Alzheimer Disease: Gatz M

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.

Gatz M, Prescott CA, Pedersen NL. · Department of Psychology, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089-1061, USA. · Alzheimer Dis Assoc Disord. · Pubmed #16917202 No free full text.

Abstract: Research findings suggest that dementia risk is lower in individuals with more extensive education, greater engagement in mentally stimulating leisure activities during adulthood, and higher occupational complexity. Other recent findings support the importance of early-life risk factors, such as socioeconomic conditions, early-life development, and exposure to infection, in explaining individual differences in dementia risk. Life-style variables have been conceptualized as delaying factors, postponing onset of dementia and thereby reducing total population burden of dementia. Using a sample of Swedish twins from the HARMONY study, we found that education significantly affects dementia onset, that is, occurrence and timing of dementia symptoms. In the HARMONY data, we also showed that differences in education are reflected in differences in leisure activities and occupation, suggesting that differences in cognitive engagement begin early and persist over the life course. Such findings point to the importance of taking a life-course perspective to designing interventions to delay or to prevent dementia.

Chui HC, Gatz M. · Department of Neurology, University of Southern California Los Angeles, California, USA. · Alzheimer Dis Assoc Disord. · Pubmed #16327354 No free full text.

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Xu W, Qiu C, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. · Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm, Sweden. · Diabetes. · Pubmed #18952836 links to  free full text

Abstract: OBJECTIVE: We aimed to verify the association between diabetes and the risk of dementia, Alzheimer's disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association. RESEARCH DESIGN AND METHODS: This study included 13,693 twin individuals aged > or =65 years. Dementia was diagnosed according to DSM-IV (Diagnostic Manual of Mental Disorders, 4th ed.) criteria. Information on diabetes was collected from the inpatient registry and self- or informant-reported history of diabetes. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models and 2) cotwin matched case-control analysis for dementia-discordant twin pairs using conditional logistic regression. RESULTS: Of all participants, 467 were diagnosed with dementia, including 292 with Alzheimer's disease and 105 with vascular dementia, and an additional 170 were diagnosed with questionable dementia. Diabetes was present in 1,396 subjects. In GEE models, diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51-2.38) for dementia, 1.69 (1.16-2.36) for Alzheimer's disease, and 2.17 (1.36-3.47) for vascular dementia. Compared with late-life diabetes (onset age > or =65 years), the risk effect of mid-life diabetes (onset age <65 years) on dementia was stronger. Conditional logistic analysis of 210 dementia-discordant twin pairs led to ORs of 2.41 (1.05-5.51) and 0.68 (0.30-1.53) for dementia related to mid- and late-life diabetes, respectively. CONCLUSIONS: Diabetes increases the risk of Alzheimer disease and vascular dementia. The risk is stronger when diabetes occurs at mid-life than in late life. Genetic and early-life environmental factors might contribute to the late-life diabetes-dementia association but could not account for the mid-life diabetes-dementia association.

Blom ES, Holmans P, Arepalli S, Adighibe O, Hamshere ML, Gatz M, Pedersen NL, Bergem AL, Owen MJ, Hollingworth P, Goate A, Williams J, Lannfelt L, Hardy J, Wavrant-De Vrièze F, Glaser A. · Section of Molecular Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #18161859 No free full text.

Abstract: We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer's disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multipoint linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well explained by APOE in the whole sample as well as in the UK and USA subsamples, as identity by descent (IBD) increased with the number of epsilon4 alleles in ASPs. There was a suggestion from the SWE subsample that linkage was higher than would be expected from APOE alone, although the test for this did not reach formal statistical significance. There was also a significant age at onset (aao) effect on linkage to chromosome 19q13 in the whole sample, which manifested itself as increased IBD sharing in relative pairs with lower mean aao. This effect was partially, although not completely, explained by APOE. The aao effect varied considerably between the different subsamples, with most of the effect coming from the UK sample. The other samples showed smaller effects in the same direction, but these were not significant.

