Cognitive Decline In Older Men Research Articles

Differences in the association between midlife hypertension status and late‐life cognition and cognitive change: results from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study

AbstractBackgroundThis study evaluates the association of midlife hypertension status and domain‐specific late‐life cognitive change allowing for possible differences by sex.MethodThe Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort is a multi‐ethnic study of 1,712 Kaiser Permanente Northern California members age 65+ at enrollment in 2017. For 1,696 participants, we categorized the last examined clinical blood pressure measures from 1964‐1985 (mean age = 37.5) as hypotensive, normotensive, prehypertensive, or hypertensive. Verbal episodic memory and executive function were assessed using Spanish and English Neuropsychological Assessment Scales across three interview waves over 4 years and scores were z‐standardized to the baseline. Sex‐stratified linear mixed models with random intercepts estimated the associations of midlife hypertension status with domain‐specific baseline cognition and cognitive change using years since baseline as timescale. Models adjusted for age at blood pressure measurement, KHANDLE baseline age, race, ethnicity, education, practice effects, and interview mode (phone vs in‐person).ResultA greater proportion of men than women had midlife pre‐hypertension (44% vs 31%) or hypertension (21% vs 11%) (Table 1). Among men and women, midlife hypertension status was not associated with baseline executive function or verbal episodic memory (Table 2). Compared to men with normal midlife blood pressure, those with midlife hypotension (b = ‐0.10, 95% CI: ‐0.17, ‐0.04) or midlife hypertension experienced steeper declines in executive functioning (b = ‐0.05, 95% CI: ‐0.10, ‐0.004). Among women, only midlife hypertension was associated with decline in executive function (b = ‐0.04 95% CI: ‐0.09, 0.003), though not significantly different from normotensive women. Compared to normotensive men, those with midlife hypotension (b = ‐0.17, 95%CI: ‐0.27, ‐0.07) and those with pre‐hypertension (b = ‐0.06, 95% CI: ‐0.12, ‐0.004) experienced steeper decline in verbal episodic memory. Among women, only midlife hypertension was associated with steeper declines executive function (b = ‐0.04, 95% CI: ‐0.09, 0.003), though not significantly different from normotensive women. Though effect estimates of midlife hypertension status on cognitive outcomes differed by sex, these differences were not statistically significant.ConclusionBoth hypotension and hypertension 30‐50 years prior to cognitive assessments predicted accelerated cognitive decline in older men. Patterns were less consistent for women but not statistically distinguishable from associations among men.

Cardiovascular Disease Risk Scores and Incident Dementia and Cognitive Decline in Older Men and Women

Introduction: Risk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia risk in older adults who do not have a history of CVD, and potential gender differences in this association, remains unclear. The aim of this study was to determine whether CVD risk scores are prospectively associated with cognitive decline and dementia in initially healthy older men and women. Methods: A total of19,114 participants from a prospective cohort of individuals aged 65+ years without known CVD or dementia were recruited. The atherosclerotic cardiovascular disease risk score (ASCVDRS), Systematic Coronary Risk Evaluation 2-Older Persons (SCORE2-OP), and the Framingham risk score (FRS) were calculated at baseline. Risk of dementia (according to DSM-IV criteria) and cognitive decline (defined as a >1.5 standard deviation decline in global cognition, episodic memory, psychomotor speed, or verbal fluency from the previous year) were assessed using hazard ratio. Results: Over a median follow-up of 6.4 years, 850 individuals developed dementia and 4,352 cognitive decline. Men and women in the highest ASCVDRS tertile had a 41% (95% CI 1.08, 1.85) and 45% (1.11, 1.89) increased risk of dementia compared to the lowest tertile, respectively. Likewise, men and women in the highest SCORE2-OP tertile had a 64% (1.24, 2.16) and 60% (1.22, 2.11) increased risk of dementia compared to the lowest tertile, respectively. Findings were similar, but the risk was slightly lesser when examining risk of cognitive decline for both ASCVDRS and SCORE2-OP. However, FRS was only associated with the risk of cognitive decline among women (highest vs. lowest tertiles: 1.13 [1.01–1.26]). Conclusion: These findings suggest the utility of the ASCVDRS and SCORE2-OP in clinical practice, to not only assess future risk of CVD, but also as potential early indicators of cognitive impairment, even in relatively healthy older men and women.

