Jennifer J. Manly

Influence of leisure activity on the incidence of Alzheimer’s Disease

Objective: To determine whether leisure activities modify the risk for incident dementia. Background: Although high educational and occupational attainments have been associated with reduced risk of incident dementia, the relation between leisure activities and dementia risk has not been adequately investigated. Methods: A total of 1,772 nondemented individuals aged 65 years or older, living in northern Manhattan, New York, were identified and followed longitudinally in a community-based cohort incidence study. Subjects’ leisure activities at baseline were assessed, annual examinations with the same standardized neurologic and neuropsychological measures were performed for up to 7 years (mean 2.9 years), and incident dementia was assessed as the main outcome measure. Cox proportional hazards models, adjusting for age, ethnic group, education, and occupation, were used to estimate the relative risk (RR) of incident dementia associated with high leisure activities. Results: Of the 1,772 subjects, 207 became demented. The risk of dementia was decreased in subjects with high leisure activities (RR, 0.62; 95% CI 0.46 to 0.83). The association of high leisure with decreased RR of incident dementia was present even when baseline cognitive performance, health limitations interfering with desired leisure activities, cerebrovascular disease, and depression were considered. Conclusions: The data suggest that engagement in leisure activities may reduce the risk of incident dementia, possibly by providing a reserve that delays the onset of clinical manifestations of the disease.

Mediterranean Diet and Mild Cognitive Impairment

BACKGROUND Higher adherence to the Mediterranean diet (MeDi) may protect from Alzheimer disease (AD), but its association with mild cognitive impairment (MCI) has not been explored. OBJECTIVE To investigate the association between the MeDi and MCI. DESIGN, SETTING, AND PATIENTS In a multiethnic community study in New York, we used Cox proportional hazards to investigate the association between adherence to the MeDi (0-9 scale; higher scores indicate higher adherence) and (1) the incidence of MCI and (2) the progression from MCI to AD. All of the models were adjusted for cohort, age, sex, ethnicity, education, APOE genotype, caloric intake, body mass index, and duration between baseline dietary assessment and baseline diagnosis. MAIN OUTCOME MEASURES Incidence of MCI and progression from MCI to AD. RESULTS There were 1393 cognitively normal participants, 275 of whom developed MCI during a mean (SD) follow-up of 4.5 (2.7) years (range, 0.9-16.4 years). Compared with subjects in the lowest MeDi adherence tertile, subjects in the middle tertile had 17% less risk (hazard ratio [HR] = 0.83; 95% confidence interval [CI], 0.62-1.12; P = .24) of developing MCI and those in the highest tertile had 28% less risk (HR = 0.72; 95% CI, 0.52-1.00; P = .05) of developing MCI (trend HR = 0.85; 95% CI, 0.72-1.00; P for trend = .05). There were 482 subjects with MCI, 106 of whom developed AD during a mean (SD) follow-up of 4.3 (2.7) years (range, 1.0-13.8 years). Compared with subjects in the lowest MeDi adherence tertile, subjects in the middle tertile had 45% less risk (HR = 0.55; 95% CI, 0.34-0.90; P = .01) of developing AD and those in the highest tertile had 48% less risk (HR = 0.52; 95% CI, 0.30-0.91; P = .02) of developing AD (trend HR = 0.71; 95% CI, 0.53-0.95; P for trend = .02). CONCLUSIONS Higher adherence to the MeDi is associated with a trend for reduced risk of developing MCI and with reduced risk of MCI conversion to AD.