Eriksson UK, Gatz M, Dickman PW, Fratiglioni L, Pedersen NL. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #18097143 No free full text.

Abstract: BACKGROUND: Inflammation is associated with Alzheimer's disease (AD) and dementia. In light of the chronic inflammatory properties of the atopic disorders asthma, eczema and rhinitis, we hypothesized an association with dementia. METHODS: Self-reported asthma, eczema or rhinitis was assessed (prior to dementia follow-up) through questionnaires in the 1960s or 1970s in twins from the population-based Swedish Twin Registry. Dementia was assessed both longitudinally (n = 22,188), through linkages to two population-based registers, and cross-sectionally (n = 7,800), through telephone cognitive screening followed by a clinical evaluation of suspects of dementia. Risk ratios were estimated with Cox and logistic regression models controlling for vascular disease and genetic confounding. RESULTS: In the longitudinal study, a history of atopy was positively associated with dementia (HR = 1.16; 1.01-1.33). In the cross-sectional study we found overall lower risks, none of which was statistically significant. Asthma was associated with a shorter survival time following AD onset. CONCLUSIONS: Atopy is associated with a modestly increased risk of AD and dementia that is not mediated by vascular disease or due to genetic confounding. A history of asthma is associated with shorter life expectancy after AD diagnosis.

Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A, Pedersen NL. · Department of Psychology, University of Southern California, Los Angeles 90089-1061, USA. · Arch Gen Psychiatry. · Pubmed #16461860 links to  free full text

Abstract: CONTEXT: Twin studies using selected samples have shown high heritability for Alzheimer disease (AD). OBJECTIVE: To evaluate genetic and environmental influences on AD in a fully ascertained population of older twins, including like- and unlike-sex pairs. DESIGN: Five-group quantitative genetic model: male monozygotic twins, female monozygotic twins, male dizygotic twins, female dizygotic twins, and unlike-sex twins. SETTING AND PARTICIPANTS: All twins in the Swedish Twin Registry aged 65 years and older. The study included 11,884 twin pairs, among whom were 392 pairs in which 1 or both members had AD. MAIN OUTCOME MEASURES: All individuals were screened for cognitive dysfunction. Suspected cases of dementia and their co-twins received complete clinical diagnostic evaluations for AD. Estimates of heritability, shared environmental influences, and nonshared environmental influences, adjusting for age, were derived from the twin data. RESULTS: Heritability for AD was estimated to be 58% in the full model and 79% in the best-fitting model, with the balance of variation explained by nonshared environmental influences. There were no significant differences between men and women in prevalence or heritability after controlling for age. Within pairs concordant for AD, intrapair difference in age at onset was significantly greater in dizygotic than in monozygotic pairs, suggesting genetic influences on timing of the disease. CONCLUSIONS: In the largest twin study to date, we confirmed that heritability for AD is high and that the same genetic factors are influential for both men and women. However, nongenetic risk factors also play an important role and might be the focus for interventions to reduce disease risk or delay disease onset.

Andel R, Vigen C, Mack WJ, Clark LJ, Gatz M. · School of Aging Studies, University of South Florida, Tampa, Florida 33620, USA. · J Int Neuropsychol Soc. · Pubmed #16433954 No free full text.

Abstract: We explored the effect of education and occupational complexity on the rate of cognitive decline (as measured by the Mini-Mental State Examination) in 171 patients with a confirmed Alzheimer's disease (AD) diagnosis. Complexity was measured as substantive complexity of work and complexity of work with data, people, and things. Average lifetime occupational complexity was calculated based on years at each occupation. Participants were followed for an average of 2.5 years and 3.7 visits. In multivariate mixed-effects models, high education, high substantive complexity, and high complexity of work with data and people predicted faster rates of cognitive decline, controlling for age, gender, native language, dementia severity, and entry into the analyses at initial versus follow-up testing. These results provide support for the concept of cognitive reserve according to which greater reserve may postpone clinical onset of AD but also accelerate cognitive decline after the onset.

