Validation of a Dynamic Measure of Current Cognitive Reserve in a Longitudinally Assessed Sample of Healthy Older Adults: The Tasmanian Healthy Brain Project.

Cognitive reserve (CR) is a theoretical construct describing the underlying cognitive capacity of an individual that confers differential levels of resistance to, and recovery from, brain injuries of various types. To date, estimates of an individual's level of CR have been based on single proxy measures that are retrospective and static in nature. To develop a measure of dynamic change in CR across a lifetime, we previously identified a latent factor, derived from an exploratory factor analysis of a large sample of healthy older adults, as current CR (cCR). In the present study, we examined the longitudinal results of a sample of 272 older adults enrolled in the Tasmanian Healthy Brain Project. Using results from 12-month and 24-month reassessments, we examined the longitudinal validity of the cCR factor using confirmatory factor analyses. The results of these analyses indicate that the cCR factor structure is longitudinally stable. These results, in conjunction with recent results from our group demonstrating dynamic increases in cCR over time in older adults undertaking further education, lend weight to this cCR measure being a valid estimate of dynamic change in CR over time.

Further education improves cognitive reserve and triggers improvement in selective cognitive functions in older adults: The Tasmanian Healthy Brain Project.

INTRODUCTION: The strong link between early-life education and subsequent reduced risk of dementia suggests that education in later life could enhance cognitive function and may reduce age-related cognitive decline and protect against dementia. METHODS: Episodic memory, working memory, executive function, and language processing performances were assessed annually over 4 years in 359 healthy older adults who attended university for a minimum of 12 months (intervention) and were compared against 100 healthy adult controls. RESULTS: Multiple group latent growth curve modeling revealed a significant improvement in language processing capacity over time in the intervention group. No changes were detected for episodic memory, working memory, or executive function. DISCUSSION: These results suggest that complex mental stimulation resulting from late-life further education results in improved crystallized knowledge but no changes to fluid cognitive functions.

The BDNF Val66Met polymorphism moderates the effect of cognitive reserve on 36-month cognitive change in healthy older adults.

INTRODUCTION: Cognitive reserve (CR) and BDNF Val66Met are independently associated with the rate of cognitive decline in preclinical Alzheimer's disease. This study was designed to investigate the interactive effects of these variables on 36-month cognitive change in cognitively intact older adults. METHODS: Data for this investigation were obtained from 445 community-residing participants of the Tasmanian Healthy Brain Project, who underwent genetic screening and annual assessment of neuropsychological, health, and psychosocial function. RESULTS: Our main result was that BDNF Val66Met moderated the relationship between baseline CR and change in executive function performance, in that CR-related differences in function decreased across the follow-up period in BDNF Val homozygotes, but became more pronounced in BDNF Met carriers. Similar effects were not observed within the other memory- and language-related cognitive domains. DISCUSSION: Inheritance of BDNF Met may be associated with a detrimental influence on the relationship between CR and cognitive change in cognitively intact older adults, but this effect may be restricted to the executive function domain.

Variations in the APOE allele or BDNF Val66Met polymorphism are not associated with changes in cognitive function following a tertiary education intervention in older adults: the Tasmanian Healthy Brain Project.

The apolipoprotein (APOE) ε4 allele and the Met variant of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism are associated with reduced cognitive function in older adults. The aim of this study was to examine the independent and interactional effect of the APOE ε4 allele and BDNF Val66Met polymorphism on cognitive function in a cohort of healthy older adults who had undertaken further university level education. Multiple group latent growth curve modeling revealed no change in cognitive function over time in APOE ε4-carriers or in BDNF Met-carriers, nor in carriers of both APOE-ε4 and BDNF-Met alleles. Further, the results indicate that allelic variation in either APOE or BDNF does not modify the beneficial effects of a university-based education intervention on cognitive function over a 4-year period following the intervention.

Age is no barrier: predictors of academic success in older learners.

Although predictors of academic success have been identified in young adults, such predictors are unlikely to translate directly to an older student population, where such information is scarce. The current study aimed to examine cognitive, psychosocial, lifetime, and genetic predictors of university-level academic performance in older adults (50-79 years old). Participants were mostly female (71%) and had a greater than high school education level (M = 14.06 years, SD = 2.76), on average. Two multiple linear regression analyses were conducted. The first examined all potential predictors of grade point average (GPA) in the subset of participants who had volunteered samples for genetic analysis (N = 181). Significant predictors of GPA were then re-examined in a second multiple linear regression using the full sample (N = 329). Our data show that the cognitive domains of episodic memory and language processing, in conjunction with midlife engagement in cognitively stimulating activities, have a role in predicting academic performance as measured by GPA in the first year of study. In contrast, it was determined that age, IQ, gender, working memory, psychosocial factors, and common brain gene polymorphisms linked to brain function, plasticity and degeneration (APOE, BDNF, COMT, KIBRA, SERT) did not influence academic performance. These findings demonstrate that ageing does not impede academic achievement, and that discrete cognitive skills as well as lifetime engagement in cognitively stimulating activities can promote academic success in older adults.