Symbolic dynamics of sleep heart rate variability is associated with cognitive decline in older men.

We aimed to investigate the association between autonomic and cognitive functions in older men. We investigated heart rate variability (HRV) during sleep using time domain metrics and symbolic dynamics analysis of inter-beat intervals. These metrics were statistically analysed for associations with cognitive function which was elicited by administering the modified mini-mental state examination (3MS) and the Trail making test part-B in older men participating in the MrOS sleep study.Multivariable linear regression adjusted for age, body-mass-index (BMI), apnea-hypopnea index (AHI) and arousal index (A.I.) showed that symbolic dynamics of HRV especially the 0V% which is a measure of sympathetic outflow to the heart during rapid eye movement (REM) sleep is significantly associated with 3MS and Trail B scores. In conclusion, nonlinear HRV during sleep provides a unique window to probe the association between cognitive and autonomic function.Clinical Relevance- This study shows that cognitive decline is associated with altered cardiac autonomic function.

Age Acceleration is Associated with Reduced Cognitive Function in Older Men: Results from the Normative Aging Study

BACKGROUND AND AIM: DNA methylation (DNAm) has been used to quantify the biological effects of external factors on aging processes. This study examined the association between age acceleration and cognitive function in older men using DNAm-based clocks. METHODS: We evaluated the associations of age acceleration on cognitive function among participants in the Normative Aging Study (NAS). We tested GrimAgeAccel (a biomarker linked with mortality), PhenoAgeAccel (capturing risks for diverse outcomes), Intrinsic (IEAA), and Extrinsic (EEAA) Age Acceleration, and the DNAm-related mortality risk score (DNAmRS). DNAm was determined using Illumina 450K arrays. We modeled six cognitive tests (Mini-Mental State Examination [global function], Word List Memory Task [recent memory], Digit Span Backwards [executive function], Verbal Fluency Test [language], Sum of Drawings [visuospatial ability], and Pattern Comparison Task [visuospatial function]) in linear mixed models adjusted for chronological age, alcohol, smoking status, fish consumption, physical activity, hypertension, diabetes mellitus, English as the first language, computer experience, education, body mass index, and methylation technical covariates. RESULTS: We evaluated 549 men (mean age: 74.3 years, standard deviation: 6.5 years), mostly white (91.23%). GrimAgeAccel showed significant negative associations with global cognition (β = -0.029, 95% Confidence Interval [95%CI] -0.043, -0.015, p-value < 0.001) and visospatial ability (β = -0.018, 95% CI -0.033, -0.003, p-value = 0.019). PhenoAgeAccel was negatively associated with executive function (β = -0.009, 95% CI -0.017, -0.001, p-value = 0.041) and visuospatial ability (β = -0.019, 95% CI -0.029, -0.008, p-value < 0.001). DNAmRS was negatively associated with recent memory and executive function. IEAA and EEAA did not show consistent results. CONCLUSIONS: Selected age acceleration biomarkers were associated with accelerated cognitive decline in older men. DNAm-based biological clocks may help identify individuals at higher risk for age-related cognitive decline. KEYWORDS: Aging, age acceleration, cognitive function, age-related, DNA methylation.

Functional Fitness and Cognition in Older Adults: A Mediation Model

Purpose Investigate the mediating effects of functional fitness on age-related cognitive decline in older adults. Design Cross-sectional study. Methods A sample of 427 community-dwelling older adults reported their medical history and sociodemographic characteristics. Functional fitness was assessed based on the sit-and-reach, grip strength, sit to stand, agility, single-leg stance time and the 6-minute walk tests. Cognitive performance was assessed using the Mini-Mental State Examination. Multilevel mediation models were applied to assess the relationship between age and cognitive status. Results In women, the relationship between age and cognitive decline (β = −0.08; P < 0.05) was attenuated by agility (β = −0.05; P < 0.05) and balance (β = −0.4; P < 0.05). However, none of the functional fitness tests affected the relationship between age and cognitive decline in older men. Conclusion Agility and balance attenuated the relationship between age and cognitive decline among older women by 50% and 40%, respectively.