Reynolds CA, Prince JA, Feuk L, Brookes AJ, Gatz M, Pedersen NL. · Department of Psychology, University of California--Riverside, 92521, USA. · Behav Genet. · Pubmed #16402284 No free full text.

Abstract: The APOE gene (apolipoprotein E) is a major risk factor for Alzheimer's Disease (AD) but has been inconsistently associated with memory in nondemented adults. Two other genes with mixed support as genetic risk factors for AD, A2M (alpha-2-macroglobulin) and LRP (low-density lipoprotein receptor-related protein), have not been studied in relation to memory among nondemented adults. The present study examined these three genes and latent growth parameters estimated from memory performance spanning 13 years in 478 twins from the Swedish Adoption/Twin Study of Aging (SATSA). APOE was associated with working and recall memory ability levels and working memory rate of change, with e4 homozygotes exhibiting the worst performance at all ages. Homozygotes for the rare A2M insertion/deletion variant exhibited accelerating decline on delayed figural recognition. There were no significant findings for LRP. Dominance, often untested in previous studies, was important in the current study's findings.

Andel R, Crowe M, Pedersen NL, Mortimer J, Crimmins E, Johansson B, Gatz M. · School of Aging Studies MHC 1321, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #16131619 No free full text.

Abstract: We examined the association between risk of dementia or Alzheimer's disease (AD) and occupation by using measures of complexity of work with data, people, and things. The study included 10,079 members of the population-based Swedish Twin Registry who were participants in the HARMONY study. We diagnosed dementia by means of a two-stage procedure--cognitive impairment screening followed by full clinical evaluation. We analyzed data with case-control and cotwin control designs. The cotwin control design provides control over genetic and familial factors. In the case-control study, controlling for age, gender, and level of education, we found that more complex work with people was associated with reduced risk of AD. Greater complexity of work with people and data was protective in twin pairs discordant for AD. Findings suggest that greater complexity of work, and particularly complex work with people, may reduce the risk of AD.

Fiske A, Gatz M, Aadnøy B, Pedersen NL. · Department of Psychology, University of Southern California, Los Angeles, California, USA. · Alzheimer Dis Assoc Disord. · Pubmed #16118529 No free full text.

Abstract: Age of onset is an important variable in Alzheimer research, yet remarkably little is known about its reliability and validity. The present study evaluated alternative methods for establishing age of onset for 297 individuals diagnosed with dementia through the HARMONY study. We compared two informant-based methods: a single question in a telephone screening interview and an in-depth, semi-structured, in-person interview. We then compared informant reports with medical records. The two informant-based methods yielded very similar results, r(297) = .89 (P < .0001). Informant reports were highly correlated with age of diagnosis in medical records, r(155) = .88 (P < 0.0001) for the single question, r(201) =.89 (P < .0001) for the in-depth interview. Age of diagnosis in the medical records lagged consistently 2.9 and 2.7 years behind age of onset from screening and in-depth interviews, respectively. Greater lag was associated with longer time since dementia onset, whether due to recall bias or improved detection of dementia. Lag was not influenced by dementia type, informant's relationship to proband, or proband's age. These findings suggest that informant reports of age of dementia onset are reliable and reasonably valid, even when only a single question is asked within the context of a larger interview.

Gatz M. · Department of Psychology, University of Southern California, Los Angeles, California, USA. · PLoS Med. · Pubmed #15696217 links to  free full text

This publication has no abstract.

Gatz M, Fratiglioni L, Johansson B, Berg S, Mortimer JA, Reynolds CA, Fiske A, Pedersen NL. · Department of Psychology, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089-1061, USA. · Neurobiol Aging. · Pubmed #15653172 No free full text.

