It remains uncertain whether long-term use of benzodiazepines is associated with age-related cognitive decline, and if cognitive ability in early life is the driver of any association. This study examines the association of cognitive ability in young adulthood with later use of benzodiazepines and explores whether the use of benzodiazepines during adult life is associated with cognitive decline in late midlife.

The study samples include cognitive tests on the Børge Priens Prøve (BPP) from the conscription board examination (age 19 years) from 335 513 men born 1949–1961 and data from re-examinations of 5183 men 44 years later. Cognitive decline was defined as the difference between scores at the conscription board and the re-examination. Information on purchases of benzodiazepines was obtained from the Danish National Prescription Registry, 1995–2022. Associations were analysed using Cox proportional hazards and linear regression.

In total, 120 911 (36%) men purchased benzodiazepines during a follow-up of 20 years. Lower cognitive scores in young adulthood were associated with a higher risk of initiating benzodiazepines (hazard ratio [95% CI] = 0.71[0.68–0.75]). Men with the highest cumulative use of benzodiazepines had larger cognitive decline (β-coefficient [95% CI] = −1.66 [−2.09 to −1.23] BPP scores) compared with never users. Current benzodiazepine users showed a larger cognitive decline than never users (β-coefficient [95% CI] = −2.42[−3.18 to −1.66] BPP scores) and this partially explained the above association. These estimates for cognitive decline were relatively small and may lack clinical relevance.

Low cognitive ability increases the risk of benzodiazepine use in adulthood and cognitive decline is more pronounced in those with the highest benzodiazepine use compared with never-use, but the difference lacks clinical significance.

To determine whether poorer performance on the Boston Naming Test (BNT) in individuals with transactive response DNA-binding protein 43 pathology (TDP-43+) is due to greater loss of word knowledge compared to retrieval-based deficits.

Retrospective clinical-pathologic study of 282 participants with Alzheimer’s disease neuropathologic changes (ADNC) and known TDP-43 status. We evaluated item-level performance on the 60-item BNT for first and last available assessment. We fit cross-sectional negative binomial count models that assessed total number of incorrect items, number correct of responses with phonemic cue (reflecting retrieval difficulties), and number of “I don’t know” (IDK) responses (suggestive of loss of word knowledge) at both assessments. Models included TDP-43 status and adjusted for sex, age, education, years from test to death, and ADNC severity. Models that evaluated the last assessment adjusted for number of prior BNT exposures.

43% were TDP-43+. The TDP-43+ group had worse performance on BNT total score at first (p = .01) and last assessments (p = .01). At first assessment, TDP-43+ individuals had an estimated 29% (CI: 7%–56%) higher mean number of incorrect items after adjusting for covariates, and a 51% (CI: 15%–98%) higher number of IDK responses compared to TDP-43−. At last assessment, compared to TDP-43−, the TDP-43+ group on average missed 31% (CI: 6%–62%; p = .01) more items and had 33% more IDK responses (CI: 1% fewer to 78% more; p = .06).

An important component of poorer performance on the BNT in participants who are TDP-43+ is having loss of word knowledge versus retrieval difficulties.

Post-traumatic stress disorder (PTSD) is associated with cognitive impairments. It is unclear whether problems persist after PTSD symptoms remit.

Data came from 12 270 trauma-exposed women in the Nurses' Health Study II. Trauma and PTSD symptoms were assessed using validated scales to determine PTSD status as of 2008 (trauma/no PTSD, remitted PTSD, unresolved PTSD) and symptom severity (lifetime and past-month). Starting in 2014, cognitive function was assessed using the Cogstate Brief Battery every 6 or 12 months for up to 24 months. PTSD associations with baseline cognition and longitudinal cognitive changes were estimated by covariate-adjusted linear regression and linear mixed-effects models, respectively.

Compared to women with trauma/no PTSD, women with remitted PTSD symptoms had a similar cognitive function at baseline, while women with unresolved PTSD symptoms had worse psychomotor speed/attention and learning/working memory. In women with unresolved PTSD symptoms, past-month PTSD symptom severity was inversely associated with baseline cognition. Over follow-up, both women with remitted and unresolved PTSD symptoms in 2008, especially those with high levels of symptoms, had a faster decline in learning/working memory than women with trauma/no PTSD. In women with remitted PTSD symptoms, higher lifetime PTSD symptom severity was associated with a faster decline in learning/working memory. Results were robust to the adjustment for sociodemographic, biobehavioral, and health factors and were partially attenuated when adjusted for depression.

Unresolved but not remitted PTSD was associated with worse cognitive function assessed six years later. Accelerated cognitive decline was observed among women with either unresolved or remitted PTSD symptoms.

Older brain age – as estimated from structural MRI data – is known to be associated with detrimental mental and physical health outcomes in older adults. Social isolation, which has similar detrimental effects on health, may be associated with accelerated brain aging though little is known about how different trajectories of social isolation across the life course moderate this association. We examined the associations between social isolation trajectories from age 5 to age 38 and brain age assessed at age 45.