Androgen receptor CAG repeat length as a moderator of the relationship between free testosterone levels and cognition

Age-related decrease in testosterone levels is a potential risk factor for cognitive decline in older men. However, observational studies and clinical trials have reported inconsistent results on the effects of testosterone on individual cognitive domains. Null findings may be attributed to factors that studies have yet to consider. In particular, individual variations in polyglutamine (CAG) length in the androgen receptor (AR) gene could alter androgenic activity in brain regions associated with cognitive processes including memory and executive functions. However, the role of AR CAG repeat length as a moderator of the relationship between testosterone levels and cognition has not been investigated. Therefore, we aimed to examine the relationship between baseline calculated free testosterone (cFT) levels, change in cFT levels over 18 months and CAG repeat length on cognitive performance in memory, executive function, language, attention and processing speed domains. These relationships were examined in 304 cognitively normal older male participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. In the attention and processing speed domain, a short CAG repeat length appears to exacerbate the effects of low baseline cFT levels that are also lower than expected at follow-up. These results highlight that individual variations in AR CAG repeat length should be considered in future studies and clinical trials that examine the complex relationship between testosterone and cognition.

Diabetic Retinopathy and Cognitive Decline in Older People with Type 2 Diabetes

Objective: Cerebral microvascular disease associated with type 2 diabetes (T2D) may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations. An hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with T2D. Research design and methods: In our study 54 men and women aged 60-75 years with T2D underwent standard standard retinal examination and a battery of cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using Diabetic Retinopathy Scale. Results: A significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, cardiovascular risk factors, and macrovascular disease. Conclusions: DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation.

APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Association of Androgens and Gonadotropins with Amnestic Mild Cognitive Impairment and Probable Alzheimer's Disease in Chinese Elderly Men.

Age-related hormone changes play important roles in cognitive decline in older men, and apolipoprotein E ɛ4 (APOEɛ4) is a risk factor for Alzheimer's disease (AD). This study aimed to investigate the interactive role of androgen decline and APOEɛ4 genotype in the pathogenesis of amnestic mild cognitive impairment (aMCI) and AD. In total, 576 elderly men over 65 years old from communities in Shijiazhuang were enrolled in this study, including 243 with normal cognition (NC), 271 with aMCI, and 62 with probable AD. Cognitive function was evaluated with a battery of neuropsychological tests. The serum levels of androgen and gonadotropin were detected by ELISA and chemiluminescence immunoassay. The levels of free testosterone (FT) and dihydrotestosterone (DHT) were lower in the aMCI group (p < 0.05), and even lower in the AD group (p < 0.001), but the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH)were higher in AD group (p < 0.01), comparing with that in NC or aMCI group. The interaction of lower FT or DHT levels with APOEɛ4 had a risk role in global cognitive impairment (p < 0.05). The area under the curve (AUC) of the ROC curve for predicting aMCI by serum FT levels was 0.745. These results indicated that the interaction of androgen decline and APOEɛ4 genotype play a role in aMCI and AD. Serum FT levels have a predictive value for aMCI and might be a potential biomarker for prodromal AD.

Gender-stratified analyses reveal longitudinal associations between social support and cognitive decline in older men

Objectives: Research has extensively examined the relationship between social support and health outcomes in older adults. Little is known, however, about the longitudinal associations between distinct dimensions of perceived social support and incident cognitive decline. The current longitudinal study examined whether dimensions of perceived social support were associated with increased risk of cognitive decline, and if the relationship differed by gender.Methods: 493 community-residing non-demented older adults were assessed for baseline social support via the Medical Outcomes Study-Social Support Survey (MOS-SSS). Incident cognitive impairment was determined using a 1 standard deviation below age and education adjusted total score on the Repeatable Battery for the Assessment of Neuropsychological Status Cox proportional-hazard models were used to analyze incident risk of cognitive impairment.Results: Higher perceived support, overall and in specific domains, at baseline was associated with increased risk of incident cognitive impairment. Further gender-stratified analyses revealed that higher perceived support at baseline was associated with increased risk of incident cognitive impairment only among males.Conclusion: Contrary to previous research, results from this longitudinal study suggest that perceived support might be an important risk factor for cognitive decline, notably in males, and should be integrated into multifactorial risk assessment and intervention procedures.