Abstract: The purpose of this report is to describe the Study of Dementia in Swedish Twins (known as HARMONY), including procedures for complete ascertainment of all cases of Alzheimer's disease (AD) and other dementias in 14,435 individuals aged 65 and older from the national Swedish twin registry. Telephone cognitive screening identified 11.5% as positive for cognitive dysfunction. Clinical diagnoses were completed for 1557 individuals, including individuals who screened positive, their twin partners, and a sample of normal controls. Estimated prevalence of dementia ranged from 1.4% for age 65-69 to 29.2% for age 90 and older. Concordance rates for Alzheimer's disease were 59% for monozygotic twins, 32% for like-sexed, and 24% for unlike-sexed dizygotic twins. Among monozygotic twins where both twins had Alzheimer's disease, the within pair difference in age of onset ranged from both becoming demented in the same year to 7 years difference in onset.

Katzov H, Bennet AM, Kehoe P, Wiman B, Gatz M, Blennow K, Lenhard B, Pedersen NL, de Faire U, Prince JA. · Center for Genomics and Bioinformatics, Karolinska Institute, Berzelius väg 35 171 77, Stockholm, Sweden. · Hum Mol Genet. · Pubmed #15367486 links to  free full text

Abstract: Sequence variation in ACE, which encodes angiotensin I converting enzyme, contributes to a large proportion of variability in plasma ACE levels, but the extent to which this impacts upon human disease is unresolved. Most efforts to associate ACE with other heritable traits have involved a single Alu insertion/deletion polymorphism, despite the probable existence of other functional sequence variants with effects that may not be consistently detectable by solely typing the Alu indel. Here, utilizing single nucleotide polymorphisms (SNPs) that differentiate major ACE clades in European populations, we demonstrate a number of significant phenotype associations across more than 4000 Swedish individuals. In a systematic analysis of metabolic phenotypes, effects were detected upon several traits, including fasting plasma glucose levels, insulin levels and measures of obesity (P-values ranging from 0.046 to 8.4 x 10(-6)). Extending cladistic models to the study of myocardial infarction and Alzheimer disease, significant associations were observed with greater effect sizes than those typically obtained in large-scale meta-analyses based on the Alu indel. Population frequencies of ACE genotypes were also found to change with age, congruent with previous data suggesting effects upon longevity. Clade models consistently outperformed those based upon single markers, reinforcing the importance of taking into consideration the possible confounding effects of allelic heterogeneity in this genomic region. Utilizing computational tools, potential functional variants are highlighted that may underlie phenotypic variability, which is discussed along with the broader implications these results may have for studies attempting to link variation in ACE to human disease.

Jin YP, Gatz M, Johansson B, Pedersen NL. · Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. · Neurology. · Pubmed #15326258 No free full text.

Abstract: The authors investigated the sensitivity and specificity of dementia identification in two Swedish disease registries by using clinical diagnoses from two population-based studies as gold standards. The probability of dementia detected by the Inpatient Discharge Registry was 55% for prevalent patients and 31% for incident patients and was higher than detection by the Cause of Death Registry. Specificity was 98% for the Inpatient Discharge Registry and 100% for the Cause of Death Registry.

Katzov H, Chalmers K, Palmgren J, Andreasen N, Johansson B, Cairns NJ, Gatz M, Wilcock GK, Love S, Pedersen NL, Brookes AJ, Blennow K, Kehoe PG, Prince JA. · Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden. · Hum Mutat. · Pubmed #15024730 No free full text.

