Contributions of hippocampal subfields and subregions to episodic memory performance in healthy cognitive aging.

In the present study we investigated whether hippocampal subfield (cornu ammonis 1-3, dentate gyrus, and subiculum) and anteroposterior hippocampal subregion (head,body, and tail) volumes can predict episodic memory function using high-field high resolution structural magnetic resonance imaging (MRI). We recruited 126 healthy participants (18-85 years). MRI datasets were collected on a 4.7 T system. Participants were administered the Wechsler Memory Scale (WMS-IV) to evaluate episodic memory function. Structural equation modeling was used to test the relationship between studied variables. We found that the volume of the dentate gyrus subfield and posterior hippocampus (body) showed a significant direct effect on visuospatial memory performance; additionally, an indirect effect of age on visuospatial memory mediated through these hippocampal subfield/subregion was significant. Logical and verbal memory were not significantly associated with hippocampal subfield or subregion volumes.

Dajianzhong decoction ameliorated D-gal-induced cognitive aging by triggering mitophagy in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Dajianzhong decoction (DJZ) is a classical famous formula for treating yang-deficiency-syndrome in traditional Chinese medicine and recorded in Jin-Kui-Yao-Lue in Dynasty of Dong Han. Cognitive aging can present similar features of mitochondrial energy deficits to the clinical features of Yang deficiency. However, there is poor understanding of the effects of DJZ treatment on mitophagy in cognitive aging. AIM OF THE STUDY: The aims of this work were to decipher the effectiveness and mechanism of DJZ against cognitive aging, focusing on mitophagy. MATERIALS AND METHODS: YFP-Parkin HeLa cells, D-galactose (D-gal) -induced mice (500 mg/kg for 35 d, s. c.) and SH-SY5Y cells (80 mg/ml for 6 h) were established. Firstly, the formation of YFP-Parkin puncta (a well-known mitophagy marker) in YFP-Parkin HeLa cells was employed to discover the mitophagy induction of DJZ. Moreover, the genes and proteins related to PINK1/Parkin pathway and mitochondrial functions were evaluated after treatment with DJZ in vivo (3.5 g/kg or 1.75 g/kg, i. g, 35 d) and in vitro (0.2, 2 and 20 µg/ml, 12 h). Furthermore, the effectiveness of DJZ (3.5 g/kg or 1.75 g/kg, i. g) for alleviating cognitive aging and nerve damage was measured in D-gal mice. Finally, siPINK1 was applied to reverse validation of DJZ in vitro. RESULTS: The formation of YFP-Parkin puncta in YFP-Parkin HeLa cells was markedly induced by DJZ in a dose-dependent manner. The immunofluorescence intensity of Parkin and the protein expression of Parkin in mitochondrial membrane in D-gal mice were significantly increased after treatment of DJZ. The inhibition of PINK1/Parkin pathway in D-gal-induced mice and SH-SY5Y cells was significantly activated by DJZ. Simultaneously, the impairment of mitochondrial functions induced by D-gal were markedly reversed by DJZ. In addition, DJZ significantly ameliorated the neuropathological injury and cognitive declines in D-gal mice. Finally, after PINK1 was knocked down by siPINK1 in vitro, the neuroprotective effects of DJZ and the Parkin enhancement effect of DJZ were markedly reversed. CONCLUSION: Our findings firstly showed DJZ could relieve cognitive aging through facilitating PINK1/Parkin-mediated mitophagy to protect against mitochondrial functions, indicating DJZ may be regarded as a promising intervention in cognitive aging.

Functional alterations of the prefrontal circuit underlying cognitive aging in mice.

Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive function remains unclear. Using calcium imaging and optogenetic manipulation during memory-guided behavior, we show that working-memory coding and the relevant recurrent connectivity in the mouse medial prefrontal cortex (mPFC) are altered as early as middle age. Population activity in the young adult mPFC exhibits dissociable yet overlapping patterns between tactile and auditory modalities, enabling crossmodal memory coding concurrent with modality-dependent coding. In middle age, however, crossmodal coding remarkably diminishes while modality-dependent coding persists, and both types of coding decay in advanced age. Resting-state functional connectivity, especially among memory-coding neurons, decreases already in middle age, suggesting deteriorated recurrent circuits for memory maintenance. Optogenetic inactivation reveals that the middle-aged mPFC exhibits heightened vulnerability to perturbations. These findings elucidate functional alterations of the prefrontal circuit that unfold in middle age and deteriorate further as a hallmark of cognitive aging.

Attitudes toward dementia and cognitive aging among Syrian refugees resettled in Jordan: a qualitative study.

BACKGROUND: Mounting evidence is revealing disparities in cognitive function and heightened dementia risk among refugees, yet research in this area remains scant. Despite bearing most of the world's refugee burden, limited-resource countries like Jordan are facing challenges when dealing with refugee health. There is a lack of research on the attitudes toward dementia and the cognitive healthcare gaps among refugees in Jordan. METHODS: 32 older (≥ 55 years) Syrian refugees resettled in Jordan were recruited through a local community-based organization and interviewed in four focus groups (2 female and 2 male groups). Interviews were transcribed and translated, then coded using inductive thematic analysis. RESULTS: Mean age of the sample was 60.1 years and 53.1% were female. Only 34.4% rated their memory as good or excellent. Themes were organized using the socioecological model: 1) At the individual level, participants believed high levels of stress, including low socioeconomic status, poor health, and traumatic history from their refugee experience increased their dementia risk. 2) Interpersonally, there is a fear of dementia due to the possible impact and burden on loved ones, particularly with the stigma surrounding dementia. 3) At the community level, participants noted that resettlement in Jordan - with a shared language, religion, and culture - offered protective effects due to facilitated access to social connection, information, and mental health self-care. 4) At the institution and policy level, participants believed older refugees faced restrictive policies for economic aid, healthcare, and employment, presenting a significant barrier to healthy aging. CONCLUSIONS: Findings from this study are the first to examine the attitudes of Syrian refugees in Jordan toward dementia and cognitive aging. These results could provide essential data inclusive of refugees as Jordan develops its National Dementia Plan. Investing in dementia awareness interventions and age-friendly neighborhoods may benefit aging refugees in limited-resources settings.

Early Intervention in Cognitive Aging with Strawberry Supplementation.

Late-life dementia is a growing public health concern lacking effective treatment. Neurodegenerative disorders such as Alzheimer's disease (AD) develop over a preclinical period of many years beginning in midlife. The prevalence of insulin resistance, a prominent risk factor for late-life dementia, also accelerates in middle-age. Consumption of berry fruits, including strawberries, has been shown to influence metabolism as well as cognitive performance suggesting potential to mitigate risk for dementia. In this controlled trial, we enrolled overweight middle-aged men and women with insulin resistance and subjective cognitive decline and performed a 12-week intervention with daily administration of whole-fruit strawberry powder. Diet records showed that participants in both groups maintained the prescribed abstinence from berry product consumption outside the study. We observed diminished memory interference (p = 0.02; Cohen's f = 0.45) and a reduction of depressive symptoms (p = 0.04; Cohen's f = 0.39) for the strawberry-treated participants; benefits consistent with improved executive ability. However, there was no effect of the intervention on metabolic measures, possibly a consequence of the sample size, length of the intervention, or comparatively low anthocyanin dose. Anti-inflammatory actions of anthocyanins were considered as a primary mechanistic factor. The findings support the notion that strawberry supplementation has a role in dementia risk reduction when introduced in midlife. However, further investigation with longer intervention periods, larger samples, and differing dosing regimens will be required to assess the benefits of strawberry intake with respect to cognition and metabolic function in the context of aging.

Investigation into Molecular Brain Aging in Senescence-Accelerated Mouse (SAM) Model Employing Whole Transcriptomic Analysis in Search of Potential Molecular Targets for Therapeutic Interventions.

