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Open Access Publications from the University of California

Scholarly Works (13 results)

  • Article
  • Peer Reviewed
UC Irvine Previously Published Works (2012)
Population-based longitudinal clinicopathological studies provide an ideal opportunity to study a variety of risk and protective factors in relation to pathology associated with dementia in individuals who are representative of the general population. The 90+ Study is a population-based study designed specifically to study aging and dementia as well as its neuropathological correlates in participants 90 years of age and older. We present demographic and pathological data on the first 104 participants to come to autopsy from the brain donation component of the study, The 90+ Autopsy Study. Cognitive diagnosis was assigned according to diagnostic and statistical manual 4th edition criteria for dementia and neuropathological diagnoses were made according to the Consortium to Establish a Registry for Alzheimer's Disease protocol. Dementia was present in 61% of autopsied participants, the majority of whom were diagnosed with Alzheimer's disease (85%). Many different types of pathology typically associated with dementia were common in the oldest-old, and included neurofibrillary tangles, neuritic plaques, diffuse plaques, Lewy bodies, hippocampal sclerosis, and cerebral infarctions. Most types of pathology were more frequently found in participants suffering from dementia but there was extensive overlap in pathology among those with and without dementia. In addition, 22% of demented participants did not have sufficient pathology to account for their cognitive loss. Our results highlight the poor associations between these common pathological lesions and dementia in the oldest-old and the importance of considering many different types of pathology, possibly including some yet to be identified, in order to account for all dementias in the oldest-old.
    Cover page: A population-based clinicopathological study in the oldest-old: the 90+ study.Creative Commons 'BY' version 4.0 license
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2009)

    Objectives

    To examine the prevalence and type of disability in the oldest-old (90+), the fastest growing age group in the United States.

    Methods

    The current study included functional data on 697 participants from The 90+ Study, a population-based longitudinal study of aging and dementia in people aged 90 and older. Data were obtained by participant's informants via a written questionnaire. The prevalence of disability was calculated for two definitions using activities of daily living (ADLs). ADL difficulty was defined as difficulty with one or more ADLs whereas ADL dependency was defined as needing help on one or more ADLs.

    Results

    ADL difficulty was present in 71% in 90-94 year olds, 89% in 95-99 year olds, and 97% in centenarians. ADL dependency was present in 44% of 90-94 year olds, 66% of 95-99 year olds, and 92% of centenarians. The ADL most commonly causing difficulty was walking (70%) whereas the ADL most commonly causing dependency was bathing (51%). Age, gender, and institutionalization were significantly associated with both ADL difficulty and ADL dependency.

    Conclusions

    Similar to studies in younger individuals, the current study suggests that the prevalence of disability continues to increase rapidly in people aged 90 and older. With the rapid growth in the number of people in this age group, disability in the oldest-old has major public health implications.
      Cover page: The prevalence of disability in the oldest‐old is high and continues to increase with age: findings from The 90+ StudyCreative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2011)
        Cover page: BATHING AS A POTENTIAL TARGET FOR DISABILITY REDUCTION IN THE OLDEST OLDCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2011)
          Cover page: Rates of Cognitive Decline and Alzheimer's Disease (AD) Neuropathology in Oldest-OldCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2007)

          Background

          The apolipoprotein E (APOE) epsilon2 allele has been suggested as having a protective effect and delaying the age at onset of Alzheimer disease.

          Objective

          To describe a dissociation between neuropathologic findings with normal cognition in a woman with severe Alzheimer disease with the APOE epsilon2/epsilon2 genotype.

          Design

          Case report from a community-based prospective study of persons 90 years or older (The 90+ Study).

          Participant

          A 92-year-old woman without dementia with the APOE epsilon2/epsilon2 genotype who lived independently without significant cognitive or functional loss and was a participant in The 90+ Study. She died in December 2004, and postmortem examination of her brain was performed.

          Intervention

          Neurologic examination and a battery of neuropsychological tests were performed 6 months and 1 month before death. Neuropathologic examination included Braak and Braak staging for senile plaques and neurofibrillary tangles.