Plasma Aβ40 and Aβ42 and Alzheimer's Disease: Relation to Age, Mortality, and Risk

BackgroundPlasma amyloid &bgr;-peptide (A&bgr;) 40 and A&bgr;42 levels are increased in persons with mutations causing early-onset familial Alzheimer’s disease (AD). Plasma A&bgr;42 levels were also used to link microsatellite genetic markers to a putative AD genetic locus on chromosome 10 and were observed in patients with incipient sporadic AD. MethodsThe authors measured plasma A&bgr;40 and A&bgr;42 levels using a sandwich ELISA after the initial examination of 530 individuals participating in an epidemiologic study of aging and dementia. Participants were examined at 18-month intervals, and plasma A&bgr;40 and A&bgr;42 levels were repeated in 307 subjects 3 years after baseline. ResultsCompared with individuals who never developed AD, patients with AD at baseline and those who developed AD during the follow-up had significantly higher A&bgr;42, but not A&bgr;40, plasma levels. The risk of AD in the highest quartile of plasma A&bgr;42 was increased by more than twofold over that in the lowest quartile. The highest plasma A&bgr;42 levels were observed in patients with AD who died during the follow-up. Plasma A&bgr;42, but not A&bgr;40, levels decreased over time in patients with newly acquired AD. ConclusionsPlasma A&bgr;40 and A&bgr;42 increase with age and are strongly correlated with each other. Plasma A&bgr;40 and A&bgr;42 levels are elevated in some patients before and during the early stages of AD but decline thereafter. High plasma A&bgr;42 levels may also be associated with mortality in patients with AD.

Reading level attenuates differences in neuropsychological test performance between African American and White elders

The current study sought to determine if discrepancies in quality of education could explain differences in cognitive test scores between African American and White elders matched on years of education. A comprehensive neuropsychological battery was administered to a sample of African American and non-Hispanic White participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and had no history of Parkinsons disease, stroke, mental illness, or head injury. The Reading Recognition subtest from the Wide Range Achievement Test-Version 3 was used as an estimate of quality of education. A MANOVA revealed that African American elders obtained significantly lower scores than Whites on measures of word list learning and memory, figure memory, abstract reasoning, fluency, and visuospatial skill even though the groups were matched on years of education. However, after adjusting the scores for WRAT-3 reading score, the overall effect of race was greatly reduced and racial differences on all tests (except category fluency and a drawing measure) became nonsignificant. These findings suggest that years of education is an inadequate measure of the educational experience among multicultural elders, and that adjusting for quality of education may improve the specificity of certain neuropsychological measures.

Plasma amyloid β-peptide 1–42 and incipient Alzheimer's disease

Mutations in the amyloid precursor protein and presenilin 1 and 2 genes result in elevated plasma levels of the amyloid β‐peptide species terminating at amino acid residue 42 (Aβ1–42). In a longitudinal study of unrelated elderly individuals, those who subsequently developed Alzheimers disease had higher plasma levels of Aβ1–42 at entry than did those who remained free of dementia. The results indicate that elevated plasma levels of the released Aβ peptide Aβ1–42 may be detected several years before the onset of symptoms, supporting that extracellular Aβ1–42 plays an important role in the pathogenesis of late‐onset Alzheimers disease.

Cognition assessment using the NIH Toolbox

Vision is a sensation that is created from complex processes and provides us with a representation of the world around us. There are many important aspects of vision, but visual acuity was judged to be the most appropriate vision assessment for the NIH Toolbox for Assessment of Neurological and Behavioral Function, both because of its central role in visual health and because acuity testing is common and relatively inexpensive to implement broadly. The impact of visual impairments on health-related quality of life also was viewed as important to assess, in order to gain a broad view of ones visual function. To test visual acuity, an easy-to-use software program was developed, based on the protocol used by the E-ETDRS. Children younger than 7 years were administered a version with only the letters H, O, T, and V. Reliability and validity of the Toolbox visual acuity test were very good. A 53-item vision-targeted, health-related quality of life survey was also developed.

Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease

Plasma Aβ42 and Aβ40 levels are putative biomarkers for Alzheimers disease (AD), but their significance and predictive value have been inconclusive. In AD transgenic models, plasma and cerebrospinal fluid levels of Aβ42 and Aβ40 increase with age but subsequently decrease when Aβ begins to accumulate in brain and with the onset of cognitive impairment. To determine the predictive value of Aβ levels in elderly populations, we investigated how plasma Aβ42, Aβ40, and a protofibrillar subspecies of Aβ42 changed over time and with the onset of cognitive impairment or AD. In a cohort of 1,125 elderly persons without dementia, 104 (9.2%) of the participants developed AD over 4.6 years of follow-up. Higher plasma Aβ42 levels at the onset of the study were associated with a threefold increased risk of AD. However, conversion to AD was accompanied by a significant decline in plasma Aβ42, a decreased Aβ42/Aβ40 ratio and, with the onset of cognitive impairment, decreased protofibrillar Aβ42 levels. Our results suggest individuals with elevated plasma Aβ42 are at increased risk of AD and that with the onset of disease, the decline in some forms of Aβ may reflect compartmentalization of Aβ peptides in the brain.