With the progression of an aging society, cognitive aging has emerged as a pressing concern necessitating attention. The senescence-accelerated mouse-prone 8 (SAMP8) model has proven instrumental in investigating the early stages of cognitive aging. Through an extensive examination of molecular changes in the brain cortex, utilizing integrated whole-genome transcriptomics, our principal aim was to uncover potential molecular targets with therapeutic applications and relevance to drug screening. Our investigation encompassed four distinct conditions, comparing the same strain at different time points (1 year vs. 16 weeks) and the same time point across different strains (SAMP8 vs. SAMR1), namely: physiological aging, accelerated aging, early events in accelerated aging, and late events in accelerated aging. Focusing on key functional alterations associated with aging in the brain, including neurogenesis, synapse dynamics, neurometabolism, and neuroinflammation, we identified candidate genes linked to these processes. Furthermore, employing protein-protein interaction (PPI) analysis, we identified pivotal hub genes involved in interactions within these functional domains. Additionally, gene-set perturbation analysis allowed us to uncover potential upstream genes or transcription factors that exhibited activation or inhibition across the four conditions. In summary, our comprehensive analysis of the SAMP8 mouse brain through whole-genome transcriptomics not only deepens our understanding of age-related changes but also lays the groundwork for a predictive model to facilitate drug screening for cognitive aging.

Eligibility for Anti-Amyloid Treatment in a Population-Based Study of Cognitive Aging.

BACKGROUND AND OBJECTIVES: Treatment options for Alzheimer disease (AD) are limited and have focused mainly on symptomatic therapy and improving quality of life. Recently, lecanemab, an anti-ß-amyloid monoclonal antibody (mAb), received accelerated approval by the US Food and Drug Administration for treatment in the early stages of biomarker-confirmed symptomatic AD. An additional anti-ß-amyloid mAb, aducanumab, was approved in 2021, and more will potentially become available in the near future. Research on the applicability and generalizability of the anti-ß-amyloid mAb eligibility criteria on adults with biomarkers available in the general population has been lacking. The study's primary aim was to apply the clinical trial eligibility criteria for lecanemab treatment to participants with early AD of the population-based Mayo Clinic Study of Aging (MCSA) and assess the generalizability of anti-amyloid treatment. The secondary aim of this study was to apply the clinical trial eligibility criteria for aducanumab treatment in MCSA participants. METHODS: This cross-sectional study aimed to apply the clinical trial eligibility criteria for lecanemab and aducanumab treatment to participants with early AD of the population-based MCSA and assess the generalizability of anti-amyloid treatment. RESULTS: Two hundred thirty-seven MCSA participants (mean age [SD] 80.9 [6.3] years, 54.9% male, and 97.5% White) with mild cognitive impairment (MCI) or mild dementia and increased brain amyloid burden by PiB PET comprised the study sample. Lecanemab trial's inclusion criteria reduced the study sample to 112 (47.3% of 237) participants. The trial's exclusion criteria further narrowed the number of potentially eligible participants to 19 (overall 8% of 237). Modifying the eligibility criteria to include all participants with MCI (instead of applying additional cognitive criteria) resulted in 17.4% of participants with MCI being eligible for lecanemab treatment. One hundred four participants (43.9% of 237) fulfilled the aducanumab clinical trial's inclusion criteria. The aducanumab trial's exclusion criteria further reduced the number of available participants, narrowing those eligible to 12 (5.1% of 237). Common exclusions were related to other chronic conditions and neuroimaging findings. DISCUSSION: Findings estimate the limited eligibility in typical older adults with cognitive impairment for anti-ß-amyloid mAbs.

Characterizing Performance Gaps of a Code-Based Dementia Algorithm in a Population-Based Cohort of Cognitive Aging.

