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People with type 2 diabetes are at increased risk of age-related cognitive impairment. Previous literature has focused on case-control studies comparing rates of cognitive impairment in patients with and without diabetes. Investigations of potential risk factors for cognitive impairment (including those with increased prevalence in diabetes, such as macrovascular disease, and diabetes-specific factors such as hypoglycaemia) in study populations consisting exclusively of patients with type 2 diabetes have been largely neglected. Moreover, previous studies have failed to take advantage of the extensive characterisation and prospective nature of longitudinal cohort studies to investigate the relative predictive ability of a wider range of potential risk factors for cognitive decline. Using data from the prospective Edinburgh Type 2 Diabetes Study (ET2DS) the present thesis aimed (i) to determine associations of cognitive decline with macrovascular disease and with severe hypoglycaemia, and (ii) to compare a wider range of potential risk factors in their ability to predict cognitive decline. In 2006/2007, 1066 patients with type 2 diabetes (aged 60 to 75 years) attended the baseline ET2DS clinic and 831 returned for the follow-up at year 4. Subjects were extensively characterised for risk factor profiles at baseline, and at year 4 for incidence of severe hypoglycaemia. Socioeconomic status was estimated using postcode data. Scores on seven tests of age-sensitive ‘fluid’ cognitive function, which were administered at baseline and at year 4, were used to derive a general cognitive component (‘g’). A vocabulary-based test, administered at baseline, estimated pre-morbid ability. Findings are reported in three parts. 1.) Macrovascular disease and cognition: Subjects with higher levels of biomarkers indicative of subclinical macrovascular disease, including plasma N-terminal pro-brain natriuretic peptide and carotid intima-media thickness, had significantly steeper four-year cognitive decline, independent of traditional cardiovascular risk factors, stroke, socioeconomic status and estimated pre-morbid cognitive ability. For ankle-brachial pressure index, the association fell just short of statistical significance. Effect sizes were overall modest, with fully adjusted standardised beta coefficients ranging from 0.06 to -0.12. Little evidence was found for associations of the symptomatic markers of macrovascular disease with four-year change in cognitive function that was independent of participants’ pre-morbid ability and socioeconomic status. 2.) Severe hypoglycaemia and cognition: Subjects with lower cognitive ability at baseline were at two-fold increased risk of experiencing their first-ever incident severe hypoglycaemia during follow-up. The rate of four-year cognitive decline was significantly steeper in those exposed to hypoglycaemia compared with hypoglycaemia-free participants, independently of cardiovascular risk factors, microand macrovascular disease and of estimated pre-morbid cognitive ability. Effect sizes again were overall modest (Cohen’s d = 0.2 to 0.3 for statistically significant differences in four-year cognitive decline between subjects with and those without hypoglycaemia, following multivariable adjustment) 3.) Consideration of a wider range of risk factors and cognition: A stepwise linear regression model including a total of 15 metabolic and vascular risk factors identified inflammation, smoking and poorer glycaemic control (in addition to some of the subclinical markers of macrovascular disease) as predictive of a steeper four-year cognitive decline. Other traditional cardiovascular risk factors, diabetic retinopathy, clinical macrovascular disease and a baseline history of severe hypoglycaemia were not included in this model. The interpretation of the latter finding is limited, however, by the fact that the stepwise regression procedure may exclude true predictors from a model when they correlate with already included risk factors. This thesis has demonstrated associations of later-life cognitive decline in people with type 2 diabetes with markers of subclinical macrovascular disease and poor glycaemic control (including hypoglycaemia) as well as other cardiometabolic risk factors (inflammation, smoking). Findings suggest that associations are relatively weak and complex due to inter-relationships amongst risk factors, and indicate a role of pre-morbid ability and socioeconomic status (which as risk factors are difficult to modify) in the relationships of risk factors with cognitive decline. Future research including case-control studies to compare risk factor associations between people with type 2 diabetes and non-diabetic older adults and randomised controlled trials to evaluate potential causal effects of individual modifiable risk factors on cognitive decline, will help to evaluate the mechanisms underlying the observation that people with type 2 diabetes are at risk of cognitive impairment in later life.