We previously created a typology of social isolation based on onset during the life course and persistence into adulthood, using group-based trajectory analysis of longitudinal data from a New Zealand birth cohort. The typology comprises four groups: ‘never-isolated’, ‘adult-only’, ‘child-only’, and persistent ‘child-adult’ isolation. A brain age gap estimate (brainAGE) – the difference between predicted age from structural MRI date and chronological age – was derived at age 45. We undertook analyses of brainAGE with trajectory group as the predictor, adjusting for sex, family socio-economic status, and a range of familial and child-behavioral factors.

Older brain age in mid-adulthood was associated with trajectories of social isolation after adjustment for family and child confounders, particularly for the ‘adult-only’ group compared to the ‘never-isolated’ group.

Although our findings are associational, they indicate that preventing social isolation, particularly in mid-adulthood, may help to avert accelerated brain aging associated with negative health outcomes later in life.

1. (1) Recently, studies have shown that CBT for older people living with dementia has been effective in treating their depression and anxiety. However, evidence for the efficacy of CBT and other curative or care options for people living with dementia is limited in Japan.

2. (2) We studied a short-period CBT program and found that it was likely to be feasible and acceptable for use among older Japanese people with mild cognitive impairment, that it may improve negative mood among this group, and that it may lessen the care burden for caregivers.

3. (3) Furthermore, we found that caregiver involvement in the implementation of CBT for older people may be effective in improving the mood of family members.

Serial position scores on verbal memory tests are sensitive to early Alzheimer’s disease (AD)-related neuropathological changes that occur in the entorhinal cortex and hippocampus. The current study examines longitudinal change in serial position scores as markers of subtle cognitive decline in older adults who may be in preclinical or at-risk states for AD.

This study uses longitudinal data from the Religious Orders Study and the Rush Memory and Aging Project. Participants (n = 141) were included if they did not have dementia at enrollment, completed follow-up assessments, and died and were classified as Braak stage I or II. Memory tests were used to calculate serial position (primacy, recency), total recall, and episodic memory composite scores. A neuropathological evaluation quantified AD, vascular, and Lewy body pathologies. Mixed effects models were used to examine change in memory scores. Neuropathologies and covariates (age, sex, education, APOE e4) were examined as moderators.

Primacy scores declined (β = −.032, p < .001), whereas recency scores increased (β = .021, p = .012). No change was observed in standard memory measures. Greater neurofibrillary tangle density and atherosclerosis explained 10.4% of the variance in primacy decline. Neuropathologies were not associated with recency change.

In older adults with hippocampal neuropathologies, primacy score decline may be a sensitive marker of early AD-related changes. Tangle density and atherosclerosis had additive effects on decline. Recency improvement may reflect a compensatory mechanism. Monitoring for changes in serial position scores may be a useful in vivo method of tracking incipient AD.

Adverse childhood experiences (ACEs) have been associated with numerous health consequences in adulthood including cognitive decline. However, the underlying mechanisms implicated remain unclear.

In this study, depressive symptoms and systemic inflammation were investigated as potential independent mediators of the association between ACEs and cognitive decline.

Participants were adults aged 50+ from the English Longitudinal Study of Ageing (N = 3,029; 54.8% female). Measures included self-reported ACEs at wave 3 (2006-2007), C-reactive protein (CRP) and depressive symptoms at wave 4 (2008-2009), and cognitive function at waves 3 and 7 (2014-2015). Mediation analyses examined the direct associations between ACEs and cognitive function at wave 7 and the indirect associations via depressive symptoms and CRP at wave 4 and were conducted using ordinary least squares regression models with the SPSS PROCESS macro. In Step 1, models were adjusted for sociodemographic factors and baseline cognitive function. Models in Step 2 were additionally adjusted for obesity and health behaviours (n = 1,874).

Cumulative ACEs exposure was shown to positively predict later-life depressive symptoms, which in turn predicted cognitive decline. ACEs were also shown to positively predict systemic inflammation as measured by CRP. However, CRP did not mediate the association between ACEs and cognitive decline.

These findings suggest that ACEs are related to cognitive decline partly via depressive symptoms and corroborate prior research linking ACEs with adult systemic inflammation. Efforts towards screening for, preventing, and mitigating the effects of ACEs may therefore represent an important avenue for improving health outcomes in later life.

No significant relationships.

To evaluate whether cerebrospinal fluid biomarkers, apolipoprotein e4, neuroimaging abnormalities, and neuropsychological data differentially predict progression from mild cognitive impairment (MCI) to dementia for men and women.

Participants who were diagnosed with MCI at baseline (n = 449) were classified as either progressing to Alzheimer’s dementia at follow-up or as not progressing. Men and women were first compared using bivariate analyses. Sex-stratified Cox proportional hazard regressions were performed examining the relationship between baseline data and the likelihood of progressing to dementia. Sex interactions were subsequently examined.