Abstract: Linkage studies have provided evidence that one or more loci on chromosome 9q influence Alzheimer disease (AD). The gene encoding the ATP-binding cassette A1 transporter (ABCA1) resides within proximity of previously identified linkage peaks and represents a plausible biological candidate for AD due to its central role in cellular lipid homeostasis. Several single nucleotide polymorphisms (SNPs) spanning ABCA1 have been genotyped and haplotype-based association analyses performed in four independent case-control samples, consisting of over 1,750 individuals from three European populations representing both early and late-onset AD. Prominent effects were observed for a common (H2) and rarer haplotype (H5) that were enriched in AD cases across studied populations (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.36-1.82; P<0.00001 and OR 2.90; 95% CI 2.54-3.27; P<0.00001, respectively). Two other common haplotypes in the studied region (H1 and H3) were significantly under-represented in AD cases, suggesting that they may harbor alleles that decrease disease risk (OR 0.79, 95% CI 0.64-0.94; P=0.0065 and OR 0.70, 95% CI 0.46-0.93; P=0.011, respectively). While findings were significant in both early and late-onset samples, haplotype effects were more distinct in early-onset materials. For late-onset samples, ancillary evidence was obtained that both single marker alleles and haplotypes of ABCA1 contribute to variable cerebrospinal fluid tau and beta amyloid (Abeta42) protein levels, and brain Abeta load. Results indicate that variants of ABCA1 may affect the risk of AD, providing further support for a genetic link between AD and cholesterol metabolism.

Watari KF, Gatz M. · Department of Psychology, University of Southern California, Los Angeles, CA, USA. · Cultur Divers Ethnic Minor Psychol. · Pubmed #14992628 No free full text.

Abstract: Little is known about how Korean Americans make decisions whether to seek help when, experiencing symptoms that might signal dementia. In Study 1, patient registry data for 60 Korean and 212 non-Korean Alzheimer's disease patients revealed that both groups waited 3-4 years before seeking help and sought help when memory decline was accompanied by other problems. Among Korean Americans, those living with family were more impaired than those living alone, suggesting greater, delay in seeking help. In Study 2, 109 Korean Americans ages 18-73 were surveyed concerning acculturation, knowledge, and help-seeking attitudes. Those more familiar with dementia symptoms indicated they would seek help, supporting the value of public education.

Kehoe PG, Katzov H, Andreasen N, Gatz M, Wilcock GK, Cairns NJ, Palmgren J, de Faire U, Brookes AJ, Pedersen NL, Blennow K, Prince JA. · Department of Care of the Elderly, The John James Building, Frenchay Hospital, University of Bristol, UK. · Hum Genet. · Pubmed #14986105 No free full text.

Abstract: Studies on the role that genetic variation may play in a complex human disease can be empowered by an assessment of both disease risk in case-control or family models and of quantitative traits that reflect elements of disease etiology. An excellent example of this can be found for the epsilon4 allele of APOE in relation to Alzheimer's disease (AD) for which association with both risk and age-at-onset (AAO) is evident. Following a recent demonstration that variants of the gene encoding angiotensin I converting enzyme ( ACE) contribute to AD risk, we have explored the potential influence of ACE upon AAO in AD. A total of 2861 individuals from three European populations, including six independent AD samples, have been examined in this study. Three single nucleotide polymorphisms (SNPs) previously demonstrated to have maximum effects upon ACE plasma levels and that span the ACE locus were genotyped in these materials. A strong effect upon AAO was observed for marker rs4343 in exon 17 ( P<0.0001), but evidence was also obtained indicating a possible independent effect of marker rs4291 ( P=0.0095) located in the ACE promoter. Effects were consistent with data from previous studies suggesting association with AD in case-control models, whereby alleles demonstrated to confer risk to disease also appear to reduce AAO. Equivalent effects were evident regardless of APOE epsilon4 carrier status and in both males and females. These results provide an important complement to existing AD risk data, confirming that ACE harbors sequence variants that contribute to aspects of AD pathology.

Pedersen NL, Gatz M, Berg S, Johansson B. · Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden. · Ann Neurol. · Pubmed #14755721 No free full text.

