Menopause Status and Within-Group Differences in Chronological Age Affect the Functional Neural Correlates of Spatial Context Memory in Middle-Aged Females.

Reductions in the ability to encode and retrieve past experiences in rich spatial contextual detail (episodic memory) are apparent by midlife-a time when most females experience spontaneous menopause. Yet, little is known about how menopause status affects episodic memory-related brain activity at encoding and retrieval in middle-aged premenopausal and postmenopausal females, and whether any observed group differences in brain activity and memory performance correlate with chronological age within group. We conducted an event-related task fMRI study of episodic memory for spatial context to address this knowledge gap. Multivariate behavioral partial least squares was used to investigate how chronological age and retrieval accuracy correlated with brain activity in 31 premenopausal females (age range, 39.55-53.30 years; mean age, 44.28 years; SD age, 3.12 years) and 41 postmenopausal females (age range, 46.70-65.14 years; mean age, 57.56 years; SD age, 3.93 years). We found that postmenopausal status, and advanced age within postmenopause, was associated with lower spatial context memory. The fMRI analysis showed that only in postmenopausal females, advanced age was correlated with decreased activity in occipitotemporal, parahippocampal, and inferior parietal cortices during encoding and retrieval, and poorer spatial context memory performance. In contrast, only premenopausal females exhibited an overlap in encoding and retrieval activity in angular gyrus, midline cortical regions, and prefrontal cortex, which correlated with better spatial context retrieval accuracy. These results highlight how menopause status and chronological age, nested within menopause group, affect episodic memory and its neural correlates at midlife.SIGNIFICANCE STATEMENT This is the first fMRI study to examine how premenopause and postmenopause status affect the neural correlates of episodic memory encoding and retrieval, and how chronological age contributes to any observed group similarities and differences. We found that both menopause status (endocrine age) and chronological age affect spatial context memory and its neural correlates. Menopause status directly affected the direction of age-related and performance-related correlations with brain activity in inferior parietal, parahippocampal, and occipitotemporal cortices across encoding and retrieval. Moreover, we found that only premenopausal females exhibited cortical reinstatement of encoding-related activity in midline cortical, prefrontal, and angular gyrus, at retrieval. This suggests that spatial context memory abilities may rely on distinct brain systems at premenopause compared with postmenopause.

The adverse effect of modifiable dementia risk factors on cognition amplifies across the adult lifespan.

Background: Reversible lifestyle behaviors (modifiable risk factors) can reduce dementia risk by 40%, but their prevalence and association with cognition throughout the adult lifespan is less well understood. Methods: The associations between the number of modifiable risk factors for dementia (low education, hypertension, hearing loss, traumatic brain injury, alcohol or substance abuse, diabetes, smoking, and depression) and cognition were examined in an online sample (N = 22,117, ages 18-89). Findings: Older adults (ages 66-89) had more risk factors than middle-aged (ages 45-65) and younger adults (ages 18-44). Polynomial regression revealed that each additional risk factor was associated with lower cognitive performance (equivalent to 3 years of aging), with a larger association as age increased. People with no risk factors in their forties to seventies showed similar cognitive performance to people 10 or 20 years younger with many risk factors. Interpretation: Modifiable dementia risk factors amplify lifespan age differences in cognitive performance.

Sex differences and modifiable dementia risk factors synergistically influence memory over the adult lifespan.

Introduction: More women than men develop Alzheimer's disease, yet women perform better and show less decline on episodic memory measures, a contradiction that may be accounted for by modifiable risk factors for dementia. Methods: Associations among age, sex, modifiable dementia risk factors, and cognition were measured in a cross-sectional online sample (n = 21,840, ages 18 to 89). Results: Across four tests of associative memory and executive functions, only a Face-Name Association task revealed sex differences in associative memory that varied by age. Men had worse memory than women (the equivalent of performing similar to someone 4 years older) across ages. Men had larger age differences than women (ie, worse memory in older ages) among people with no to one risk factor, but not those with multiple risk factors. Discussion: Because the relationship between dementia risk factors and age-related memory differences varies between men and women, sex-specific dementia prevention approaches are warranted.

When I'm 64: Age-Related Variability in Over 40,000 Online Cognitive Test Takers.

OBJECTIVES: Age-related differences in cognition are typically assessed by comparing groups of older to younger participants, but little is known about the continuous trajectory of cognitive changes across age, or when a shift to older adulthood occurs. We examined the pattern of mean age differences and variability on episodic memory and executive function measures over the adult life span, in a more fine-grained way than past group or life-span comparisons. METHOD: We used a sample of over 40,000 people aged 18-90 who completed psychometrically validated online tests measuring episodic memory and executive functions (the Cogniciti Brain Health Assessment). RESULTS: Cognitive performance declined gradually over adulthood, and rapidly later in life on spatial working memory, processing speed, facilitation (but not interference), associative recognition, and set shifting. Both polynomial and segmented regression fit the data well, indicating a nonlinear pattern. Segmented regression revealed a shift from gradual to rapid decline that occurred in the early 60s. Variability between people (interindividual variability or diversity) and variability within a person across tasks (intraindividual variability or dispersion) also increased gradually until the 60s, and rapidly after. Confirmatory factor analysis revealed a single general factor (of variance shared between tasks) offered a good fit for performance across tasks. DISCUSSION: Life-span cognitive performance shows a nonlinear pattern, with gradual decline over early and mid-adulthood, followed by a transition in the 60s to notably accelerated, but more variable, decline. Some people show less decline than others, and some cognitive abilities show less within-person decline than others.

Interindividual and intraindividual variability in amnestic mild cognitive impairment (aMCI) measured with an online cognitive assessment.

INTRODUCTION: Mean cognitive performance is worse in amnestic mild cognitive impairment (aMCI) compared to control groups. However, studies on variability of cognitive performance in aMCI have yielded inconclusive results, with many differences in variability measures and samples from one study to another. METHODS: We examined variability in aMCI using an existing older adult sample (n = 91; 51 with aMCI, 40 with normal cognition for age), measured with an online self-administered computerized cognitive assessment (Cogniciti's Brain Health Assessment). Our methodology extended past findings by using pure measures of variability (controlling for confounding effects of group performance or practice), and a clinically representative aMCI sample (reflecting the continuum of cognitive performance between normal cognition and aMCI). RESULTS: Between-group t-tests showed significantly greater between-person variability (interindividual variability or diversity) in overall cognitive performance in aMCI than controls, although the effect size was with a small to moderate effect size, d = 0.44. No significant group differences were found in within-person variability (intraindividual variability) across cognitive tasks (dispersion) or across trials of a response time task (inconsistency), which may be because we used a sample measuring the continuum of cognitive performance. Exploratory correlation analyses showed that a worse overall score was associated with greater inter- and intraindividual variability, and that variability measures were correlated with each other, indicating people with worse cognitive performance were more variable. DISCUSSION: The current study demonstrates that self-administered online tests can be used to remotely assess different types of variability in people at risk of Alzheimer`s. Our findings show small but significantly more interindividual differences in people with aMCI. This diversity is considered as "noise" in standard assessments of mean performance, but offers an interesting and cognitively informative "signal" in itself.