Age and Verbal Fluency: The Mediating Effect of Speed of Processing

Elgamal, Safa; Roy, Éric; Sharratt, M.

doi:10.5770/cgj.v14i3.17

Cited by 67 publications

(60 citation statements)

References 26 publications

(30 reference statements)

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“…This may reflect the influence of processing speed on fluency performance previously described in the literature. 18 Our analyses lacked power to address genes with small effects affecting tests for which we had only a limited sample size. The lack of test-specific power should also be taken into account when interpreting the lack of association with candidate genes beyond APOE ( DTNBP1, TRIB3 and WDR72 ).…”

Section: Discussionmentioning

confidence: 99%

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GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Ibrahim-Verbaas¹,

Bressler²,

Debette³

et al. 2015

Mol Psychiatry

138

120

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To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429–32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value = 3.12 × 10−8) and in the joint discovery and replication meta-analysis (P-value = 3.28 × 10−9 after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value = 4 × 10−4). The protein encoded by CADM2 is involved in glutamate signaling (P-value = 7.22 × 10−15), gamma-aminobutyric acid (GABA) transport (P-value = 1.36 × 10−11) and neuron cell-cell adhesion (P-value = 1.48 × 10−13). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

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Section: Discussionmentioning

confidence: 99%

“…17,18 There is, for example, debate as to whether processing speed is merely one of the cognitive domains, or whether processing speed has a more unique role as a fundamental process underlying variation in more complex cognitive traits as well as in cognitive aging. 19,20 …”

Section: Introductionmentioning

confidence: 99%

GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Ibrahim-Verbaas¹,

Bressler²,

Debette³

et al. 2015

Mol Psychiatry

138

120

View full text Add to dashboard Cite

show abstract

“…This is presumably because phonemic fluency relies more on executive processes and less on the integrity of language networks (Baldo et al 2006(Baldo et al , 2010. Phonemic fluency is also less likely to decline with age (Elgamal et al 2011, Stolwyk et al 2015. The insensitivity of phonemic fluency performance to aphasia severity and normal aging makes it a particularly sensitive measure of executive functioning in individuals with aphasia.…”

Section: Comparison Across Verbal Fluency Tasksmentioning

confidence: 99%

Comparison of animal, action and phonemic fluency in aphasia

Faroqi‐Shah

Milman

2017

Intl J Lang & Comm Disor

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“…Aging substantially affects the nervous system by altering synaptic transmission/plasticity through increased neuroinflammation (Perry, 2010; Sparkman and Johnson, 2008), modified dendritic spine morphologies (Dumitriu et al, 2010; von Bohlen und Halbach et al, 2006), loss of synaptic proteins (Bahr et al, 1992; Clayton et al, 2002; Sonntag et al, 2000), impaired endomembrane recycling and disrupted calcium homeostasis in synapses (Bezprozvanny and Hiesinger, 2013). In fact, cognitive performance likely starts to decline as early as 55 years of age, even in healthy individuals (Elgamal et al, 2011; Hedden and Gabrieli, 2004). Thus, it is urgent to develop efficient therapeutic interventions for aging-related cognitive decline.…”

Section: Introductionmentioning

confidence: 99%

Rescuing effects of RXR agonist bexarotene on aging-related synapse loss depend on neuronal LRP1

Tachibana

Shinohara

Yamazaki

et al. 2016

Experimental Neurology

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Apolipoprotein E (apoE) plays a critical role in maintaining synaptic integrity by transporting cholesterol to neurons through the low-density lipoprotein receptor related protein-1 (LRP1). Bexarotene, a retinoid X receptor (RXR) agonist, has been reported to have potential beneficial effects on cognition by increasing brain apoE levels and lipidation. To investigate the effects of bexarotene on aging-related synapse loss and the contribution of neuronal LRP1 to the pathway, forebrain neuron-specific LRP1 knockout (nLrp1−/−) and littermate control mice were administered with bexarotene-formulated diet (100 mg/kg/day) or control diet at the age of 20-24 months for 8 weeks. Upon bexarotene treatment, levels of brain apoE and ATP-binding cassette sub-family A member 1 (ABCA1) were significantly increased in both mice. While levels of PSD95, glutamate receptor 1 (GluR1), and N-methyl-D-aspartate receptor NR1 subunit (NR1), which are key postsynaptic proteins that regulate synaptic plasticity, were decreased with aging, they were restored by bexarotene treatment in the brains of control but not nLrp1−/− mice. These results indicate that the beneficial effects of bexarotene on synaptic integrity depend on the presence of neuronal LRP1. However, we also found that bexarotene treatment led to the activation of glial cells, weight loss and hepatomegaly, which are likely due to hepatic failure. Taken together, our results demonstrate that apoE-targeted treatment through the RXR pathway has a potential beneficial effect on synapses during aging; however, the therapeutic application of bexarotene requires extreme caution due to its toxic side effects.

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Age and Verbal Fluency: The Mediating Effect of Speed of Processing

Cited by 67 publications

References 26 publications

GWAS for executive function and processing speed suggests involvement of the CADM2 gene

GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Comparison of animal, action and phonemic fluency in aphasia

Rescuing effects of RXR agonist bexarotene on aging-related synapse loss depend on neuronal LRP1

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