BACKGROUND: Multiple algorithms with variable performance have been developed to identify dementia using combinations of billing codes and medication data that are widely available from electronic health records (EHR). If the characteristics of misclassified patients are clearly identified, modifying existing algorithms to improve performance may be possible. OBJECTIVE: To examine the performance of a code-based algorithm to identify dementia cases in the population-based Mayo Clinic Study of Aging (MCSA) where dementia diagnosis (i.e., reference standard) is actively assessed through routine follow-up and describe the characteristics of persons incorrectly categorized. METHODS: There were 5,316 participants (age at baseline (mean (SD)): 73.3 (9.68) years; 50.7% male) without dementia at baseline and available EHR data. ICD-9/10 codes and prescription medications for dementia were extracted between baseline and one year after an MCSA dementia diagnosis or last follow-up. Fisher's exact or Kruskal-Wallis tests were used to compare characteristics between groups. RESULTS: Algorithm sensitivity and specificity were 0.70 (95% CI: 0.67, 0.74) and 0.95 (95% CI: 0.95, 0.96). False positives (i.e., participants falsely diagnosed with dementia by the algorithm) were older, with higher Charlson comorbidity index, more likely to have mild cognitive impairment (MCI), and longer follow-up (versus true negatives). False negatives (versus true positives) were older, more likely to have MCI, or have more functional limitations. CONCLUSIONS: We observed a moderate-high performance of the code-based diagnosis method against the population-based MCSA reference standard dementia diagnosis. Older participants and those with MCI at baseline were more likely to be misclassified.

Cognitive aging and experience of playing a musical instrument.

Musical instrument training has been found to be associated with higher cognitive performance in older age. However, it is not clear whether this association reflects a reduced rate of cognitive decline in older age (differential preservation), and/or the persistence of cognitive advantages associated with childhood musical training (preserved differentiation). It is also unclear whether this association is consistent across different cognitive domains. Our sample included 420 participants from the Lothian Birth Cohort 1936. Between ages 70 and 82, participants had completed the same 13 cognitive tests (every 3 years), measuring the cognitive domains of verbal ability, verbal memory, processing speed, and visuospatial ability. At age 82, participants reported their lifetime musical experiences; 40% had played a musical instrument, mostly in childhood and adolescence. In minimally adjusted models, participants with greater experience playing a musical instrument tended to perform better across each cognitive domain at age 70 and this association persisted at subsequent waves up to age 82. After controlling for additional covariates (childhood cognitive ability, years of education, socioeconomic status, and health variables), only associations with processing speed (ß = 0.131, p = .044) and visuospatial ability (ß = 0.154, p = .008) remained statistically significant. Participants with different amounts of experience playing a musical instrument showed similar rates of decline across each cognitive domain between ages 70 and 82. These results suggest a preserved differentiation effect: Cognitive advantages (in processing speed and visuospatial ability) associated with experience playing a musical instrument (mostly earlier in life) are preserved during older age. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Development and validation of educational multimedia to promote public health literacy about healthy cognitive aging.

OBJECTIVES: Health literacy (HL) about healthy cognitive aging is essential in preventing cognitive decline and promoting cognitive well-being. It is important that one such HL module should be scientifically designed, delivered in a technically sound manner to the audience, and specific to the context. The present study thus aimed at developing and validating educational multimedia about cognitive health. METHODS: The study followed a methodological framework and was carried out across three phases, that is, identification of themes, development and validation of educational script and design, and validation of educational multimedia. The module was scripted based on the Integrated HL framework and the recommendations made during the modified nominal group technique among the research team. Seven speech-language pathologists (SLPs), with expertise in the field of cognitive sciences, and 15 representatives of the general public validated the module using the Educational Content Validation Instrument in Health and the Patient Education Materials Assessment Tool for Audiovisual Materials questionnaire. RESULTS: The scientific content of the educational script received satisfactory agreements among the experts (content validity index [CVI]: 0.93) and representatives of the general public (CVI: 0.86). The technical aspects of the educational multimedia were rated to have high understandability (experts: 92.8%; representatives of general public: 98.8%) and actionability (experts and representatives of general public 100%). CONCLUSION: Overall, the developed educational multimedia scored optimally with respect to the objective, structure, relevance of the content, actionability and understandability of the multimedia. The developed module holds the potential to be used at community and national level health educational programs or awareness campaigns to enhance public knowledge and beliefs pertaining to cognitive health. PATIENT OR PUBLIC CONTRIBUTION: SLPs with expertise in the field of cognitive science and representatives from the general public were included to validate and obtain feedback on the developed educational multimedia.

