 1989 to 2019 in cohorts aged 75–80, whereas changes remained nonsignificant in cohorts aged 85 +. To our knowledge, this is the first study to examine temporal trends in symptom burden.

Objectives: Determinants of cognitive functioning in individuals aged 90 years and older, the oldest-old, remain poorly understood. We aimed to establish the association of risk factors, white matter hyperintensities (WMHs), hippocampal atrophy, and amyloid aggregation with cognition in the oldest-old. Method: We included 84 individuals without cognitive impairment and 38 individuals with cognitive impairment from the EMIF-AD 90+ Study (mean age 92.4 years) and tested cross-sectional associations between risk factors (cognitive activity, physical parameters, nutritional status, inflammatory markers, and cardiovascular risk factors), brain pathology biomarkers (WMH and hippocampal volume on magnetic resonance imaging, and amyloid binding measured with positron emission tomography), and cognition. Additionally, we tested whether the brain pathology biomarkers were independently associated with cognition. When applicable, we tested whether the effect of risk factors on cognition was mediated by brain pathology. Results: Lower values for handgrip strength, Short Physical Performance Battery (SPPB), nutritional status, HbA1c, and hippocampal volume, and higher values for WMH volume and amyloid binding were associated with worse cognition. Higher past cognitive activity and lower body mass index were associated with increased amyloid binding, lower muscle mass with more WMH, and lower SPPB scores with more WMH and hippocampal atrophy. The brain pathology markers were independently associated with cognition. The association of SPPB with cognition was partially mediated by hippocampal volume. Discussion: In the oldest-old, physical parameters, nutritional status, HbA1c, WMH, hippocampal atrophy, and amyloid binding are associated with cognitive impairment. Physical performance may affect cognition through hippocampal atrophy. This study highlights the importance to consider multiple factors when assessing cognition in the oldest-old.

Objective: This study aimed to examine the relationship between sleep duration and all-cause mortality, and to assess the role of cognitive impairment, physical disability, and chronic conditions on this association among very old adults. Design: A prospective cohort study. Setting and Participants: Within the Chinese Longitudinal Healthy Longevity Surveys, 17,637 oldest-old aged 80-105 years were followed up to 10 years (2005- 2014). Measures: Data on sleep duration at baseline were based on self-report and were categorized as short (<7 hour), moderate (7-9 hours), and long sleep (>9 hours). Information on cognitive function using the Mini-Mental State Examination (MMSE), physical disability using Activities of Daily Living (ADL), and chronic conditions including diabetes, heart disease, stroke, asthma, and cancer were collected at baseline based on a structured questionnaire. Information about vital status was ascertained and confirmed by a close family member or village doctor of the participant during the follow-up. Data were analyzed using Cox proportional hazards models, with adjustment for potential confounders. Results: During the follow-up of 10 years, 11,067 (62.7%) participants died. The multivariate-adjusted hazard ratios (HRs) with 95% confidence interval (CI) for mortality were 1.03 (0.98-1.09) for short sleep and 1.13 (1.08-1.18) for long sleep compared with moderate sleep duration. In stratified analysis by cognitive impairment, physical disability, and chronic conditions, the risk of morality was present only among people with MMSE scores <= 24 but did not differ much when stratified by physical disability and chronic conditions. There was a statistically significant interaction between long sleep and cognitive impairment on mortality (P for interaction = .002). Conclusions and Implications: Long sleep duration is associated with higher risk of mortality in very old adults independently of health conditions. Cognitive impairment may enhance