Sending your grandparents to university increases cognitive reserve: The Tasmanian Healthy Brain Project.

OBJECTIVE: Increasing an individual's level of cognitive reserve (CR) has been suggested as a nonpharmacological approach to reducing the risk for Alzheimer's disease. We examined changes in CR in older adults participating over 4 years in the Tasmanian Healthy Brain Project. METHOD: A sample of 459 healthy older adults between 50 and 79 years of age underwent a comprehensive annual assessment of current CR, neuropsychological function, and psychosocial factors over a 4-year period. The intervention group of 359 older adults (M = 59.61 years, SD = 6.67) having completed a minimum of 12 months part-time university study were compared against a control reference group of 100 adults (M = 62.49 years, SD = 6.24) who did not engage in further education. RESULTS: Growth mixture modeling demonstrated that 44.3% of the control sample showed no change in CR, whereas 92.5% of the further education participants displayed a significant linear increase in CR over the 4 years of the study. These results indicate that older adults engaging in high-level mental stimulation display an increase in CR over a 4-year period. CONCLUSION: Increasing mental activity in older adulthood may be a viable strategy to improve cognitive function and offset cognitive decline associated with normal aging. (PsycINFO Database Record

Does the Cambridge Automated Neuropsychological Test Battery (CANTAB) Distinguish Between Cognitive Domains in Healthy Older Adults?

The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a semiautomated computer interface for assessing cognitive function. We examined whether CANTAB tests measured specific cognitive functions, using established neuropsychological tests as a reference point. A sample of 500 healthy older (M = 60.28 years, SD = 6.75) participants in the Tasmanian Healthy Brain Project completed battery of CANTAB subtests and standard paper-based neuropsychological tests. Confirmatory factor analysis identified four factors: processing speed, verbal ability, episodic memory, and working memory. However, CANTAB tests did not consistently load onto the cognitive domain factors derived from traditional measures of the same function. These results indicate that five of the six CANTAB subtests examined did not load onto single cognitive functions. These CANTAB tests may lack the sensitivity to measure discrete cognitive functions in healthy populations or may measure other cognitive domains not included in the traditional neuropsychological battery.

Modeling cognitive reserve in healthy middle-aged and older adults: the Tasmanian Healthy Brain Project.

BACKGROUND: Cognitive reserve (CR) is a protective factor that supports cognition by increasing the resilience of an individual's cognitive function to the deleterious effects of cerebral lesions. A single environmental proxy indicator is often used to estimate CR (e.g. education), possibly resulting in a loss of the accuracy and predictive power of the investigation. Furthermore, while estimates of an individual's prior CR can be made, no operational measure exists to estimate dynamic change in CR resulting from exposure to new life experiences. METHODS: We aimed to develop two latent measures of CR through factor analysis: prior and current, in a sample of 467 healthy older adults. RESULTS: The prior CR measure combined proxy measures traditionally associated with CR, while the current CR measure combined variables that had the potential to reflect dynamic change in CR due to new life experiences. Our main finding was that the analyses uncovered latent variables in hypothesized prior and current models of CR. CONCLUSIONS: The prior CR model supports multivariate estimation of pre-existing CR and may be applied to more accurately estimate CR in the absence of neuropathological data. The current CR model may be applied to evaluate and explore the potential benefits of CR-based interventions prior to dementia onset.

APOE and BDNF Val66Met polymorphisms combine to influence episodic memory function in older adults.

Genetic polymorphisms of apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF) have shown inconsistent associations with healthy adult cognitive functions. Recent investigations have suggested that APOE polymorphisms do not contribute to non-pathological cognitive function and that any effect is likely due to prodromal Alzheimer's disease (AD). Similarly, although BDNF Val66Met polymorphisms affect hippocampal morphology and function, associations with learning and/or memory have not always been found. This study sought to determine whether APOE and BDNF polymorphisms were associated, either independently or in combination, with adult cognition. Comprehensive neuropsychological assessments were conducted on 433 older adults, aged 50-79 years (M=62.16, SD=6.81), which yielded measures of episodic memory, working memory, executive function, and language processing. Participants underwent comprehensive neuropsychological assessment to ensure that only cognitively intact individuals comprised the sample. APOE and BDNF polymorphic data were used as predictors in general linear models that assessed composite cognitive domain variables, while covarying for education and age. Although no main effects for APOE or BDNF were found, the analysis identified a significant APOE×BDNF interaction that predicted episodic memory performance (p=.02, η(2)=.02). Post-hoc analyses demonstrated that in BDNF Val homozygotes, the cognitive consequences of APOE polymorphisms were minimal. However, in BDNF Met carriers, the hypothesized beneficial/detrimental effects of APOE polymorphisms were found. Our data show that concurrent consideration of both APOE and BDNF polymorphisms are required in order to witness a cognitive effect in healthy older adults.

The Tasmanian Healthy Brain Project (THBP): a prospective longitudinal examination of the effect of university-level education in older adults in preventing age-related cognitive decline and reducing the risk of dementia.