Abstract: Although genetic effects are known to be important for early onset Alzheimer's disease, little is known about the importance of genetic effects for late-onset disease. Furthermore, previous studies are based on prevalent cases. Our purpose was to characterize the relative importance of genetic and environmental factors for incident Alzheimer's disease late in life, and to test for differences in the importance of genetic effects at different ages. A cohort of 662 pairs of Swedish twins 52 to 98 years of age who were without symptoms of dementia was followed up for an average of 5 years. Incident dementia cases were detected through follow-up at 2 to 3-year intervals using either cognitive testing or telephone screening followed by dementia workups. A physician, psychologist, and nurse gave consensus diagnoses. During the follow-up period, 5.8% of the sample was diagnosed with Alzheimer's disease. Average age of onset was 83.9 years (standard deviation, 6.3). Of the 26 monozygotic pairs in which at least one twin developed Alzheimer's disease, 5 were concordant (probandwise concordance, 32.2%). The concordance rate for dizygotic pairs was 8.7% (2 of 44 pairs). Structural model fitting indicated that 48% of the variation in liability to Alzheimer's disease could be attributed to genetic variation. Estimates did not differ significantly between twins younger than age 80 years and those older than age 80 years at baseline. Although these genetic estimates for incident disease are lower than those for prevalent disease, the importance of genetic factors for liability to Alzheimer's disease is considerable even late in life.

Gatz M, Fiske A, Reynolds CA, Wetherell JL, Johansson B, Pedersen NL. · University of Southern California, Los Angeles, California, USA. Karolinska Institutet, Stockholm, Sweden. · Behav Genet. · Pubmed #14574145 No free full text.

Abstract: We used two Swedish twin samples to test whether women are at greater risk than men of developing dementia and whether there are sex differences in mechanisms underlying dementia and cognitive dysfunction. Dementia analyses found no sex differences in incidence of dementia or Alzheimer's disease among initially intact participants followed longitudinally. Twin analyses indicated a substantial genetic influence on liability to incident dementia. Although sex differences in model parameters were not statistically significant, for women but not men an equally attractive model included genetic influence due to both additive effects and dominance or epistasis. In the cognitive dysfunction analyses, results from a sex limitation model raise the possibility that either different genes or different environments have a role for men and women. We conclude that women are not at higher risk of developing dementia, but there is a hint that different genetic processes may be involved for women than for men.

Prince JA, Feuk L, Gu HF, Johansson B, Gatz M, Blennow K, Brookes AJ. · Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden. · Hum Mutat. · Pubmed #14517947 No free full text.

Abstract: Linkage studies have identified a large (>60-Mb) region on chromosome 10q that segregates with Alzheimer Disease (AD). Within the region, the gene for insulin degrading enzyme (IDE) represents a notable biological candidate given that it degrades amyloid beta-protein (one of the major constituents of senile plaques) and the intracellular amyloid precursor protein (APP) domain released by gamma-secretase processing. We have used a single nucleotide polymorphism (SNP) genetic association strategy to investigate AD in relation to a 480-kb region encompassing IDE. A 276-kb linkage disequilibrium block was revealed that spans three genes (IDE, KNSL1, and HHEX). Assessing this block in several independent sets of case-control materials (early- and late-onset AD) and focusing also upon quantitative measures that are pertinent to AD diagnosis and severity (MMSE scores, microtubule-associated protein Tau [MAPT] levels in CSF, degree of brain pathology, and age-at-onset) produced extensive evidence for significant AD association. Signals (p-values ranging from 0.05 to <1x10(-9)) were generally stronger when examining haplotypes rather than individual SNPs, and quantitative trait tests most uniformly revealed the detected associations. Consistent risk alleles and haplotypes were apparent across the study, with effects in some cases as large as that of the epsilon4 allele of APOE. A subsequent mutation screen of exons in all three suspect genes provided no evidence for common causative mutations. These results provide substantial evidence that genetic variation within or extremely close to IDE impacts both disease risk and traits related to the severity of AD.

Crowe M, Andel R, Pedersen NL, Johansson B, Gatz M. · Department of Psychology. Leonard Davis School of Gerontology, University of Southern California, Los Angeles 90089-1061, USA. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #14507930 No free full text.