Periodic Limb Movements in Sleep are Associated with Greater Cognitive Decline in Older Men without Dementia.

To examine the association between periodic limb movements in sleep (PLMS) and change in selected aspects of cognition in community-dwelling older men. We studied 2,636 older men without dementia who underwent in-home polysomnography with measurement of the periodic limb movement index (PLMI) and periodic limb movement arousal index (PLMAI) using piezoelectric sensors. Random-effects models and logistic regression were used to examine the association between PLMI, PLMAI, and 3- to 4-y change in cognition. After multivariable adjustment, men with a high PLMI had greater decline on the Trail Making Test - Part B (P trend = 0.02); those with a PLMI ≥ 30 were 48% more likely (odds ratio = 1.48, 95% confidence interval = 1.05-2.07) to experience the development of significant cognitive impairment (≥ 1 SD above mean change). Further adjustment for sleep efficiency, nocturnal hypoxemia, or dopaminergic medication use and analysis among men without Parkinson disease (n = 2,607) showed similar findings. No significant association was found for PLMAI or for Modified Mini-Mental State Examination scores. Among older men without dementia, higher PLMS frequency was associated with greater decline in cognition, particularly in executive function.

PHYSICAL ACTIVITY ACROSS ADULTHOOD AND SUBJECTIVE COGNITIVE DECLINE IN OLDER MEN

PHYSICAL ACTIVITY ACROSS ADULTHOOD AND SUBJECTIVE COGNITIVE DECLINE IN OLDER MEN

Longitudinal Relationships between Reproductive Hormones and Cognitive Decline in Older Men: The Concord Health and Ageing in Men Project.

The longitudinal relationship between declining levels of reproductive hormones and cognitive function remains unclear in older men. The objective of this study was to examine the temporal relationship between changes in major reproductive hormone levels and cognitive decline over time. Men age 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) were assessed at baseline (2005-2007; n = 1705), 2-year followup (2007-2009; n = 1367), and 5-year followup (2010-2013; n = 958). At all assessments, T, dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, and SHBG, LH, and FSH by immunoassay. Dementia was diagnosed at baseline by clinical assessment and review by a specialist panel. Cognitive function was measured at all three assessments by the Mini Mental State Examination. None of the baseline reproductive hormones predicted cognitive decline in men without dementia over 5 years. However, the change in serum hormones over time was associated with cognitive decline. In univariate analysis, change in all the studied hormones, except for E2, was significantly associated with cognitive decline. However, in multivariate-adjusted models accounting for potential confounders, only change in serum T (β = 0.067), DHT (β = 0.394), calculated free T (β = 0.005), and E1 (β = 0.009) remained significantly associated (P < .05) with cognitive decline. Men who had dementia at baseline had significantly greater decline in serum T levels, but not in other studied hormones, over the 5 years. Our findings show that decline in androgen status is associated with cognitive decline in older men, but the causality of this association requires further elucidation.

Vitamin D deficiency predicts cognitive decline in older men and women: The Pro.V.A. Study.

To test the hypothesis that hypovitaminosis D is associated with a higher risk of cognitive decline over a 4.4-year follow-up in a large sample of older adults. This research was part of the Progetto Veneto Anziani (Pro.V.A.), an Italian population-based cohort study of 1,927 elderly subjects. Serum 25-hydroxyvitamin D (25OHD) levels were measured at the baseline. Global cognitive function was measured with the Mini-Mental State Examination (MMSE); scores lower than 24 were indicative of cognitive dysfunction, and a decline of 3 or more points on the MMSE over the follow-up was considered as clinically significant. Analyses were adjusted for relevant confounders, including health and performance status. Participants with 25OHD deficiency (<50 nmol/L) or insufficiency (50-75 nmol/L) were more likely to have declining MMSE scores during the follow-up than those who were 25OHD sufficient (≥75 nmol/L). Among participants cognitively intact (baseline MMSE scores ≥24 and without diagnosis of dementia), the multivariate adjusted relative risk (95% confidence interval [CI]) of the onset of cognitive dysfunction was 1.36 (95% CI: 1.04-1.80; p = 0.02) for those with vitamin D deficiency and 1.29 (95% CI: 1.00-1.76; p = 0.05) for those with vitamin D insufficiency by comparison with individuals with normal 25OHD levels. The results of our study support an independent association between low 25OHD levels and cognitive decline in elderly individuals. In cognitively intact elderly subjects, 25OHD levels below 75 nmol/L are already predictive of global cognitive dysfunction at 4.4 years.

