The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, 1983 through 2003

Rabbitt, Patrick; McInnes, Lynn; Diggle, P.; Holland, Fiona; Bent, Nuala; Abson, Vicki; Pendleton, Neil; Horan, Mike

doi:10.1080/13825580490511116

Cited by 121 publications

(103 citation statements)

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“…We estimated group averages (fixed effects) for each change parameter; however, estimates of individual variations (random effects) were limited to intercepts and linear slopes due to non-convergence of models with quadratic change as a random effect. Previously published MLSC analyses confirmed the presence of retest effects (Ghisletta et al, 2012;Rabbitt et al, 2004Rabbitt et al, , 2011. We therefore estimated cognitive change both with and without adjusting for retest effects.…”

Section: Preparatory Analysesmentioning

confidence: 73%

Life span decrements in fluid intelligence and processing speed predict mortality risk.

Aichele

Rabbitt

Ghisletta

2015

Psychology and Aging

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We examined lifespan changes in five domains of cognitive performance as predictive of mortality risk. Data came from the Manchester Longitudinal Study of Cognition, a 20-plus year investigation of 6203 individuals aged 42-97 years. Cognitive domains included crystallized intelligence, fluid intelligence, verbal memory, visual memory, and processing speed. Lifespan decrements were evident across these domains, controlling for baseline performance at age 70 and adjusting for retest effects. Survival analyses stratified by sex and conducted independently by cognitive domain showed that lower baseline performance levels in all domains-and larger lifespan decrements in fluid intelligence and processing speed-were predictive of increased mortality risk for both females and males. Critically, analyses of the combined predictive power of cognitive performance variables showed that baseline levels of processing speed (in females) and fluid intelligence (in males), and decrements in processing speed (in females and in males) and fluid intelligence (in females), accounted for most of the explained variation in mortality risk. In light of recent evidence from brain imaging studies, we speculate that cognitive abilities closely linked to cerebral white matter integrity (such as processing speed and fluid intelligence) may represent particularly sensitive markers of mortality risk. Additionally, we presume that greater complexity in cognition-survival associations observed in females (in analyses incorporating all cognitive predictors) may be a consequence of longer and more variable cognitive declines in females relative to males. KEYWORDS: cognition, survival, aging, processing speed, fluid intelligence

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Section: Preparatory Analysesmentioning

confidence: 73%

Life span decrements in fluid intelligence and processing speed predict mortality risk.

Aichele

Rabbitt

Ghisletta

2015

Psychology and Aging

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“…As vocabulary ability tends to remain relatively stable with age, longitudinal analysis was not performed on the MHA test. 40 Data were adjusted for age and gender by covarying their effects. The comorbid medical disorders of hypertension, diabetes and depression were investigated as potential confounders.…”

Section: Discussionmentioning

confidence: 99%

“…Previous work by our group has shown that tests of fluid intelligence decline at a faster and accelerated rate in normal elderly individuals compared to memory tests, which declined at a slower and linear rate. 40 In addition, work using mouse models has found that serotonin levels in aged mice are depleted to a greater extent in the cortex (implicated in fluid intelligence) (25% reduction) than the hippocampus (involved in memory) (16% reduction). 46 It is therefore likely that the VNTR2 polymorphism has a stronger association with tests of Influence of serotonin transporter gene polymorphisms A Payton et al fluid intelligence because they have a steeper trajectory with greater interindividual variation (which subsequently increases statistical power) and because preferential depletion of serotonin in the frontal cortex further reduces the amount of serotonin available for receptor binding.…”

Section: Discussionmentioning

confidence: 99%

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Influence of serotonin transporter gene polymorphisms on cognitive decline and cognitive abilities in a nondemented elderly population

et al. 2005

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Dysfunction of the serotonergic pathway disrupts normal cognitive functioning and is believed to be the underlying basis for a variety of psychiatric disorders. Two functional polymorphisms within the serotonin transporter (SLC6A4) gene (promoter 44 bp insertion/deletion (HTTLPR) and an intron two 16 or 17 bp variable number tandem repeat (VNTR2)) have been extensively studied in psychiatric conditions but not in the cognitive functioning of normal individuals. We have investigated these two polymorphisms for association with both the level of cognitive abilities and their decline with age using a cohort consisting of over 750 elderly nondemented individuals with a follow-up of up to 15 years. We found that volunteers homozygous for the VNTR2 12 allele had a faster rate of decline for all cognitive tests. This reached significance for both tests of fluid intelligence (novel problem solving) (AH1 P ¼ 0.002, AH2 P ¼ 0.014), the test of semantic memory (P ¼ 0.010) and general cognitive ability (P ¼ 0.006). No association was observed between the HTTLPR polymorphism and the rate of cognitive decline when analysed either independently or in combination with the VNTR2 polymorphism based on their influence on expression in vitro. No associations were observed between the two polymorphisms and the baseline level of cognitive abilities. This is only the second gene that has been reported to regulate the rate of cognitive decline in nondemented individuals and may be a target for the treatment of cognitive impairment in the elderly. Keywords: serotonin transporter; polymorphism; cognition; memory; genes; associationIn an increasingly long-lived population severe cognitive impairment, caused by either the normal ageing process or dementia, is an escalating problem that currently has no effective treatment. Cognitive ability and its rate of decline are highly heritable and both have been shown to predict dementia onset. [1][2][3][4] Of the 13 quantitative trait loci (QTL) currently associated with the level of cognitive ability in normal individuals the most widely reported are located in genes involved in synaptic transmission. 5 These comprise the adrenergic receptor 2A, catechol-O-methyltransferase, dopamine receptor D2, cholinergic muscarinic 2 receptor, brain-derived neurotrophic factor, metabotrophic glutamate receptor 3 and the serotonin receptor 2A. [6][7][8][9][10][11][12][13] To date only the apolipoprotein E e4 allele has been associated with cognitive decline in nondemented individuals and this finding has been challenged. [14][15][16][17][18][19] Serotonin has been shown to play a role in brain development and cognitive functioning. 20,21 There is also a decrease in total brain serotonin with age that may predispose the elderly to depression, dementia and cognitive dysfunction. 22 Despite the importance of serotonin as a modulator of memory and learning the influence of two functional polymorphisms (HTTLPR and VNTR2) in the SLC6A4 gene, which codes for a protein responsible for the reuptake of serotonin, have n...

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“…We sought replication in newly available genome-wide association genotype data from cohorts of older individuals from England and Scotland in the Cognitive Ageing Genetics in England and Scotland (CAGES) consortium: the Lothian Birth Cohort of 1921 (LBC1921), 19 the Aberdeen Birth Cohort of 1936 (ABC1936) 19,20 and the Manchester and Newcastle Longitudinal Studies of Cognitive Ageing. 21 …”

Section: Introductionmentioning

confidence: 99%

Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

et al. 2011

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Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P¼0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities.

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The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, 1983 through 2003

Cited by 121 publications

References 1 publication

Life span decrements in fluid intelligence and processing speed predict mortality risk.

Life span decrements in fluid intelligence and processing speed predict mortality risk.

Influence of serotonin transporter gene polymorphisms on cognitive decline and cognitive abilities in a nondemented elderly population

Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

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