Objective: This study aimed to investigate the association of endogenous and exogenous estrogen exposure with risk of incident dementia in the oldest-old (age 90+ years).Methods: Participants were part of The 90+ Study, a longitudinal study begun in 2003 of aging and dementia among people aged 90+ years. Menstrual, reproductive, and menopausal data were collected in the 1980s as part of the population-based Leisure World Cohort Study. Cognitive status at baseline was determined from an in-person neurological evaluation with biannual follow-up through June 2019. Hazard ratios (HRs) of dementia associated with estrogen-related variables were estimated using Cox regression analysis. No adjustment was made for multiple comparisons.Results: A total of 424 women without dementia at baseline had at least one follow-up evaluation. The mean age was 68.5 years at enrollment in the Leisure World Cohort Study, 93.2 years at enrollment in The 90+ Study, and 96.5 years at last follow-up. During follow-up (mean 3.4 years) dementia was diagnosed in 209 (49%) participants. No individual menstrual, reproductive, menopausal, or estrogen replacement variable was associated with risk of incident dementia after age 90 years. However, women with a high endogenous estrogen exposure index (summarizing exposure from menarche to menopause) had a non-significant 25% lower risk (HR = 0.75, 95% confidence interval 0.53-1.06).Conclusions: Prior exposure to estrogen, endogenous or exogenous, had little effect on risk of dementia in the 10th decade of life.

Background Very few population-based studies have investigated self-rated health and related factors in the increasing age group 85 years or older. The aim of this study was to examine self-rated health and its association with living conditions, lifestyle factors, physical and mental health problems and functional ability among the oldest-old in the general population in Sweden. Methods The study is cross-sectional and based on 1360 persons, 85 years of age or older, who answered a survey questionnaire sent to a random population sample in 2012 (participation rate 47%). Multivariate logistic regression was used as the statistical method. Results The prevalence of good self-rated health was 39% in men and 30% in women. Physical inactivity, impaired physical mobility, pain, anxiety/depression and longstanding illness were independently associated with poorer than good self-rated health, while factors such as gender, age, educational level, cash margin, living alone, social support, smoking, alcohol use, obesity, accidents and impaired vision/hearing were not. Conclusions While a considerable part of the oldest-old assess their health as good, not being physically active and having common health problems such as pain and depression as well as impaired physical mobility are associated with poorer than good self-rated health. This should be considered when planning how to improve and maintain health in the growing population of persons 85 years and older.

Background Very few population-based studies have investigated self-rated health and related factors in the increasing age group 85 years or older. The aim of this study was to examine self-rated health and its association with living conditions, lifestyle factors, physical and mental health problems and functional ability among the oldest-old in the general population in Sweden. Methods The study is cross-sectional and based on 1360 persons, 85 years of age or older, who answered a survey questionnaire sent to a random population sample in 2012 (participation rate 47%). Multivariate logistic regression was used as the statistical method. Results The prevalence of good self-rated health was 39% in men and 30% in women. Physical inactivity, impaired physical mobility, pain, anxiety/depression and longstanding illness were independently associated with poorer than good self-rated health, while factors such as gender, age, educational level, cash margin, living alone, social support, smoking, alcohol use, obesity, accidents and impaired vision/hearing were not. Conclusions While a considerable part of the oldest-old assess their health as good, not being physically active and having common health problems such as pain and depression as well as impaired physical mobility are associated with poorer than good self-rated health. This should be considered when planning how to improve and maintain health in the growing population of persons 85 years and older.

Objective: This study aimed to investigate the association of endogenous and exogenous estrogen exposure with risk of incident dementia in the oldest-old (age 90+ years).Methods: Participants were part of The 90+ Study, a longitudinal study begun in 2003 of aging and dementia among people aged 90+ years. Menstrual, reproductive, and menopausal data were collected in the 1980s as part of the population-based Leisure World Cohort Study. Cognitive status at baseline was determined from an in-person neurological evaluation with biannual follow-up through June 2019. Hazard ratios (HRs) of dementia associated with estrogen-related variables were estimated using Cox regression analysis. No adjustment was made for multiple comparisons.Results: A total of 424 women without dementia at baseline had at least one follow-up evaluation. The mean age was 68.5 years at enrollment in the Leisure World Cohort Study, 93.2 years at enrollment in The 90+ Study, and 96.5 years at last follow-up. During follow-up (mean 3.4 years) dementia was diagnosed in 209 (49%) participants. No individual menstrual, reproductive, menopausal, or estrogen replacement variable was associated with risk of incident dementia after age 90 years. However, women with a high endogenous estrogen exposure index (summarizing exposure from menarche to menopause) had a non-significant 25% lower risk (HR = 0.75, 95% confidence interval 0.53-1.06).Conclusions: Prior exposure to estrogen, endogenous or exogenous, had little effect on risk of dementia in the 10th decade of life.