Lead exposure and rate of change in cognitive function in older women

BackgroundHigher long-term cumulative lead exposure predicts faster cognitive decline in older men, but evidence of an association in women is lacking. ObjectiveTo determine if there is an association between lead exposure and cognitive decline in women. MethodsThis study considers a sample of 584 women from the Nurses' Health Study who live in or near Boston, Massachusetts. We quantified lead exposure using biomarkers of lead exposure assessed in 1993–2004 and evaluated cognitive decline by repeated performance on a telephone battery of cognitive tests primarily assessing learning, memory, executive function, and attention completed in 1995–2008. All cognitive test scores were z-transformed for use in analyses. We used linear mixed models with random effects to quantify the association between each lead biomarker and change in cognition overall and on each individual test. ResultsConsideration of individual tests showed greater cognitive decline with increased tibia lead concentrations, a measure of long-term cumulative exposure, for story memory and category fluency. The estimated excess annual decline in overall cognitive test z-score per SD increase in tibia bone lead concentration was suggestive, although the confidence intervals included the null (0.024 standard units, 95% confidence interval: −0.053, 0.004 – an additional decline in function equivalent to being 0.33 years older). We found little support for associations between cognitive decline and patella or blood lead, which provide integrated measures of exposure over shorter timeframes. ConclusionsLong-term cumulative lead exposure may be weakly associated with faster cognitive decline in community-dwelling women, at least in some cognitive domains.

The hormonal pathway to cognitive impairment in older men.

In older men there is a multiple hormonal dysregulation with a relative prevalence of catabolic hormones such as thyroid hormones and cortisol and a decline in anabolic hormones such as dehydroepiandrosterone sulphate, testosterone and insulin like growth factor 1 levels. Many studies suggest that this catabolic milieu is an important predictor of frailty and mortality in older persons. There is a close relationship between frailty and cognitive impairment with studies suggesting that development of frailty is consequence of cognitive impairment and others pointing out that physical frailty is a determinant of cognitive decline. Decline in cognitive function, typically memory, is a major symptom of dementia. The "preclinical phase" of cognitive impairment occurs many years before the onset of dementia. The identification of relevant modifiable factors, including the hormonal dysregulation, may lead to therapeutic strategies for preventing the cognitive dysfunction. There are several mechanisms by which anabolic hormones play a role in neuroprotection and neuromodulation. These hormones facilitate recovery after brain injury and attenuate the neuronal loss. In contrast, elevated thyroid hormones may increase oxidative stress and apoptosis, leading to neuronal damage or death. In this mini review we will address the relationship between low levels of anabolic hormones, changes in thyroid hormones and cognitive function in older men. Then, giving the contradictory data of the literature and the multi-factorial origin of dementia, we will introduce the hypothesis of multiple hormonal derangement as a better determinant of cognitive decline in older men.