Accurate memory for an object or event requires that multiple diverse features are bound together and retained as an integrated representation. There is overwhelming evidence that healthy ageing is accompanied by an associative deficit in that older adults struggle to remember relations between items above any deficit exhibited in remembering the items themselves. However, the effect of age on the ability to bind features within novel objects (for example, their colour and shape) and retain correct conjunctions over brief intervals is less clear. The relatively small body of work that exists on this topic to-date has suggested no additional working memory impairment for conjunctions of features beyond a general age-related impairment in the ability to temporarily retain features. This is in stark contrast to the feature binding deficit observed in the early stages of Alzheimer’s disease. Nevertheless, there have been reports of age-related feature binding deficits in working memory under specific circumstances. Thus a major focus of the present work was to assess these potential boundary conditions. The change detection paradigm was used throughout this work to examine age-differences in visual working memory. Despite the popularity of this task important issues regarding the way in which working memory is probed have been left unaddressed. Chapter 2 reports three experiments with younger adults comparing two methods of testing recognition memory for features or conjunctions. Contrary to an influential study in the field, it appears that processing multiple items at test does not differentially impact on participants’ ability to detect binding changes. Chapters 3, 4, and 5 report a series of experiments motivated by previous findings of specific age-related feature binding deficits. These experiments, improving on previous methodology where possible, demonstrate that increasing the amount of time for which items can be studied (Chapter 3) or mixing feature-conjunction changes in trial-blocks with more salient changes to individual features (Chapters 4 and 5) does not differentially impact on healthy older adults’ ability to detect binding changes. Rather, the argument is made that specific procedural aspects of previous work led to the appearance of deficits that do not generalise. Chapter 5 also addresses the suggestion that healthy ageing specifically affects the retention of item-location conjunctions. The existing evidence for this claim is reviewed, and found wanting, and new data are presented providing evidence against it. To follow-up on the absence of a deficit for simple feature conjunctions, Chapter 6 contrasts two theoretically distinct binding mechanisms: one for features intrinsic to an object and another for extrinsic, contextual features. Preliminary evidence is reported that the cost associated with retaining pairings of features is specifically pronounced for older adults when the features are extrinsic to each other. In an attempt to separate out the contribution of working memory capacity and lapses of attention to age-differences in overall task performance, Chapter 7 reports the results of an exploratory analysis using processing models developed in Chapter 2. Analysis of two data sets from Chapters 4 and 5 demonstrates that lapses of attention make an important contribution to differences in change detection performance. Chapter 8 returns to the issue of measurement in assessing the evidence for specific age-related deficits. Simulations demonstrate that the choice of outcome measure can greatly affect conclusions regarding age-group by condition interactions, suggesting that some previous findings of such interactions in the literature may have been more apparent than real. In closing the General Discussion relates the present work to current theory regarding feature binding in visual working memory and to the wider literature on binding deficits in healthy and pathological ageing.

Many items encoded into episodic memory are highly similar – seeing a stranger’s car may result in a memory representation which overlaps in many features with the memory of your friend’s car. To avoid falsely recognising the novel but similar car, it is important for the representations to be distinguished in memory. Even in healthy young adults failures of this mnemonic discrimination lead relatively often to false recognition, and such errors become substantially more frequent in older age. Whether an item’s representation is discriminated from similar memory representations depends critically on how it is encoded. However, the precise encoding mechanisms involved remain poorly understood. Establishing the determinants of successful mnemonic discrimination is essential for future research into strategies or interventions to prevent recognition errors, particularly in the context of age-related decline. A fuller understanding of age-related decline in mnemonic discrimination can also inform basic models of memory. This thesis evaluated the contribution of encoding processes to mnemonic discrimination both in young adults and in ageing, within the framework of two prominent accounts of recognition memory, the pattern separation account (Wilson et al., 2006) and Fuzzy Trace Theory (FTT; Brainerd & Reyna, 2002). Firstly, a functional magnetic resonance imaging study in young adults found evidence for differences in regions engaged at encoding of images according to the accuracy of later mnemonic discrimination, consistent with both pattern separation and FTT. Evidence of functional overlap between regions showing activity consistent with pattern separation, and activity associated with later accurate recognition was consistent with a role of cortical pattern separation in successful encoding, but there was no direct evidence that cortical pattern separation contributed to mnemonic discrimination. This first evidence of cortical pattern separation in humans was supported by findings that in the majority of pattern separation regions, response functions to stimuli varied in their similarity to previous items were consistent with predictions of computational models. Regional variation in the dimension(s) of similarity (conceptual/perceptual) driving pattern separation was indicative of variation in the type of mnemonic interference minimised by cortical pattern separation. Further evidence of encoding contributions to mnemonic discrimination was provided by an event-related potential study in young and older adults. Older adults showed less distinct waveforms than young adults at encoding of items whose similar lures were later correctly rejected compared to those falsely recognised, supporting the proposal that age-related encoding impairments contribute to the decline in mnemonic discrimination. Finally, a set of behavioural studies found that older adults’ mnemonic discrimination deficit is increased by conceptual similarity, supporting previous findings and consistent with FTT’s account of greater emphasis by older adults on gist processing. However, older adults required greater reduction in perceptual or conceptual similarity in order to successfully reject lures, as uniquely predicted by the pattern separation account. Together, the findings support the notion that encoding processes contribute directly to mnemonic discrimination and its age-related decline. An integrated view of the pattern separation account and FTT is discussed and developed in relation to the current findings.