Background: Health, as defined by the WHO, is a multidimensional concept that includes different aspects. Interest in the health conditions of the oldest-old has increased as a consequence of the phenomenon of population aging. This study investigates whether (1) it is possible to identify health profiles among the oldest-old, taking into account physical, emotional and psychological information about health, and (2) there are demographic and socioeconomic differences among the health profiles. Methods: Latent Class Analysis with covariates was applied to the Mugello Study data to identify health profiles among the 504 nonagenarians residing in the Mugello district (Tuscany, Italy) and to evaluate the association between socioeconomic characteristics and the health profiles resulting from the analysis. Results: This study highlights four groups labeled according to the posterior probability of determining a certain health characteristic: "healthy", "physically healthy with cognitive impairment", "unhealthy", and "severely unhealthy". Some demographic and socioeconomic characteristics were found to be associated with the final groups: older nonagenarians are more likely to be in worse health conditions; men are in general healthier than women; more educated individuals are less likely to be in extremely poor health conditions, while the lowest-educated are more likely to be cognitively impaired; and office or intellectual workers are less likely to be in poor health conditions than are farmers. Conclusions: Considering multiple dimensions of health to determine health profiles among the oldest-old could help to better evaluate their care needs according to their health status.

Background Very few population-based studies have investigated self-rated health and related factors in the increasing age group 85 years or older. The aim of this study was to examine self-rated health and its association with living conditions, lifestyle factors, physical and mental health problems and functional ability among the oldest-old in the general population in Sweden. Methods The study is cross-sectional and based on 1360 persons, 85 years of age or older, who answered a survey questionnaire sent to a random population sample in 2012 (participation rate 47%). Multivariate logistic regression was used as the statistical method. Results The prevalence of good self-rated health was 39% in men and 30% in women. Physical inactivity, impaired physical mobility, pain, anxiety/depression and longstanding illness were independently associated with poorer than good self-rated health, while factors such as gender, age, educational level, cash margin, living alone, social support, smoking, alcohol use, obesity, accidents and impaired vision/hearing were not. Conclusions While a considerable part of the oldest-old assess their health as good, not being physically active and having common health problems such as pain and depression as well as impaired physical mobility are associated with poorer than good self-rated health. This should be considered when planning how to improve and maintain health in the growing population of persons 85 years and older.

Background Very few population-based studies have investigated self-rated health and related factors in the increasing age group 85 years or older. The aim of this study was to examine self-rated health and its association with living conditions, lifestyle factors, physical and mental health problems and functional ability among the oldest-old in the general population in Sweden. Methods The study is cross-sectional and based on 1360 persons, 85 years of age or older, who answered a survey questionnaire sent to a random population sample in 2012 (participation rate 47%). Multivariate logistic regression was used as the statistical method. Results The prevalence of good self-rated health was 39% in men and 30% in women. Physical inactivity, impaired physical mobility, pain, anxiety/depression and longstanding illness were independently associated with poorer than good self-rated health, while factors such as gender, age, educational level, cash margin, living alone, social support, smoking, alcohol use, obesity, accidents and impaired vision/hearing were not. Conclusions While a considerable part of the oldest-old assess their health as good, not being physically active and having common health problems such as pain and depression as well as impaired physical mobility are associated with poorer than good self-rated health. This should be considered when planning how to improve and maintain health in the growing population of persons 85 years and older.