Frailty and Processing Speed Performance at the Cusp of Midlife in CATSLife.

OBJECTIVES: Frailty is not an end state of aging, but rather represents physiological vulnerability across multiple systems that unfolds across adulthood. However, examinations of frailty at the midlife transition, and how frailty may impact other age-sensitive traits, such as processing speed (PS), remain scarce. Our research aims were to examine frailty and frailty-speed associations before midlife, a ripe developmental period for healthy aging interventions. METHODS: Using data from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (N = 1,215; Mage = 33.23 years; standard deviation = 4.98), we constructed 25-item (FI25) and 30-item (FI30) frailty indices. PS was measured using the Colorado Perceptual Speed task and WAIS-III Digit Symbol (DS) subtest. Multilevel models accounted for clustering among siblings and adjusted for sex, race, ethnicity, adoption status, educational attainment, and age. RESULTS: Reliability of FI measures was apparent from strong intraclass correlations (ICCs) among identical twin siblings, although ICC patterns across all siblings suggested that FI variability may include nonadditive genetic contributions. Higher FI was associated with poorer PS performance but was significant for DS only (BFI25 = -1.17, p = .001, d = -0.12; BFI30 = -1.21, p = .001, d = -0.12). Furthermore, the negative frailty-DS association was moderated by age (BFI25×age = -0.14, p = .042; BFI30×age=-0.19, p = .008) where increasingly worse performance with higher frailty emerged at older ages. DISCUSSION: Frailty is evident before midlife and associated with poorer PS, an association that magnifies with age. These findings help elucidate the interrelationship between indicators of frailty and cognitive performance for adults approaching midlife, an understudied period within life-span development.

The Overview of Cognitive Aging Models.

To understand the cause of the age-related decline in cognitive function and its underlying mechanism, the cognitive aging model can provide us with important insights. In this section, we will introduce behavioral and neural models about age-related cognitive changes. Among behavioral models, several aging theories were discussed from the perspectives of educational, biological, and sociological factors, which could explain parts of the aging process. With the development of imaging technology, many studies have discussed the neural mechanism of aging and successively proposed neural models to explain the aging phenomenon. Behavioral models and neural mechanism models supplement each other, gradually unveiling the mystery of cognitive aging.

Cognitive Aging: How the Brain Ages?

Cognitive aging refers to the cognitive changes or functional decline that comes with age. The relation between aging and functional declines involves various aspects of cognition, including memory, attention, processing speed, and executive function. In this chapter, we have introduced several dimensions about cognitive aging trajectories. Meanwhile, we have reviewed the history of the study of cognitive aging and expatiated two trends that are particularly noteworthy in the effort to elucidate the process of aging. One is that the differences between components of mental abilities have become gradually specified. The other one is a growing interest in the neural process, which relates changes in the brain structure to age-related changes in cognition. Lastly, as the basis of cognitive function, brain structures and functions change during aging, and these changes are reflected in a corresponding decline in cognitive function. We have discussed the patterns of reorganization of various structural and functional aging processes of the brain and their relationship with cognitive function.

Lifestyle Adjustment: Influential Risk Factors in Cognitive Aging.