Abstract: This study examined whether participation in leisure activities during early and middle adulthood was associated with reduced risk of Alzheimer's disease. The sample consisted of 107 same-sex twin pairs discordant for dementia and for whom information on leisure activities was self-reported more than 20 years prior to clinical evaluation. A factor analysis of these activities yielded three activity factors: intellectual-cultural, self-improvement, and domestic activity. Matched-pair analyses compared activities within the discordant twin pairs while controlling for level of education. For the total sample, participation in a greater overall number of leisure activities was associated with lower risk of both Alzheimer's disease and dementia in general. Greater participation in intellectual-cultural activities was associated with lower risk of Alzheimer's disease for women, although not for men.

Andel R, McCleary CA, Murdock GA, Fiske A, Wilcox RR, Gatz M. · Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089, USA. · Int J Geriatr Psychiatry. · Pubmed #12891642 No free full text.

Abstract: BACKGROUND: Evaluation of patients for Alzheimer's disease often compares an individual's performance on cognitive tests to established norms. The purpose of this study was to compare performance on the CERAD Word List Memory tasks in normal controls from an Alzheimer's disease registry and in community volunteers. METHODS: Scores on Word List Memory tasks were evaluated in cognitively intact participants enrolled in a university-based Alzheimer's disease registry (n=103) and in a sample of community volunteers (n=51). Scores for the two samples were also compared with previously published data from registry-based normal controls and from a representative community-based sample. RESULTS: University-based participants outperformed community volunteers, with most marked differences on Delayed Recall and on a Savings score that contrasted immediate to delayed recall. University-based participants performed similarly to previously published scores for normal controls from another university-based Alzheimer's disease registry, while community volunteers were consistent with published scores available from a representative community sample. CONCLUSIONS: Accurate neuropsychological assessment of Alzheimer's disease may require consideration of potentially subtle differences between older adults tested at university centers and those tested in the community.

Gatz M, Reynolds CA, John R, Johansson B, Mortimer JA, Pedersen NL. · Department of Psychology, University of Southern California, Los Angeles, California 90089-1061, USA. · Int Psychogeriatr. · Pubmed #12475088 No free full text.

Abstract: This study examined the utility of the TELE, a telephone assessment for dementia, in a sample of 269 individuals that was not selected on the basis of previous dementia diagnosis. Thus, the conditions of the study reflect the actual situation in which a screening instrument might be employed. Scores on TELE were compared to dementia diagnoses. Using the best cutoff score, sensitivity was .86 and specificity was .90. Longitudinal follow-up established that false positives primarily included those who subsequently developed dementia. Telephone screening for dementia has both clinical and research applications. One recommendation based on our experience is that longitudinal studies should include a telephone interview component for anyone who drops out of the study, to enable characterizing the cognitive status of dropouts.

Hassing LB, Johansson B, Nilsson SE, Berg S, Pedersen NL, Gatz M, McClearn G. · Department of Psychology, Göteborg University, Göteborg, Sweden. · Int Psychogeriatr. · Pubmed #12475085 No free full text.

Abstract: BACKGROUND: The purpose of this study was to examine if Type 2 diabetes mellitus is a risk factor for dementia in very old age, specifically for Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: We evaluated the risk of dementia in relation to Type 2 diabetes using a population-based sample of 702 individuals aged 80 years and older (mean age 83 years). A total of 187 persons received a dementia diagnosis. Thirty-one individuals had a diabetes diagnosis prior to onset of the dementia. RESULTS: Cox proportional hazard analyses, adjusted for age, gender, education, smoking habits, and circulatory diseases, indicated an elevated risk to develop VaD (relative risk = 2.54, 95% confidence interval 1.354.78) in individuals with diabetes mellitus. No association was found between diabetes and AD. CONCLUSION: Type 2 diabetes is selectively related to the different subtypes of dementia. There is no increased risk of AD but more than a twofold risk of VaD in persons with diabetes.