Background Very few population-based studies have investigated self-rated health and related factors in the increasing age group 85 years or older. The aim of this study was to examine self-rated health and its association with living conditions, lifestyle factors, physical and mental health problems and functional ability among the oldest-old in the general population in Sweden. Methods The study is cross-sectional and based on 1360 persons, 85 years of age or older, who answered a survey questionnaire sent to a random population sample in 2012 (participation rate 47%). Multivariate logistic regression was used as the statistical method. Results The prevalence of good self-rated health was 39% in men and 30% in women. Physical inactivity, impaired physical mobility, pain, anxiety/depression and longstanding illness were independently associated with poorer than good self-rated health, while factors such as gender, age, educational level, cash margin, living alone, social support, smoking, alcohol use, obesity, accidents and impaired vision/hearing were not. Conclusions While a considerable part of the oldest-old assess their health as good, not being physically active and having common health problems such as pain and depression as well as impaired physical mobility are associated with poorer than good self-rated health. This should be considered when planning how to improve and maintain health in the growing population of persons 85 years and older.

Objective: This study aimed to investigate the association of endogenous and exogenous estrogen exposure with risk of incident dementia in the oldest-old (age 90+ years).Methods: Participants were part of The 90+ Study, a longitudinal study begun in 2003 of aging and dementia among people aged 90+ years. Menstrual, reproductive, and menopausal data were collected in the 1980s as part of the population-based Leisure World Cohort Study. Cognitive status at baseline was determined from an in-person neurological evaluation with biannual follow-up through June 2019. Hazard ratios (HRs) of dementia associated with estrogen-related variables were estimated using Cox regression analysis. No adjustment was made for multiple comparisons.Results: A total of 424 women without dementia at baseline had at least one follow-up evaluation. The mean age was 68.5 years at enrollment in the Leisure World Cohort Study, 93.2 years at enrollment in The 90+ Study, and 96.5 years at last follow-up. During follow-up (mean 3.4 years) dementia was diagnosed in 209 (49%) participants. No individual menstrual, reproductive, menopausal, or estrogen replacement variable was associated with risk of incident dementia after age 90 years. However, women with a high endogenous estrogen exposure index (summarizing exposure from menarche to menopause) had a non-significant 25% lower risk (HR = 0.75, 95% confidence interval 0.53-1.06).Conclusions: Prior exposure to estrogen, endogenous or exogenous, had little effect on risk of dementia in the 10th decade of life.

ObjectivesTo study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old.DesignOngoing longitudinal study.SettingIn Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017.ParticipantsIndividuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment).MeasurementsCognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education.ResultsMean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline.ConclusionWe show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults

IntroductionLittle is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence.MethodsIncident dementia diagnoses from 1/1/2010 to 9/30/2015 were abstracted from medical records for 2350 members of an integrated health care system in California (n = 1702 whites, n = 375 blacks, n = 105 Latinos, n = 168 Asians) aged ≥90 in 2010. We estimated race/ethnicity-specific age-adjusted dementia incidence rates and implemented Cox proportional hazards models and Fine and Gray competing risk of death models adjusted for demographics and comorbidities in midlife and late-life.ResultsDementia incidence rates (n = 771 cases) were lowest among Asians (89.9/1000 person-years), followed by whites (96.9/1000 person-years), Latinos (105.8/1000 person-years), and blacks (121.5/1000 person-years). Cox regression and competing risk models estimated 28% and 36% higher dementia risk for blacks versus whites adjusting for demographics and comorbidities.DiscussionPatterns of racial/ethnic disparities in dementia seen in younger older adults continue after the age of 90 years, though smaller in magnitude.