          Results

          Neuropathologic examination of the brain revealed advanced senile plaque and neurofibrillary tangle disease consistent with a high likelihood of Alzheimer disease. At clinical evaluation, the participant demonstrated no dementia and only mild cognitive deficits.

          Conclusions

          The APOE genotype may have contributed to maintenance of cognition despite advanced neuropathologic findings of Alzheimer disease. This case suggests that the APOE epsilon2 isoform may have a protective effect against cognitive decline in Alzheimer disease that may be independent from senile plaques and neurofibrillary tangles.
            Cover page: Dissociation of Neuropathologic Findings and Cognition: Case Report of an Apolipoprotein E ε2/ε2 GenotypeCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2012)

            Objective

            To determine the prevalence and types of cognitive impairment in a sample of nondemented participants aged ≥90 (the oldest-old) and to examine the relationships between cognitive impairment and cardiovascular risk factors.

            Participants

            The participants were 420 nondemented individuals from The 90+ Study, a study of aging and dementia in the oldest-old. These participants were categorized into four nonoverlapping groups: normal cognition, amnestic mild cognitive impairment (aMCI), nonamnestic MCI (naMCI), and other cognitive impairment (OCI). History of cardiovascular risk factors was assessed through self-report.

            Results

            The overall prevalence of cognitive impairment in nondemented participants was 34.0% (95% CI: 29.5-38.5). The prevalence of OCI was highest (17.4%; 95% CI: 13.9-21.4), followed by aMCI (8.3%; 95% CI: 5.9-11.4) and naMCI (8.3%; 95% CI: 5.9-11.4). Normal cognition was present in 66.0% (95% CI: 61.2-70.5) of participants. History of hypertension and stroke were the only risk factors that varied between the groups, occurring more frequently in participants with naMCI (χ(2) = 3.82; P < .05) and OCI (χ(2) = 5.51; P < .05).

            Conclusions

            This study found a high prevalence of cognitive impairment in a sample of nondemented oldest-old. We did not find a strong relationship between cardiovascular risk factors and the cognitive impairment groups, other than between hypertension and naMCI and stroke and OCI. Future studies comparing the incidence of dementia in these groups will ultimately determine their predictive utility in the oldest-old.
              Cover page: Cognitive impairment in nondemented oldest‐old: Prevalence and relationship to cardiovascular risk factorsCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              ICTS Publications (2012)

              : To measure the incidence of disability in individuals aged 90 years and older and examine factors that may increase risk of disability.

              : The 90+ Study, a longitudinal study of aging, initiated in January 2003 with follow-up through May 2009.

              : A total of 216 nondisabled, prospectively followed participants who were aged 90 years or older at baseline.

              : The incidence of disability was measured as needing help on one or more activities of daily living and calculated using person years. Risk factors were examined by using a Cox proportional hazards analysis.

              : The overall incidence of disability was 16.4% per year (95% confidence interval: 13.3-20.0) and did not differ by gender. Disability incidence increased with age from 8.3% in the 90-94 age group to 25.7% in the 95 years and older age group. Several factors were associated with increased risk of disability, including history of congestive heart failure, depression, poor self-rated quality of life, and cognitive impairment.

              : Disability incidence is high and increases rapidly with age in the oldest-old, with rates essentially tripling between ages 90-94 years and 95+ years. Some factors associated with increased risk of disability in younger elderly continue to be risk factors in the oldest-old. Because of the tremendous social and financial impact of disability and the rapid growth of the oldest-old, the development of strategies to delay disability in the elderly should be a priority for healthcare research.

                Cover page: Disability in the oldest-old: incidence and risk factors in the 90+ study.
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2011)

                Objective

                To examine the incidence of dementia among the oldest-old people with normal cognition and different types of cognitive impairment.

                Methods

                This study included 395 participants without dementia (mean age 93.3 years) from The 90+ Study, a prospective, population-based study of aging and dementia in people aged 90 years and older. The participants had evaluations for dementia every 6 months, and their average follow-up was 2.5 years. We examined the incidence of all-cause dementia in participants stratified into 4 cognitive groups: normal, amnestic mild cognitive impairment (aMCI), nonamnestic mild cognitive impairment (naMCI), and other cognitive impairment (OCI).

