Alzheimer Disease: Manly JJ

Jarvik L, LaRue A, Blacker D, Gatz M, Kawas C, McArdle JJ, Morris JC, Mortimer JA, Ringman JM, Ercoli L, Freimer N, Gokhman I, Manly JJ, Plassman BL, Rasgon N, Roberts JS, Sunderland T, Swan GE, Wolf PA, Zonderman AB. · Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095, USA. · Alzheimer Dis Assoc Disord. · Pubmed #18317242 No free full text.

Abstract: Children of persons with Alzheimer disease (AD), as a group, face an increased risk of developing AD. Many of them, throughout their adult lives, seek input on how to reduce their chances of one day suffering their parent's fate. We examine the state of knowledge with respect to risk and protective factors for AD and recommend a research agenda with special emphasis on AD offspring.

Acevedo A, Krueger KR, Navarro E, Ortiz F, Manly JJ, Padilla-Vélez MM, Weintraub S, López OL, Mungas D. · Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, MRI Building, 2nd Floor, 4300 Alton Road, Miami Beach, FL 33140, USA. · Alzheimer Dis Assoc Disord. · Pubmed #19474568 No free full text.

Abstract: Researchers from Alzheimer's Disease Centers (ADCs) across the United States with expertise in the assessment of Spanish-speaking elderly collaborated to create the official Spanish version of measures in the Uniform Data Set of the National Institute on Aging Alzheimer's Disease Center Program. The present article describes this project, whose primary goal was to create Spanish instruments with cultural and linguistic equivalence to the English versions. The resulting Spanish versions make provisions for variations among Spanish-speaking groups in the United States of different nationalities, socio-cultural, linguistic, and educational backgrounds. A consensus-based translation and adaptation approach was used, and guiding principles and specific components of this process are summarized. The Spanish translation and adaptation of the Uniform Data Set measures became available online to ADCs in April 2007. Its creation is important, as the resulting effort provides standardized measures for the collection of cross-sectional and longitudinal data on a large cohort of Spanish-speaking elders across the country and facilitates collaborative research among ADCs.

Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. · Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA. · Arch Neurol. · Pubmed #19204158 links to  free full text

Abstract: 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.

Manly JJ, Tang MX, Schupf N, Stern Y, Vonsattel JP, Mayeux R. · Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA. · Ann Neurol. · Pubmed #18300306 links to  free full text

Abstract: OBJECTIVE: To examine incidence rates and antecedents of mild cognitive impairment (MCI) and Alzheimer's disease (AD) among diverse elders without dementia at the initial visit, and to examine the characteristics of elders with MCI who reverted to normal on follow-up examination. METHODS: A total of 2,364 Caribbean Hispanic, black, or non-Hispanic white subjects, aged 65 or older, who were free of dementia at initial evaluation were followed up every 18 to 24 months. Incidence rate of MCI and AD was determined by examination of neurological, medical, psychiatric, and neuropsychological function. RESULTS: Over 10,517 person-years, 21% of normal elderly subjects progressed to MCI (annual incidence rate, 5.1%; 95% confidence interval, 4.6-5.6%). Of those with MCI initially, 21.8% were subsequently diagnosed with AD (annual incidence rate, 5.4%; 95% confidence interval, 4.7-6.3%), 47% remained unchanged, and 31% reverted to normal. Those with MCI were 2.8 times more likely to experience development of AD than normal elderly subjects. MCI with impairment in memory and at least one other cognitive domain was associated with greatest risk for progression to AD and was also least likely to revert to normal at follow-up. Consistent diagnosis of MCI or incident probable or possible AD was 60% sensitive and 94% specific for the pathological diagnosis of AD. INTERPRETATION: Impaired memory and language were useful predictors of transition to AD. Reversion to normal from MCI was frequent, but those with impairment in more than one cognitive domain were more likely to progress or remain impaired than those with single-domain impairment. Clinical diagnosis of MCI does not always predict AD neuropathology.