BACKGROUND China has transitioned from being one of the fastest-growing populations to among the most rapidly aging countries worldwide. In particular, the population of oldest-old individuals, those aged 80+, is projected to quadruple by 2050. The oldest-old represent a uniquely important group-they have high demand for personal assistance and the highest healthcare costs of any age group. Understanding trends in disability and longevity among the oldest-old-that is, whether successive generations are living longer and with less disability-is of great importance for policy and planning purposes. METHODS We utilized data from successive birth cohorts (n = 20,520) of the Chinese oldest-old born 10 years apart (the earlier cohort was interviewed in 1998 and the later cohort in 2008). Disability was defined as needing personal assistance in performing one or more of five essential activities (bathing, transferring, dressing, eating, and toileting) or being incontinent. Participants were followed for age-specific disability transitions and mortality (in 2000 and 2002 for the earlier cohort and 2011 and 2014 for the later cohort), which were then used to generate microsimulation-based multistate life tables to estimate partial life expectancy (LE) and disability-free LE (DFLE), stratified by sex and age groups (octogenarians, nonagenarians, and centenarians). We additionally explored sociodemographic heterogeneity in LE and DFLE by urban/rural residence and educational attainment. RESULTS More recently born Chinese octogenarians (born 1919-1928) had a longer partial LE between ages 80 and 89 than octogenarians born 1909-1918, and octogenarian women experienced an increase in partial DFLE of 0.32 years (P = 0.004) across the two birth cohorts. Although no increases in partial LE were observed among nonagenarians or centenarians, partial DFLE increased across birth cohorts, with a gain of 0.41 years (P < 0.001) among nonagenarians and 0.07 years (P = 0.050) among centenari

ObjectivesTo study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old.DesignOngoing longitudinal study.SettingIn Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017.ParticipantsIndividuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment).MeasurementsCognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education.ResultsMean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline.ConclusionWe show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults

IntroductionLittle is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence.MethodsIncident dementia diagnoses from 1/1/2010 to 9/30/2015 were abstracted from medical records for 2350 members of an integrated health care system in California (n = 1702 whites, n = 375 blacks, n = 105 Latinos, n = 168 Asians) aged ≥90 in 2010. We estimated race/ethnicity-specific age-adjusted dementia incidence rates and implemented Cox proportional hazards models and Fine and Gray competing risk of death models adjusted for demographics and comorbidities in midlife and late-life.ResultsDementia incidence rates (n = 771 cases) were lowest among Asians (89.9/1000 person-years), followed by whites (96.9/1000 person-years), Latinos (105.8/1000 person-years), and blacks (121.5/1000 person-years). Cox regression and competing risk models estimated 28% and 36% higher dementia risk for blacks versus whites adjusting for demographics and comorbidities.DiscussionPatterns of racial/ethnic disparities in dementia seen in younger older adults continue after the age of 90 years, though smaller in magnitude.

OBJECTIVES: To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old. DESIGN: Ongoing longitudinal study. SETTING: In Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017. PARTICIPANTS: Individuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment). MEASUREMENTS: Cognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education. RESULTS: Mean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline. CONCLUSION: We show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger g

INTRODUCTION: Little is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence. METHODS: Incident dementia diagnoses from 1/1/2010 to 9/30/2015 were abstracted from medical records for 2350 members of an integrated health care system in California (n = 1702 whites, n = 375 blacks, n = 105 Latinos, n = 168 Asians) aged ≥90 in 2010. We estimated race/ethnicity-specific age-adjusted dementia incidence rates and implemented Cox proportional hazards models and Fine and Gray competing risk of death models adjusted for demographics and comorbidities in midlife and late-life. RESULTS: Dementia incidence rates (n = 771 cases) were lowest among Asians (89.9/1000 person-years), followed by whites (96.9/1000 person-years), Latinos (105.8/1000 person-years), and blacks (121.5/1000 person-years). Cox regression and competing risk models estimated 28% and 36% higher dementia risk for blacks versus whites adjusting for demographics and comorbidities. DISCUSSION: Patterns of racial/ethnic disparities in dementia seen in younger older adults continue after the age of 90 years, though smaller in magnitude.