                Results

                Dementia incidence was highest for participants with aMCI (31.4% per year) and OCI (39.9% per year). Participants with naMCI had an incidence of 14.1% per year, and participants with normal cognition had an incidence of 8.4% per year. Dementia incidence was associated with increasing age in both normal and cognitively impaired participants; however, an APOE4 allele was associated with a higher dementia incidence only in participants with baseline cognitive impairment.

                Conclusions

                The risk of developing dementia in the oldest-old is high and increases to higher rates when cognitive impairment is present. Similar to results of studies in younger elderly individuals, cognitive impairment and increasing age were related to increased dementia incidence. High dementia incidence rates in the oldest-old individuals, particularly when cognitively impaired, emphasize the need to further study cognitive impairment and dementia in this rapidly expanding age group.
                  Cover page: Incidence of dementia in oldest-old with amnestic MCI and other cognitive impairmentsCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  ICTS Publications (2011)
                  Objective

                  To determine the prevalence and types of cognitive impairment in a sample of non-demented aged 90 and older (the oldest-old) and to examine the relationships between cognitive impairment and cardiovascular risk factors.

                  Participants

                  420 non-demented participants from The 90+ Study, a study of aging and dementia in the oldest-old. Participants were categorized into four non-overlapping groups: normal cognition, amnestic mild cognitive impairment (aMCI), non-amnestic MCI (naMCI), and other cognitive impairment (OCI). History of cardiovascular risk factors was assessed through self-report.

                  Results

                  The overall prevalence of cognitive impairment in non-demented was 34.0% (95%CI: 29.5–38.5). The prevalence of OCI was highest (17.4%; 95%CI: 13.9–21.4) followed by aMCI (8.3%; 95%CI: 5.9–11.4) and naMCI (8.3%; 95%CI: 5.9–11.4). Normal cognition was present in 66.0% (95%CI: 61.2–70.5) of participants. History of hypertension and stroke were the only risk factors that varied between the groups, occurring more frequently in participants with naMCI (χ2=3.82; p<0.05) and OCI (χ2=5.51; p<0.05).

                  Conclusions

                  This study found a high prevalence of cognitive impairment in a sample of non-demented oldest-old. We did not find a strong relationship between cardiovascular risk factors and the cognitive impairment groups other than between hypertension and naMCI and stroke and OCI. Future studies comparing the incidence of dementia in these groups will ultimately determine their predictive utility in the oldest-old.

                    Cover page: Cognitive impairment in non-1 demented oldest-old: Prevalence and relationship to cardiovascular risk factors
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2013)

                    Background

                    Although the apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer's disease (AD), it is not clear whether this relationship persists among the oldest old. Several European studies suggest that the effect of the APOE ε4 allele on dementia and mortality disappears in very old age. We describe the APOE allele and genotype frequencies and examine whether the presence of the APOE ε4 or APOE ε2 alleles is related to prevalent dementia, incident dementia, and mortality in a population-based cohort of oldest-old participants in the United States.

                    Methods

                    We studied 904 participants aged 90 years and older from The 90+ Study. Eight hundred two (89%) participants were genotyped and included in the prevalent dementia and mortality analyses. The 520 initially nondemented participants were included in the incident dementia analyses and were evaluated for dementia every 6 months.

                    Results

                    The APOE ε4 allele was significantly associated with prevalent dementia (odds ratio = 2.06) and AD (odds ratio = 2.37) in women but not in men. The APOE ε2 allele was not related to prevalent dementia in either sex. After an average follow-up of 2.4 years, 188 incident dementia cases were identified. Neither the APOE ε4 nor the APOE ε2 allele was related to incident dementia or AD. Five hundred ten (64%) participants died after an average follow-up of 2.3 years, and their mortality was not related to the presence of either the APOE ε2 or APOE ε4 allele.

                    Conclusions

                    Our findings suggest that the associations between APOE ε4, dementia, and mortality are age dependent, and that APOE ε4 no longer plays a role in dementia and mortality at very old ages.
                      Cover page: Apolipoprotein E genotype, dementia, and mortality in the oldest old: The 90+ StudyCreative Commons 'BY' version 4.0 license
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