BACKGROUND: Differences in the level of cognitive compromise between individuals following brain injury are thought to arise from underlying differences in cognitive reserve. The level of cognitive reserve attained by an individual is influenced by both genetic and life experience factors such as educational attainment and occupational history. The Tasmanian Healthy Brain Project (THBP) is a world-first prospective study examining the capacity of university-level education to enhance cognitive reserve in older adults and subsequently reduce age-related cognitive decline and risk for neurodegenerative disease. METHODS: Up to 1,000 adults aged 50-79 years at the time of entry into the study will be recruited to participate in the THBP. All participants will be healthy and free of significant medical, psychological, or psychiatric illness. Of the participant sample, 90% will undertake a minimum of 12 months part-time university-level study as an intervention. The remaining 10% will act as a control reference group. Participants will complete an annual comprehensive assessment of neuropsychological function, medical health, socialization, and personal well-being. Premorbid estimates of past cognitive, education, occupational, and physical function will be used to account for the mediating influence of prior life experience on outcomes. Potential contributing genetic factors will also be explored. RESULTS: Participant results will be assessed annually. Participants displaying evidence of dementia on the comprehensive neuropsychological assessment will be referred to an independent psycho-geriatrician for screening and diagnosis. CONCLUSIONS: The THBP commenced in 2011 and is expected to run for 10-20 years duration. To date, a total of 383 participants have been recruited into the THBP.

Neuropsychological measures predict decline to Alzheimer's dementia from mild cognitive impairment.

OBJECTIVE: Studies of Mild Cognitive Impairment (MCI) show elevated rates of conversion to dementia at the group level. However, previous studies of the trajectory of MCI identify great heterogeneity of outcomes, with a significant proportion of individuals with MCI remaining stable over time, changing MCI subtype classification, or reverting to a normal cognitive state at long-term follow-up. METHOD: The present study examined individual outcomes at 20 months in a group of older adults classified according to MCI subtypes. A total of 106 participants, 81 with different subtypes of MCI and 25 healthy controls, undertook longitudinal neuropsychological assessment of visual and verbal memory, attentional processing, executive functions, working memory capacity, and semantic memory. RESULTS: At 20 months 12.3% of the MCI group progressed to dementia, 62.9% continued to meet MCI criteria, and 24.7% reverted to unimpaired levels of function. A discriminant function analysis predicted outcome at 20 months on the basis of baseline neuropsychological test performance with 86.3% accuracy. The analysis indicated that a pattern of impairments on visual episodic memory, verbal episodic memory, short-term memory, working memory, and attentional processing differentiated between participants who developed dementia, recovered from MCI, or remained in stable MCI. CONCLUSIONS: The results of the present study raise questions regarding the specificity of existing criteria for the subtypes of MCI, with these results indicating a high degree of instability in classification over time. In addition, the results suggest that multidomain MCI is the most reliable precursor stage to the development of AD.

Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment.

OBJECTIVE: Mild cognitive impairment (MCI) has emerged as a classification for a prodromal phase of cognitive decline that may precede the emergence of Alzheimer's disease (AD). Recent research suggests that attention, executive, and working memory deficits may appear much earlier in the progression of AD than traditionally conceptualized, and may be more consistently associated with the later development of AD than memory processing deficits. The present study longitudinally tracked attention, executive and working memory functions in subtypes of MCI. METHOD: In a longitudinal study, 52 amnestic MCI (a-MCI), 29 nonamnestic MCI (na-MCI), and 25 age- and education-matched controls undertook neuropsychological assessment of visual and verbal memory, attentional processing, executive functioning, working memory capacity, and semantic language at 10 month intervals. RESULTS: Analysis by repeated measures ANOVA indicate that the a-MCI and na-MCI groups displayed a decline in simple sustained attention (ηp² = .054) with a significant decline on a task of divided attention (ηp² = .053) being evident in the a-MCI group. Stable deficits were found on other measures of attention, working memory and executive function in the a-MCI and na-MCI groups. The a-MCI group displayed stable impairments to visual and verbal memory. CONCLUSIONS: The results indicate that a-MCI and na-MCI display a stable pattern of deficits to attention, working memory, and executive function. The decline in simple sustained attention in a-MCI and n-MCI groups and to divided attention in a-MCI may be early indicators of possible transition to dementia from MCI. However, further research is required to determine this.

Attention and working memory deficits in mild cognitive impairment.

Mild cognitive impairment (MCI) has emerged as a classification for a prodromal phase of cognitive decline preceding the emergence of Alzheimer's disease (AD). We examined neuropsychological functioning in a sample of 60 adults with amnestic-MCI (a-MCI), 32 with subjective complaints of memory impairment (subjective-MCI, s-MCI), 14 with mild AD, and 25 age-matched controls. Both the a-MCI and s-MCI groups displayed impaired attentional processing, working memory capacity, and semantic language, with a-MCI displaying additional impairments to verbal and/or visual memory. These results indicate that further research is needed to examine cognitive decline in nonamnestic variants of MCI.