BackgroundSeveral lines of research support associations between sleep and cognition in older adults. However, there is a paucity of data regarding sleep and cognition in nonagenarians and centenarians.AimsThe current study examined self-reported sleep quantity and sleep quality in relation to hippocampal volume and cognition in adults aged 90 and older.MethodsA total of 144 participants of The 90+ Study completed The Medical Outcomes Study sleep questionnaire. Participants reported subjective sleep duration in hours and three sleep quality factors: sleep problems, adequacy, and somnolence. Neuropsychological assessments of memory, global cognition, language, and executive function were completed, on average, 61 days from the questionnaire. Hippocampal volume on 3 T MRI, adjusted for intracranial volume, was obtained in 82 participants. We performed multiple linear regressions, controlling for age, sex, education, sleep medication, and depression, to examine sleep characteristics in relation to hippocampal volume and cognitive performance in all the subjects and then stratified by cognition.ResultsSleep duration > 8 h was associated with lower scores in tests of global cognition, memory, and executive function compared to sleep duration of 7-8 h when collapsing across cognitive status, but only with memory in cognitively impaired subjects, and not in cognitively normal subjects.Conclusions and discussionLong-sleep duration is associated with poorer global cognition, memory, and executive function in the oldest-old, and is only associated with memory in cognitively impaired oldest-old. Additional research is necessary to determine if sleep duration is a risk factor or a result of poor cognition in advanced age.

BackgroundSeveral lines of research support associations between sleep and cognition in older adults. However, there is a paucity of data regarding sleep and cognition in nonagenarians and centenarians.AimsThe current study examined self-reported sleep quantity and sleep quality in relation to hippocampal volume and cognition in adults aged 90 and older.MethodsA total of 144 participants of The 90+ Study completed The Medical Outcomes Study sleep questionnaire. Participants reported subjective sleep duration in hours and three sleep quality factors: sleep problems, adequacy, and somnolence. Neuropsychological assessments of memory, global cognition, language, and executive function were completed, on average, 61 days from the questionnaire. Hippocampal volume on 3 T MRI, adjusted for intracranial volume, was obtained in 82 participants. We performed multiple linear regressions, controlling for age, sex, education, sleep medication, and depression, to examine sleep characteristics in relation to hippocampal volume and cognitive performance in all the subjects and then stratified by cognition.ResultsSleep duration > 8 h was associated with lower scores in tests of global cognition, memory, and executive function compared to sleep duration of 7-8 h when collapsing across cognitive status, but only with memory in cognitively impaired subjects, and not in cognitively normal subjects.Conclusions and discussionLong-sleep duration is associated with poorer global cognition, memory, and executive function in the oldest-old, and is only associated with memory in cognitively impaired oldest-old. Additional research is necessary to determine if sleep duration is a risk factor or a result of poor cognition in advanced age.

Objectives: We previously found large variations in general practitioner (GP) hypertension treatment probability in oldest-old (>80 years) between countries. We wanted to explore whether differences in country-specific cardiovascular disease (CVD) burden and life expectancy could explain the differences. Design: This is a survey study using case-vignettes of oldest-old patients with different comorbidities and blood pressure levels. An ecological multilevel model analysis was performed. Setting: GP respondents from European General Practice Research Network (EGPRN) countries, Brazil and New Zeeland. Subjects: This study included 2543 GPs from 29 countries. Main outcome measures: GP treatment probability to start or not start antihypertensive treatment based on responses to case-vignettes; either low (<50% started treatment) or high (!50% started treatment). CVD burden is defined as ratio of disability-adjusted life years (DALYs) lost due to ischemic heart disease and/or stroke and total DALYs lost per country; life expectancy at age 60 and prevalence of oldest-old per country. Results: Of 1947 GPs (76%) responding to all vignettes, 787 (40%) scored high treatment probability and 1160 (60%) scored low. GPs in high CVD burden countries had higher odds of treatment probability (OR 3.70; 95% confidence interval (CI) 3.00–4.57); in countries with low life expectancy at 60, CVD was associated with high treatment probability (OR 2.18, 95% CI 1.12–4.25); but not in countries with high life expectancy (OR 1.06, 95% CI 0.56–1.98). Conclusions: GPs’ choice to treat/not treat hypertension in oldest-old was explained by differences in country-specific health characteristics. GPs in countries with high CVD