Luchsinger JA, Reitz C, Patel B, Tang MX, Manly JJ, Mayeux R. · Department of Medicine, Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY 10032, USA. · Arch Neurol. · Pubmed #17420320 links to  free full text

Abstract: BACKGROUND: Type 2 diabetes mellitus is an important risk factor for Alzheimer disease and is more prevalent in elderly minority persons compared with non-Hispanic white persons. OBJECTIVE: To determine whether diabetes is related to a higher risk of mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer disease, in a multiethnic cohort with a high prevalence of diabetes. DESIGN: Longitudinal cohort study. SETTING: Northern Manhattan in New York, NY. PARTICIPANTS: We studied persons without prevalent MCI or dementia at baseline and with at least 1 follow-up interval. Of 1772 participants with a complete neuropsychological evaluation, 339 (19.1%) were excluded because of prevalent dementia, 304 were excluded because of prevalent MCI (17.2%), and 211 were excluded because of loss to follow-up (11.9%), resulting in a final sample of 918 participants for longitudinal analyses. MAIN OUTCOME MEASURES: We related diabetes defined by self-report to incident all-cause MCI, amnestic MCI, and nonamnestic MCI. We conducted multivariate analyses with proportional hazards regression adjusting for age, sex, years of education, ethnic group, apolipoprotein E (APOE) epsilon4 allele, hypertension, low-density lipoprotein level, current smoking, heart disease, and stroke. RESULTS: A total of 334 persons had incident MCI, 160 (47.9%) had amnestic MCI, and 174 (52.1%) had nonamnestic MCI. Diabetes was related to a significantly higher risk of all-cause MCI and amnestic MCI after adjustment for all covariates. Diabetes was also related to a higher risk of nonamnestic MCI, but this association was appreciably attenuated after adjustment for socioeconomic variables and vascular risk factors. The risk of MCI attributable to diabetes was 8.8% for the whole sample and was higher for African American persons (8.4%) and Hispanic persons (11.0%) compared with non-Hispanic white persons (4.6%), reflecting the higher prevalence of diabetes in minority populations in the United States. CONCLUSION: Diabetes is related to a higher risk of amnestic MCI in a population with a high prevalence of this disorder.

Tabert MH, Manly JJ, Liu X, Pelton GH, Rosenblum S, Jacobs M, Zamora D, Goodkind M, Bell K, Stern Y, Devanand DP. · Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, 1051 Riverside Dr, Unit 126, New York, NY 10032, USA. · Arch Gen Psychiatry. · Pubmed #16894068 links to  free full text

Abstract: CONTEXT: The likelihood of conversion to Alzheimer disease (AD) in mild cognitive impairment (MCI) and the "optimal" early markers of conversion need to be established. OBJECTIVES: To evaluate conversion rates to AD in subtypes of MCI and to identify neuropsychological measures most predictive of the time to conversion. DESIGN: Patients were followed up semiannually and controls annually. Subtypes of MCI were determined by using demographically adjusted regression norms on neuropsychological tests. Survival analysis was used to identify the most predictive neuropsychological measures. SETTING: Memory disorders clinic. PARTICIPANTS: One hundred forty-eight patients reporting memory problems and 63 group-matched controls. MAIN OUTCOME MEASURE: A consensus diagnosis of probable AD. RESULTS: At baseline, 108 patients met criteria for amnestic MCI: 87 had memory plus other cognitive domain deficits and 21 had pure memory deficits. The mean duration of follow-up for the 148 patients was 46.6 +/- 24.6 months. In 3 years, 32 (50.0%) of 64 amnestic-"plus" and 2 (10.0%) of 20 "pure" amnestic patients converted to AD (P = .001). In 148 patients, of 5 a priori predictors, the percent savings from immediate to delayed recall on the Selective Reminding Test and the Wechsler Adult Intelligence Scale-Revised Digit Symbol Test were the strongest predictors of time to conversion. From the entire neuropsychological test battery, a stepwise selection procedure retained 2 measures in the final model: total immediate recall on the Selective Reminding Test (odds ratio per 1-point decrease, 1.10; 95% confidence interval, 1.05-1.14; P < .0001) and Digit Symbol Test coding (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .01). The combined predictive accuracy of these 2 measures for conversion by 3 years was 86%. CONCLUSIONS: Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.