Forced Expiratory Volume in 1 Second and Cognitive Aging in Men

To evaluate forced expiratory volume in 1 second (FEV(1) , a measure of overall lung function), long-term average FEV(1) , and rate of decline in FEV(1) in relation to cognition and cognitive decline in older men. Prospective observational study. Community-based population. Eight hundred sixty-four older men from the Normative Aging Study. Starting in 1984, participants underwent triennial clinical evaluations. Lung function assessments provided estimates of FEV(1) . Cognitive assessments entailing tests of several cognitive abilities began in 1993. FEV(1) measured approximately 12 years before baseline cognitive testing, average FEV(1) over the 12-year period, and rate of change in FEV(1) were all evaluated in relation to baseline and change in performance on the cognitive tests. In multivariable-adjusted analyses, associations between FEV(1) and baseline cognitive scores were mixed, although average FEV(1) predicted significantly better performance on tests of visuospatial ability (P=.04) and general cognition (P=.03). Higher FEV(1) was more consistently associated with slower cognitive decline, but only the association between historical FEV(1) and attention was significant (difference per standard deviation in FEV(1) =0.056, P=.05). Rate of FEV(1) decline was not consistently associated with cognitive function or decline. Findings were generally similar or stronger in men who had never smoked. To account for potential bias due to selective attrition, inverse probability of censoring weights were applied to the cognitive decline analyses, yielding slightly larger estimates; the inadequate prognostic power of the censoring models limited this approach. Overall, the data provide limited evidence of an inverse association between FEV(1) and cognitive aging.

11β-hydroxysteroid dehydrogenase type 1, brain atrophy and cognitive decline

Excess cortisol levels are linked with brain atrophy and cognitive decline in older people. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) potently amplifies intracellular glucocorticoid action by converting inert cortisone to active cortisol, but any causal importance in brain aging is unexplored. We tested the hypotheses that higher systemic 11β-HSD1 activity predicts brain atrophy and cognitive decline in older men. In a longitudinal study of 41 men (65-70 years old at baseline) we measured baseline systemic 11β-HSD1 activity, the urinary 5alpha- and 5beta-tetrahydrocortisol to tetrahydrocortisone ratio (ratio of tetrahydrometabolites of cortisol (THFs)/ratio of tetrahydrometabolites of cortisol (THE)), and assessed change in brain atrophy, white matter lesions and cognitive function over 6 years. Baseline THFs/THE correlated negatively with baseline hippocampal volumes (left: r = -0.37; right: r = -0.34; p < 0.05) and positively with ventricular volumes (r = 0.43, p = 0.006) and periventricular white matter lesions (rho = 0.31, p = 0.047). Importantly, baseline THFs/THE but not cortisol predicted increase in ventricular volumes (r = 0.33, p = 0.037) and decline in processing speed (r = -0.55, p = 0.0002) over 6 years. The predictive link between systemic 11β-HSD1 activity and progressive brain atrophy and cognitive decline suggests 11β-HSD1 inhibition as a plausible therapy for brain aging.

Diabetic Retinopathy and Cognitive Decline in Older People With Type 2 Diabetes

OBJECTIVECerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.RESEARCH DESIGN AND METHODSIn the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60–75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.RESULTSAfter age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.CONCLUSIONSDR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation.

Tooth Loss and Periodontal Disease Predict Poor Cognitive Function in Older Men

To determine whether rates of tooth loss, periodontal disease progression, and caries incidence predict cognitive decline in men. Prospective study. Community-dwelling men enrolled in the Veterans Affairs Dental Longitudinal Study. Five hundred ninety-seven dentate men aged 28 to 70 at study baseline who have been followed up to 32 years. Oral examinations were conducted approximately every 3 years. Periodontal disease measures included probing pocket depth and radiographic alveolar bone height. Participants underwent cognitive testing beginning in 1993. Low cognitive status was defined as less than 25 points or less than 90% of the age- and education-specific median on the Mini-Mental State Examination (MMSE) and less than 10 points on a spatial copying task. Each tooth lost per decade since the baseline dental examination increased the risks of low MMSE score (hazard ratio (HR)=1.09, 95% confidence interval (CI)=1.01-1.18) and low spatial copying score (HR=1.12, CI=1.05-1.18). Risks were greater per additional tooth with progression of alveolar bone loss (spatial copying: HR=1.03, CI=1.01-1.06), probing pocket depth (MMSE: HR=1.04, CI=1.01-1.09; spatial copying: HR=1.04, CI=1.01-1.06), and caries (spatial copying: HR=1.05, CI=1.01-1.08). Risks were consistently higher in men who were older than 45.5 at baseline than in younger men. Risk of cognitive decline in older men increases as more teeth are lost. Periodontal disease and caries, major reasons for tooth loss, are also related to cognitive decline.