Objectives: We previously found large variations in general practitioner (GP) hypertension treatment probability in oldest-old (>80 years) between countries. We wanted to explore whether differences in country-specific cardiovascular disease (CVD) burden and life expectancy could explain the differences. Design: This is a survey study using case-vignettes of oldest-old patients with different comorbidities and blood pressure levels. An ecological multilevel model analysis was performed. Setting: GP respondents from European General Practice Research Network (EGPRN) countries, Brazil and New Zeeland. Subjects: This study included 2543 GPs from 29 countries. Main outcome measures: GP treatment probability to start or not start antihypertensive treatment based on responses to case-vignettes; either low (<50% started treatment) or high (!50% started treatment). CVD burden is defined as ratio of disability-adjusted life years (DALYs) lost due to ischemic heart disease and/or stroke and total DALYs lost per country; life expectancy at age 60 and prevalence of oldest-old per country. Results: Of 1947 GPs (76%) responding to all vignettes, 787 (40%) scored high treatment probability and 1160 (60%) scored low. GPs in high CVD burden countries had higher odds of treatment probability (OR 3.70; 95% confidence interval (CI) 3.00–4.57); in countries with low life expectancy at 60, CVD was associated with high treatment probability (OR 2.18, 95% CI 1.12–4.25); but not in countries with high life expectancy (OR 1.06, 95% CI 0.56–1.98). Conclusions: GPs’ choice to treat/not treat hypertension in oldest-old was explained by differences in country-specific health characteristics. GPs in countries with high CVD

BACKGROUND: Several lines of research support associations between sleep and cognition in older adults. However, there is a paucity of data regarding sleep and cognition in nonagenarians and centenarians. AIMS: The current study examined self-reported sleep quantity and sleep quality in relation to hippocampal volume and cognition in adults aged 90 and older. METHODS: A total of 144 participants of The 90+ Study completed The Medical Outcomes Study sleep questionnaire. Participants reported subjective sleep duration in hours and three sleep quality factors: sleep problems, adequacy, and somnolence. Neuropsychological assessments of memory, global cognition, language, and executive function were completed, on average, 61 days from the questionnaire. Hippocampal volume on 3 T MRI, adjusted for intracranial volume, was obtained in 82 participants. We performed multiple linear regressions, controlling for age, sex, education, sleep medication, and depression, to examine sleep characteristics in relation to hippocampal volume and cognitive performance in all the subjects and then stratified by cognition. RESULTS: Sleep duration > 8 h was associated with lower scores in tests of global cognition, memory, and executive function compared to sleep duration of 7-8 h when collapsing across cognitive status, but only with memory in cognitively impaired subjects, and not in cognitively normal subjects. CONCLUSIONS AND DISCUSSION: Long-sleep duration is associated with poorer global cognition, memory, and executive function in the oldest-old, and is only associated with memory in cognitively impaired oldest-old. Additional research is necessary to determine if sleep duration is a risk factor or a result of poor cognition in advanced age.