Goal maintenance is the ability to keep task rules active in-mind so that they can guide behaviour. When this process fails, individuals are unable to use task rules appropriately, and consequently perform poorly on the given task. The rate of goal neglect has been shown to increase with the complexity of the information to be maintained, especially for those with low levels of fluid intelligence. The main aim of this thesis was to examine whether this effect arises from the limited capacity for task rules, the limited ability to cope with competition between task rules, or the limited ability to sustain maintenance of a rule over time both in younger and older adults. A second aim was to investigate whether fluid intelligence and processing speed contribute to performance when goal maintenance is taxed. In particular, the number of instructions presented at the start of the task (Experiments 1-4), the speed at which rules had to be used (Experiment 5), the infrequency with which a task-relevant goal was used relative to a task-irrelevant goal (Experiment 6), and the duration for which rules had to be maintained (Experiment 7) were manipulated. Finally, the importance of goal maintenance in a more real-world setting was examined by testing the relationship between goal neglect and academic performance in children (Experiments 8 and 9). Goal maintenance was not limited by the number of rules to be held in mind, but goal neglect did increase as the degree of competition between rules and the duration with which they were maintained increased. Fluid intelligence accounted for little of the variation in goal maintenance abilities, but processing speed played a moderating role in older adults. In terms of academic performance, goal maintenance in school-aged children significantly predicted mathematics abilities, but not language.

The posterior parietal cortex (PPC) has been reliably implicated in visuospatial attention, such that the dorsal regions (dPPC) are associated with voluntary ‘top-down’ attention, whereas the ventral regions (vPPC) are associated with automatic ‘bottom-up’ attentional processes. The Attention-to-Memory model (AtoM: Ciaramelli, Grady, & Moscovitch, 2008) has suggested that it also plays a similar role in memory retrieval, suggesting that the PPC mediates a domain-general attentional process. Furthermore, domain-generality of attentional processes may account for differences in perception and memory function accompanying old age. This study examined domain-generality by determining the shared variance in performance of tasks thought to recruit top-down and bottom-up attentional processes mediated across both domains. Results clearly suggested generality across domains in top-down processing; and in bottom-up processing, depending on its operationalization. Ageing was characterized by an absence of shared variance across domains and slower reaction times during bottom-up attentional reorienting only in perception.

The posterior parietal cortex (PPC) has been reliably implicated in visuospatial attention, such that the dorsal regions (dPPC) are associated with voluntary ‘top-down’ attention, whereas the ventral regions (vPPC) are associated with automatic ‘bottom-up’ attentional processes. The Attention-to-Memory model (AtoM: Ciaramelli, Grady, & Moscovitch, 2008) has suggested that it also plays a similar role in memory retrieval, suggesting that the PPC mediates a domain-general attentional process. Furthermore, domain-generality of attentional processes may account for differences in perception and memory function accompanying old age. This study examined domain-generality by determining the shared variance in performance of tasks thought to recruit top-down and bottom-up attentional processes mediated across both domains. Results clearly suggested generality across domains in top-down processing; and in bottom-up processing, depending on its operationalization. Ageing was characterized by an absence of shared variance across domains and slower reaction times during bottom-up attentional reorienting only in perception.