Scarmeas N, Albert SM, Manly JJ, Stern Y. · Cognitive Neuroscience Division, Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, 622 West 168th Street, PH 19th Floor, New York, NY 10032, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #16484637 links to  free full text

Abstract: BACKGROUND: Some (but not all) epidemiological studies have noted faster rates of progression in high education patients with Alzheimer's disease (AD), which has been attributed to harbouring/tolerating a higher pathological burden at the time of clinical dementia for subjects with higher education. We wanted to assess the relationship between education and rates of decline in AD. METHODS: During the course of a community based multiethnic prospective cohort study of individuals aged > or = 65 years living in New York, 312 patients were diagnosed with incident AD and were followed overall for 5.6 (up to 13.3) years. The subjects received an average of 3.7 (up to 9) neuropsychological assessments consisting of 12 individual tests. With the aid of a normative sample, a standardised composite cognitive score as well as individual cognitive domain scores were calculated. Generalised estimating equation models were used to examine the association between education and rates of cognitive decline. RESULTS: Composite cognitive performance declined by 9% of a standard deviation per year. Rates of decline before and after AD incidence were similar. For each additional year of education there was 0.3% standard deviation lower composite cognitive performance for each year of follow up. The association between higher education and faster decline was noted primarily in the executive speed (0.6%) and memory (0.5%) cognitive domains and was present over and above age, gender, ethnicity, differential baseline cognitive performance, depression, and vascular comorbidity. CONCLUSIONS: We conclude that higher education AD patients experience faster cognitive decline.

Manly JJ, Bell-McGinty S, Tang MX, Schupf N, Stern Y, Mayeux R. · Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USA. · Arch Neurol. · Pubmed #16286549 links to  free full text

Abstract: BACKGROUND: Reported rates of mild cognitive impairment (MCI) range widely depending on methodologic differences, including specific sample characteristics, cognitive measures used, normative samples used for neuropsychological tests, and diagnostic criteria. OBJECTIVES: To operationalize diagnostic criteria for MCI and examine the frequency of MCI in ethnically and linguistically diverse elders (individuals older than 65 years). DESIGN: Prospective, community-based longitudinal cohort study. SETTING: Northern Manhattan, New York, NY. PARTICIPANTS: A cohort of 1315 nondemented elderly participants. MAIN OUTCOME MEASURE: A diagnosis of MCI was assigned retrospectively on the basis of comprehensive neuropsychological, functional, and neurologic assessments. Amnestic MCI, as well as forms of mild impairment with other cognitive characteristics, were classified. RESULTS: The frequency of amnestic MCI was 5.0% (95% confidence interval, 3.8-6.2). Other subtypes of MCI ranged in frequency from 2.1% to 6.2%. Mild cognitive impairment was more common among those older than 75 years compared with those aged 65 to 75 years. Individuals with fewer than 9 years of schooling were more likely to meet MCI criteria. Apolipoprotein (APOE) E4 allele was more frequent among those with amnestic MCI. CONCLUSIONS: When proper normative values are used, only age and education, and not race or ethnicity, are associated with higher frequency of MCI. The proportion of nondemented elders with isolated memory deficits is smaller than the proportion with deficits in multiple cognitive domains. The strong association of the APOE E4 allele with only amnestic MCI suggests that there are likely to be multiple causes of cognitive impairment and differential rates of conversion to Alzheimer disease within the cognitive subtypes of MCI.

Manly JJ, Espino DV. · Cognitive Neuroscience Division, GH Sergievsky Center and Taub Institute for Research on Alzheimer's Disease & The Aging Brain, Columbia University Health Science Center, 630 West 168th Street, P&S Box 16, New York, NY 10032, USA. · Clin Geriatr Med. · Pubmed #15062490 No free full text.