Cox proportional hazard regression controlling for age and education indicated that all variables significantly predicted subsequent progression to dementia for men and women. Sex interactions indicated that only Rey Auditory Verbal Learning Test (RAVLT) delayed recall and Functional Activities Questionnaire (FAQ) were significantly stronger risk factors for women. When all variables were entered into a fully adjusted model, significant risk factors for women were Aβ42, hippocampal volume, RAVLT delayed recall, Boston Naming Test, and FAQ. In contrast, for men, Aβ42, p-tau181, p-tau181/Aβ42, hippocampal volume, category fluency and FAQ were significant risk factors. Interactions with sex were only significant for p-tau181/Aβ42 and RAVLT delayed recall for the fully adjusted model.

Men and women with MCI may to differ for which factors predict subsequent dementia although future analyses with greater power are needed to evaluate sex differences. We hypothesize that brain and cognitive reserve theories may partially explain these findings.

To determine associations of alcohol use with cognitive aging among middle-aged men.

1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003–2007 to 2016–2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1–4 drinks in past 14 days), light (5–14 drinks), moderate (15–28 drinks), and at-risk drinkers (>28 drinks in past 14 days). Linear mixed-effects regressions modeled cognitive trajectories by alcohol group, with time-based models evaluating rate of decline as a function of baseline alcohol use, and age-based models evaluating age-related differences in performance by current alcohol use. Analyses used standardized cognitive domain factor scores and adjusted for sociodemographic and health-related factors.

Performance decreased over time in all domains. Relative to very light drinkers, former drinkers showed worse verbal fluency performance, by –0.21 SD (95% CI –0.35, –0.07), and at-risk drinkers showed faster working memory decline, by 0.14 SD (95% CI 0.02, –0.20) per decade. There was no evidence of protective associations of light/moderate drinking on rate of decline. In age-based models, light drinkers displayed better memory performance at advanced ages than very light drinkers (+0.14 SD; 95% CI 0.02, 0.20 per 10-years older age); likely attributable to residual confounding or reverse association.

Alcohol consumption showed minimal associations with cognitive aging among middle-aged men. Stronger associations of alcohol with cognitive aging may become apparent at older ages, when cognitive abilities decline more rapidly.

Alzheimer’s disease (AD) is highly heritable, and AD polygenic risk scores (AD-PRSs) have been derived from genome-wide association studies. However, the nature of genetic influences very early in the disease process is still not well known. Here we tested the hypothesis that an AD-PRSs would be associated with changes in episodic memory and executive function across late midlife in men who were cognitively unimpaired at their baseline midlife assessment..

We examined 1168 men in the Vietnam Era Twin Study of Aging (VETSA) who were cognitively normal (CN) at their first of up to three assessments across 12 years (mean ages 56, 62, and 68). Latent growth models of episodic memory and executive function were based on 6–7 tests/subtests. AD-PRSs were based on Kunkle et al. (Nature Genetics, 51, 414–430, 2019), p < 5×10−8 threshold.

AD-PRSs were correlated with linear slopes of change for both cognitive abilities. Men with higher AD-PRSs had steeper declines in both memory (r = −.19, 95% CI [−.35, −.03]) and executive functioning (r = −.27, 95% CI [−.49, −.05]). Associations appeared driven by a combination of APOE and non-APOE genetic influences.

Memory is most characteristically impaired in AD, but executive functions are one of the first cognitive abilities to decline in midlife in normal aging. This study is among the first to demonstrate that this early decline also relates to AD genetic influences, even in men CN at baseline.

Dementia is a major cause of disability worldwide. About 25%-40% of patients with mild to moderate dementia are affected by sleep-awake cycle disturbances, including increased daytime sleepiness and insomnia. However, little is known about the specific impact of excessive daytime sleepiness on the cognitive decline of dementia patients.

To evaluate the impact of daytime sleepiness on the cognitive decline of dementia patients. Additionally, longitudinal associations with functional impairment and neuropsychiatric symptoms will be explored.

A longitudinal study will be conducted in a psychogeriatric consultation. Patients will be consecutively invited according to predefined eligibility criteria. Those aged ≥65 years, with dementia diagnosis or Mini-Mental State Examination (MMSE) <24, and with a knowledgeable caregiver, will be included. The exclusion criteria are: a caregiver <18 years, terminally ill, incapable to communicate or with a known diagnosis of insomnia, sleep related respiratory disorders, central hyperinsomnia, restless legs syndrome or sleep paralysis. Participants will undergo an assessment with a comprehensive protocol including: Montreal Cognitive Assessment (MoCA), Barthel and Lawton Index, Epworth Sleepiness Scale (ESS), Neuropsychiatric Inventory (NPI) and Global Deterioration Scale (GDS). Participants will be re-assessed 6 months after the initial evaluation. The Health Ethics Committee of Hospital Universitário de São João granted the study authorization (nº 260/2020).

Findings will be disseminated via publication in peer-reviewed journals and presentations at national and international scientific conferences.

This study will address key questions on the relation of daytime sleepiness and dementia outcomes, in order to undertake corrective and preventive non-pharmacological and pharmacological approaches.