This thesis explored two main research questions, firstly investigating whether musical expertise offers a performance advantage in working memory for sequences of tones that vary in pitch, and secondly whether any advantage of musical expertise may be present in older as well as younger individuals. Previous research on working memory for tone sequences has reported that articulatory suppression interferes with temporary storage of verbal but not with tone sequences (Koelsch et al, 2009), suggesting a “tonal loop” within a musician’s working memory (Schulze, Zysset, Mueller, Friederici, & Koelsch, 2011) that complements the phonological loop for verbal material in musicians and non-musicians alike (e.g., Baddeley, 1986; 1992). The five experiments reported here explored detection of a pitch change between pairs of tone sequences with or without concurrent articulatory suppression or singing suppression. In Experiment 1, with pairs of auditory tonal (in a musical key) sequences to be compared, singing suppression impaired non-musicians significantly more than musicians, although both groups showed an impairment, whereas only non-musicians were affected by verbal articulatory suppression. In Experiment 2, conducted only with musicians who could read music, the first sequence of each pair was presented visually and the second sequence for comparison was presented aurally. Musicians were again impaired by singing suppression but not by articulatory suppression. For Experiment 3, for auditory atonal (no musical key) pairs of sequences, non-musicians performed at floor, and musicians were again significantly more impaired by singing suppression than by articulatory suppression. In contrast, for Experiment 4, only with musicians who could read music, for visually presented atonal sequences each followed by an auditory atonal sequence for comparison, musicians were significantly more impaired by articulatory suppression than singing suppression. These results suggest that for tonal sequences, musicians use their musical training and experience, coupled with subvocalised singing, but for atonal sequences, additional strategies involving phonological rehearsal may be used. Non-musicians may also rely on musical experience and subvocal singing for tonal sequences but seem to be unable to do so for atonal sequences. Results are consistent with the use by both musicians and non-musicians of a tonal loop for the rehearsal of tone sequences, which develops with musical training and may be used in addition to subvocal rehearsal. Previous research has suggested musical expertise may offer some protection against cognitive ageing (Hanna-Pladdy & MacKay, 2011; Amer, Kalender, Hasher, Trehub, & Wong, 2013). Experiment 5 in this thesis explored whether a lifetime of musical training and experience may offer the same advantages in old age for retaining tone sequences that had been found in Experiments 1 and 3 for younger musicians. This experiment also considered whether any advantage for older musicians on this task could be explained by the proposed “bilingual advantage” (e.g., Bialystok, Craik, Klein & Viswanathan, 2004), and what other aspects of cognition might be associated with tone sequence memory performance. A test battery was utilised with 74 older adults (60-80 years of age) to assess the influence of musical and language expertise, and cognitive abilities (attention, working memory capacity, self-reported prospective and retrospective memory) on the music-related pitch sequence comparison task from Experiments 1 and 3. Working memory capacity was found to predict individual differences in the ability to detect pitch changes between pairs of tone sequences, regardless of musical experience. Older musicians performed more poorly on the pitch change detection task overall than the younger musicians in the earlier experiments, but their performance on the task was significantly better than for age-matched non-musically trained peers who were close to floor for both tonal and atonal sequences, suggesting some benefit from a lifetime of musical experience.

With an increase in life expectancy, the number of older people affected by cognitive decline and dementia is rising, causing major, global public health concerns. However, there is substantial variation in the rate and magnitude of cognitive decline experienced among ageing individuals. Evidence suggests that many age-associated changes in cognitive functioning can be explained by modifiable lifestyle factors such as smoking, physical activity and diet choices. The weight of the evidence supports the promotion of a healthy lifestyle as an effective strategy for healthy cognitive ageing. Many epidemiological studies have drawn causal conclusions with regard to the positive and direct benefits of lifestyle, yet few have considered the possible confounding role of prior cognitive ability in explaining the lifestyle and cognition relationship in older age. Given the potential for reverse causation, whereby better prior cognitive functioning leads to a greater uptake of healthy behaviours rather than vice versa, it is a mechanism which should be studied, but rarely is. The present thesis focuses on the possible confounding effect of prior cognitive ability on the cross-sectional relationships between lifestyle factors and cognitive ability domains in later-life. The core of the thesis is a series of independent, peer-reviewed (six first-author and one co-author) journal articles in the public domain. Data were derived from the Lothian Birth Cohort 1936 study (n = 1091), a sample of relatively healthy, community-dwelling men and women aged 70 years from Edinburgh, Scotland, for whom childhood (age 11) mental test scores are available. The lifestyle factors investigated were caffeine consumption, alcohol consumption, dietary patterns, body mass index, smoking, serum cholesterol, and physical activity. Cognitive function was assessed across five major ageing-related domains: age 70 IQ (based on the same test that was taken in childhood), general cognitive ability (g), processing speed, memory, and verbal ability. General linear models (ANCOVA) were adjusted for the following covariates: age; sex; childhood cognitive ability; and socioeconomic status (SES). Other potential covariates were additionally adjusted for as necessary. Overall, the positive and significant associations observed between ‘healthy’ lifestyle factors and better cognitive functions at age 70 were consistent with previous research; their effect size was around 1% of the variance in cognitive tests scores. However, these relationships were markedly attenuated (by on average 80%) by a higher childhood cognitive ability and adult SES; for the most part, associations were reduced to non-significance. None of the lifestyle factors were consistent predictors of performance across cognitive domains, though smoking avoidance, a physically active lifestyle, and moderate intake of alcohol, appeared to have the most potential. The key novel finding of this thesis is that, in addition to having predictive value for lifestyle choices over 60 years later, cognitive ability at age 11 accounted for the majority of the cross-sectional associations between lifestyle factors and cognitive abilities in later-life. This finding is consistent with the theory of confounding or even reverse causation. That is, individuals with higher lifetime ‘trait’ cognitive ability may be more likely to adopt a lifestyle which protects against cognitive decline. Rather than a unidirectional or indirect effect of health behaviours on cognitive function, the present findings suggest there may be a dynamic cycle involving cognition, self-management of health and ultimate cognitive outcomes.