ABSTRACT
A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17-85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility. Surprisingly, when studied at scale, the APOE genotype had negligible impact on cognitive performance. Different cognitive domains had distinct genetic architectures, with one indicating brain region-specific activation of microglia and another with glycogen metabolism. Thus, the molecular and cellular mechanisms underpinning cognition are distinct from dementia risk loci, presenting different targets to slow down age-related cognitive decline. Participants can now be recalled stratified by genotype and cognitive phenotype for natural history and interventional studies of neurodegenerative and other disorders.
Subject(s)
Cognition , Genotype , Humans , Aged , Middle Aged , Aged, 80 and over , Adolescent , Adult , Young Adult , Female , Cohort Studies , Male , Apolipoproteins E/genetics , Aging/genetics , EnglandABSTRACT
The relationship between language and thought is the subject of long-standing debate. One claim states that language facilitates categorization of objects based on a certain feature (e.g. color) through the use of category labels that reduce interference from other, irrelevant features. Therefore, language impairment is expected to affect categorization of items grouped by a single feature (low-dimensional categories, e.g. "Yellow Things") more than categorization of items that share many features (high-dimensional categories, e.g. "Animals"). To test this account, we conducted two behavioral studies with individuals with aphasia and an fMRI experiment with healthy adults. The aphasia studies showed that selective low-dimensional categorization impairment was present in some, but not all, individuals with severe anomia and was not characteristic of aphasia in general. fMRI results revealed little activity in language-responsive brain regions during both low- and high-dimensional categorization; instead, categorization recruited the domain-general multiple-demand network (involved in wide-ranging cognitive tasks). Combined, results demonstrate that the language system is not implicated in object categorization. Instead, selective low-dimensional categorization impairment might be caused by damage to brain regions responsible for cognitive control. Our work adds to the growing evidence of the dissociation between the language system and many cognitive tasks in adults.
Subject(s)
Aphasia , Language , Humans , Adult , Brain/diagnostic imaging , Aphasia/diagnostic imagingABSTRACT
Background: It has recently been proposed that a key motivation for joining groups is the protection from consequences of negative behaviours, such as norm violations. Here we empirically test this claim by investigating whether cooperative decisions and the punishment of associated fairness-based norm violations are different in individuals vs. collectives in economic games. Methods: In the ultimatum game, participants made or received offers that they could reject at a cost to their outcome, a form of social punishment. In the dictator game with third-party punishment, participants made offers to a receiver while being observed by a punisher, or could themselves punish unfair offers. Results: Participants made lower offers when making their decision as part of a group as compared to alone. This difference correlated with participants' overall mean offers: those who were generally less generous were even less so in a group, suggesting that the collective structure was compatible with their intention. Participants were slower when punishing vs not punishing an unfair offer. Importantly here, they were slower when deciding whether to punish or not to punish groups as compared to individuals, only when the offer concerned them directly in second party punishment. Participants thus take more time to punish others, and to make their mind on whether to punish or not when facing a group of proposers. Conclusions: Together, these results show that people behave differently in a group, both in their willingness to share with others and in their punishment of norm violations. This could be explained by the fact that being in a collective structure allows to share responsibility with others, thereby protecting from negative consequences of norm violations.