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Hoskin EK, Tang MX, Manly JJ, Mayeux R. · Gertrude H. Sergievsky Center, Columbia University, New York, NY 10032, USA. · Neurobiol Aging. · Pubmed #14749131 No free full text.

Abstract: BACKGROUND: Hormone levels change significantly with increasing age. These changes may be related to, or be associated with, the emergence of age-related diseases, such as Alzheimer's disease (AD). METHODS: Five hundred and seventy-six women over the age of 65 were studied from the Washington Heights-Inwood Columbia Aging Project (WHICAP). These women were selected from a group of healthy Medicare beneficiaries that were aged 65 and older living in the geographically defined area of northern Manhattan in New York City. Serum levels of estrone (E1), estradiol (E2), total testosterone (TT), dehydroepiandosterone (DHEA), luteinizing hormone (LH), follicle stimulating hormone (FSH), and sex-hormone binding globulin (SHBG) were measured. RESULTS: Significant differences were found between patients with AD and controls only in the level of SHBG, which was 20% higher in patients compared to controls (68.5nmol/l versus 54.7nmol/l, P<0.001). We also estimated levels of total E2 because after menopause, E2 is largely derived from E1. AD patients had significantly lower levels of estimated E2 (AD 0.46 versus controls 0.49, P<0.01). Differences remained significant after adjusting for age, ethnic group, education, and body mass index (BMI). CONCLUSIONS: A marked increase in SHBG levels was found in AD patients. SHBG normally responds to circulating testosterone and estrogen, therefore, elevated SHBG suggests an abnormal increase in its production and regulation. Further work is needed to clarify the cause and consequences of this observation.

Noe E, Marder K, Bell KL, Jacobs DM, Manly JJ, Stern Y. · Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, USA. · Mov Disord. · Pubmed #14743362 No free full text.

Abstract: We compared the clinical and neuropsychological pattern of dementia with Lewy bodies (DLB) to Alzheimer's disease (AD) and Parkinson's 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.

Manly JJ, Merchant CA, Jacobs DM, Small SA, Bell K, Ferin M, Mayeux R. · Department of Neurology, the Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, NY 10032-3702, USA. · Neurology. · Pubmed #10690972 No free full text.

Abstract: BACKGROUND: Although several studies have suggested that hormone replacement therapy lowers the risk of AD among postmenopausal women, few studies have evaluated the relationship of endogenous estrogen levels and AD. The current study investigated whether serum estrone and estradiol levels were related to the presence of AD among postmenopausal women not currently taking hormone replacement therapy. METHODS: Using a case-control design, we examined an ethnically diverse sample of postmenopausal women who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 50) and nondemented controls (n = 93). All women were participants in a study of aging and dementia and were seen consecutively between August 1997 and October 1998. RESULTS: Patients with AD had lower estradiol (F[1,141] = 8.3, p = 0.005) levels than did normal controls. Patients also had lower estrone levels; however, this comparison did not quite meet significance criteria (F[1,141] = 3.6, p = 0.06). Compared to estradiol levels >20 pg/mL, women with AD were four to six times more likely to have levels <20 pg/mL after adjusting for age, years of education, presence of an APOE-epsilon4 allele, ethnicity, and body mass index. There were no significant differences in frequency of AD among women within different quartiles of estrone after adjusting for potential confounds. CONCLUSIONS: The results of this preliminary case-control study suggest that estradiol levels may decline significantly in women in whom AD develops.

Dilworth-Anderson P, Hendrie HC, Manly JJ, Khachaturian AS, Fazio S, Anonymous00219. · Department of Health Policy & Administration, School of Public Health & Institute on Aging, University of North Carolina, Chapel Hill, NC, USA. · Alzheimers Dement. · Pubmed #18631983 No free full text.

This publication has no abstract.