OBJECTIVES: We previously found large variations in general practitioner (GP) hypertension treatment probability in oldest-old (>80 years) between countries. We wanted to explore whether differences in country-specific cardiovascular disease (CVD) burden and life expectancy could explain the differences. DESIGN: This is a survey study using case-vignettes of oldest-old patients with different comorbidities and blood pressure levels. An ecological multilevel model analysis was performed. SETTING: GP respondents from European General Practice Research Network (EGPRN) countries, Brazil and New Zeeland. SUBJECTS: This study included 2543 GPs from 29 countries. MAIN OUTCOME MEASURES: GP treatment probability to start or not start antihypertensive treatment based on responses to case-vignettes; either low (<50% started treatment) or high (≥50% started treatment). CVD burden is defined as ratio of disability-adjusted life years (DALYs) lost due to ischemic heart disease and/or stroke and total DALYs lost per country; life expectancy at age 60 and prevalence of oldest-old per country. RESULTS: Of 1947 GPs (76%) responding to all vignettes, 787 (40%) scored high treatment probability and 1160 (60%) scored low. GPs in high CVD burden countries had higher odds of treatment probability (OR 3.70; 95% confidence interval (CI) 3.00-4.57); in countries with low life expectancy at 60, CVD was associated with high treatment probability (OR 2.18, 95% CI 1.12-4.25); but not in countries with high life expectancy (OR 1.06, 95% CI 0.56-1.98). CONCLUSIONS: GPs' choice to treat/not treat hypertension in oldest-old was explained by differences in country-specific health characteristics. GPs in countries with high CVD burden and low life expectancy at age 60 were most likely to treat hypertension in oldest-old. Key Points • General practitioners (GPs) are in a clinical dilemma when deciding whether (or not) to treat hypertension in the oldest-old (>80 years of age). • In this stud

Background The oldest-old (aged ≥85 years) are the fastest growing age group, with the highest risk of cognitive impairment and dementia. This study investigated whether cognitive reserve applies to the oldest-old. This has implications for cognitive interventions in this age group. Methods Baseline and 5-year follow-up data from the Newcastle 85+ Study were used (N = 845, mean age = 85.5, 38% male). A Cognitive Reserve Index (CRI) was created, including: education, social class, marital status, engagement in mental activities, social participation, and physical activity. Global (Mini-Mental State Examination) and domain specific (Cognitive Drug Research Battery subtests assessing memory, attention, and speed) cognitive functions were assessed. Dementia diagnosis was determined by health records. Logistic regression analysis examined the association between CRI scores and incident dementia. Mixed effects models investigated baseline and longitudinal associations between the CRI scores and cognitive function. Analyses controlled for sex, age, depression, and cardiovascular disease history. Results Higher reserve associated with better cognitive performance on all baseline measures, but not 5-year rate of change. The CRI associated with prevalent, but not incident dementia. Conclusions In the oldest-old, higher reserve associated with better baseline global and domain-specific cognitive function and reduced risk of prevalent dementia; but not cognitive decline or incident dementia. Increasing reserve could promote cognitive function in the oldest-old. The results suggest there would be little impact on trajectories, but replication is needed. Development of preventative strategies would benefit from identifying the role of each factor in building reserve and why rate of change is not affected.

Chronic health conditions are commonplace in older populations. The process of aging impacts many of the world's top health concerns. With the average life expectancy continuing to climb, understanding patterns of morbidity in aging populations has become progressively more important. Cancer is an age-related disease, whose risk has been proven to increase with age. Limited information is published about the epidemiology of cancer and the cancer contribution to mortality in the 85+ age group, often referred to as the oldest-old. In this review, we perform a comprehensive assessment of the most recent (2011-2016) literature on cancer prevalence, incidence and mortality in the oldest-old. The data shows cancer prevalence and cancer incidence increases until ages 85-89, after which the rates decrease into 100+ ages. However the number of overall cases has steadily increased over time due to the rise in population. Cancer mortality continues to increase after age 85+. This review presents an overview of plausible associations between comorbidity, genetics and age-related physiological effects in relation to cancer risk and protection. Many of these age-related processes contribute to the lowered risk of cancer in the oldest-old, likewise other certain health conditions may "protect" from cancer in this age group.