Cognitive aging is inevitable. However, researchers have demonstrated that lifestyle adjustments can reduce the risk of cognitive impairment. A healthy diet style, the Mediterranean diet, has been proven to benefit the elderly. Oil, salt, sugar, and fat are, on the contrary, risk factors for cognitive dysfunction because of the resultant high caloric intake. Physical and mental exercises, especially cognitive training, are also beneficial for aging. At the same time, several risk factors need to be noted, such as smoking, alcohol consumption, insomnia, and excessive daytime sleeping, which are highly relative to cognitive impairment, cardiovascular diseases, and dementia.

Emotional and Affective Disorders in Cognitive Aging.

The increased aging population who have aging-related diseases poses a serious challenge to health services, including mental health services. Due to the changes of body, brain, living environment, and lifestyle, the elderly will have different psychological changes from other age stages, some of which would develop into mental disorders, and affect the cognition of the elderly in turn. This elderly mental health condition has drawn wide attention from scientists. This chapter introduces the two most common emotional and affective disorders, late-life depression and anxiety, and focuses on their epidemiology and impact on the elderly. Furthermore, this chapter also reviews the effects of these two disorders on cognitive function and cognitive impairment in the elderly, and tries to explain the underlying mechanism of this effect from the perspective of related disease, cerebral circuit, and molecular biology.

Neuropsychology of cognitive aging in rhesus monkeys.

Aged rhesus monkeys, like aged humans, show declines in cognitive function. We present cognitive test data from a large sample of male and female rhesus monkeys, 34 young (aged 3.5-13.6 years) and 71 aged (aged 19.9-32.5 years at the start of cognitive testing). Monkeys were tested on spatiotemporal working memory (delayed response), visual recognition memory (delayed nonmatching to sample), and stimulus-reward association learning (object discrimination), tasks with an extensive evidence base in nonhuman primate neuropsychology. On average, aged monkeys performed worse than young on all 3 tasks. Acquisition of delayed response and delayed nonmatching to sample was more variable in aged monkeys than in young. Performance scores on delayed nonmatching to sample and object discrimination were associated with each other, but neither was associated with performance on delayed response. Sex and chronological age were not reliable predictors of individual differences in cognitive outcome among the aged monkeys. These data establish population norms for multiple cognitive tests in young and aged rhesus monkeys in the largest sample reported to date. They also illustrate independence of cognitive aging in task domains dependent on the prefrontal cortex and medial temporal lobe.

Retirement and cognitive aging in a racially diverse sample of older Americans.

BACKGROUND: Retirement represents a crucial transitional period for many adults with possible consequences for cognitive aging. We examined trajectories of cognitive change before and after retirement in Black and White adults. METHODS: Longitudinal examination of up to 10 years (mean = 7.1 ± 2.2 years) using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study-a national, longitudinal study of Black and White adults ≥45 years of age. Data were from 2226 members of the REGARDS study who retired around the time when an occupational ancillary survey was administered. Cognitive function was an average of z-scores for tests of verbal fluency, memory, and global function. RESULTS: Cognitive functioning was stable before retirement (Estimate = 0.05, p = 0.322), followed by a significant decline after retirement (Estimate = -0.15, p < 0.001). The decline was particularly pronounced in White (Estimate = -0.19, p < 0.001) compared with Black (Estimate = -0.07, p = 0.077) participants, twice as large in men (Estimate = -0.20, p < 0.001) compared with women (Estimate = -0.11, p < 0.001), highest among White men (Estimate = -0.22, p < 0.001) and lowest in Black women (Estimate = -0.04, p = 0.457). Greater post-retirement cognitive decline was also observed among participants who attended college (Estimate = -0.14, p = 0.016). While greater work complexity (Estimate = 0.92, p < 0.05) and higher income (Estimate = 1.03, p < 0.05) were related to better cognitive function at retirement, neither was significantly related to cognitive change after retirement. CONCLUSION: Cognitive functioning may decline at an accelerated rate immediately post-retirement, more so in White adults and men than Black adults and women. Lifelong structural inequalities including occupational segregation and other social determinants of cognitive health may obscure the role of retirement in cognitive aging.