Effect of literacy on neuropsychological test performance in nondemented, education-matched elders

The current investigation compared neuropsychological test performance among nondemented literate and illiterate elders. The sample included participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and did not have history of Parkinsons disease, stroke, or head injury. Literacy level was determined by self-report. MANOVAs revealed a significant overall effect for literacy status (literate vs. illiterate) on neuropsychological test performance when groups were matched on years of education. The overall effect of literacy status remained significant after restricting the analyses to elders with no formal education, and after controlling for the effects of language of test administration. Specifically, illiterates obtained lower scores on measures of naming, comprehension, verbal abstraction, orientation, and figure matching and recognition. However tests of verbal list delayed recall, nonverbal abstraction, and category fluency were unaffected by literacy status, suggesting that these measures can be used to accurately detect cognitive decline among illiterate elders in this sample. Differences in organization of visuospatial information, lack of previous exposure to stimuli, and difficulties with interpretation of the logical functions of language are possible factors that contribute to our findings.

Comparison of dementia with Lewy bodies to Alzheimer's disease and Parkinson's disease with dementia.

We compared the clinical and neuropsychological pattern of dementia with Lewy bodies (DLB) to Alzheimers disease (AD) and Parkinsons disease with dementia (PD‐d). Sixteen patients clinically diagnosed with DLB were compared with two groups of patients with PD‐d (n = 15) and AD (n = 16) matched for level of dementia. Isolated cognitive impairment was the most common form of presentation in AD (93.8%) and DLB (31.3%) groups, while parkinsonism was in 100% of PD‐d subjects. Psychoses associated with cognitive impairment at the beginning of the disease were more frequent in DLB patients (31.3%) than in AD (6.3%) and PD‐d (0%) groups. There were no significant differences in Unified Parkinson Disease Rating Scale motor‐subscale scores between DLB and PD‐d patients. DLB and PD‐d patients performed significantly worse on attentional functions and better on memory tests than AD. DLB patients also showed lower scores than AD subjects on visual memory, visuoperceptive, and visuoconstructive tests. No significant differences were found between PD‐d group and DLB subjects on any neuropsychological test. We were unable to find any differences in cognitive tasks between PD‐d and DLB subjects. Clinical features and neuropsychological deficiencies of DLB (attentional, visuoperceptive, and visuoconstructive deficits) and PD (attentional deficits) compared to AD (amnesic syndrome) can contribute to accurate identification of these entities and to the understanding of the neuropathological and neurochemical substrate underlying these diseases.

Literacy and Memory Decline among Ethnically Diverse Elders

Literacy may be a more powerful indicator of brain reserve than years of education. Literacy level may be a proxy for native intellectual capacity or life experience that can compensate for brain damage or provide brain reserve. Alternately, the experience of acquiring literacy skills may in itself change the organization of the brain and increase protection against cognitive decline. However, because people with low levels of literacy obtain poor scores on most cognitive measures, only longitudinal studies can elucidate the role of reading ability in reserve. We determined whether literacy skills could predict cognitive change in a sample of 136 English-speaking African American, Caucasian, and Hispanic elders selected from a longitudinal aging study in New York City. According to a physician’s independent examination, all participants were nondemented throughout the four longitudinal assessments. Literacy level was assessed using the WRAT-3 reading subtest. After accounting for age at baseline and years of education, GEE analyses showed that elders with low levels of literacy had a steeper decline in both immediate and delayed recall of a word list over time as compared to high literacy elders. Our findings suggest that literacy skills are protective against memory decline among nondemented elders.