Impact of Mood Disorder History and Bone Health on Cognitive Function Among Men Without Dementia.

BACKGROUND: Poor cognitive function, a major disabling condition of older age, is often considered a prodromal feature of dementia. High mortality and the lack of a cure for dementia have necessitated a focus on the identification of potentially modifiable risk factors. Mental and physical health conditions such as mood disorders and bone loss have been previously linked with poor cognition individually although their combined effect remains largely unknown. OBJECTIVE: Considering the multifactorial nature of dementia pathology, we investigated whether mood disorders, bone health and their interaction are associated with cognitive function in a population-based sample of men. METHODS: Four hundred and forty-two male participants were drawn from the Geelong Osteoporosis Study. Cognitive function was assessed using the CogState Brief Battery, which measured cognitive performance across four domains and was used to compute overall cognitive function. Mood disorders and hip bone mineral density (BMD) were determined using a semi-structured clinical interview and dual-energy X-ray absorptiometry, respectively. RESULTS: Hip BMD (Bcoeff = 0.56, 95% CI: [0.07, 1.05], p = 0.025) but not mood disorder (Bcoeff = -0.50, 95% CI: [-0.20, 0.10], p = 0.529) was associated with overall cognitive function after accounting for potential confounders. Interaction effects were observed between the two exposures (Bcoeff = -1.37, 95% CI: [-2.49, -0.26], p = 0.016) suggesting that individuals without a mood disorder displayed better cognitive performance with increasing BMD, while those with a lifetime history of mood disorder displayed poorer cognitive function with increasing BMD. CONCLUSIONS: These findings highlight the importance of exploring interactions among potentially modifiable health conditions associated with cognitive function.

A plasma protein signature associated with cognitive function in men without severe cognitive impairment.

BACKGROUND: A minimally invasive blood-based assessment of cognitive function could be a promising screening strategy to identify high-risk groups for the incidence of Alzheimer's disease. METHODS: The study included 448 cognitively unimpaired men (mean age 64.1 years) drawn from the Geelong Osteoporosis Study. A targeted mass spectrometry-based proteomic assay was performed to measure the abundance levels of 269 plasma proteins followed by linear regression analyses adjusted for age and APOE ε4 carrier status to identify the biomarkers related to overall cognitive function. Furthermore, two-way interactions were conducted to see whether Alzheimer's disease-linked genetic variants or health conditions modify the association between biomarkers and cognitive function. RESULTS: Ten plasma proteins showed an association with overall cognitive function. This association was modified by allelic variants in genes ABCA7, CLU, BDNF and MS4A6A that have been previously linked to Alzheimer's disease. Modifiable health conditions such as mood disorders and poor bone health, which are postulated to be risk factors for Alzheimer's disease, also impacted the relationship observed between protein marker levels and cognition. In addition to the univariate analyses, an 11-feature multianalyte model was created using the least absolute shrinkage and selection operator regression that identified 10 protein features and age associated with cognitive function. CONCLUSIONS: Overall, the present study revealed plasma protein candidates that may contribute to the development of a blood-based screening test for identifying early cognitive changes. This study also highlights the importance of considering other risk factors in elucidating the relationship between biomarkers and cognition, an area that remains largely unexplored.

Genetic polymorphism in BIN1 rather than APOE is associated with poor recognition memory among men without dementia.

Although several genetic polymorphisms have been linked with the risk of Alzheimer's disease, less is known about their impact on cognitive performance among cognitively healthy individuals. Our aim was to investigate the association of the genetic variant, rs744373 in the bridging integrator 1 gene (BIN1), the strongest genetic risk factor for Alzheimer's disease after the APOE ε4 allele, with different cognitive domains among non-demented older men. Cognitive function was measured using the CogState Brief Battery, which assessed cognitive performance across four domains: psychomotor function, visual attention, recognition memory and working memory. Linear regression analysis revealed that individuals with the BIN1 risk allele performed poorly on the recognition memory task as compared to those without the risk allele. However, this was in contrast with the individuals who harboured the APOE ε4 risk allele as they displayed better performance on the recognition task in comparison to those without the ε4 risk allele. To the best of our knowledge, this is the first study that demonstrates genetic variation in BIN1 to be a better predictor of recognition memory than APOE, which remains the biggest genetic risk factor for Alzheimer's disease.

Depression and bone loss as risk factors for cognitive decline: A systematic review and meta-analysis.

BACKGROUND: Depression is linked to Alzheimer's disease (AD) but it is unclear whether depression is also associated with cognitive decline in the preclinical phase and mild cognitive impairment (MCI). Previous meta-analyses have only investigated AD as an outcome without accounting for individuals showing cognitive decline that does not meet the diagnostic criteria for AD. Other potentially modifiable risk factors such as bone loss have also been less explored and there remains uncertainty around their temporal relationship with cognitive decline. AIMS: To conduct a systematic review and meta-analysis investigating depression and bone loss as risk factors for subsequent cognitive decline. METHODS: A comprehensive search strategy was developed and applied using four databases; MEDLINE Complete, Embase, PsycINFO and CINAHL Complete. The pooled summary effects were estimated as odds ratios with 95% confidence intervals using a random-effects model. The study protocol was registered with PROSPERO (ID: CRD42020159369). RESULTS: A total of 75 longitudinal cohort studies were identified for meta-analysis, of which 70 examined the impact of depression on cognitive decline and five examined the impact of bone loss. Prior exposure to depression was found to be associated with cognitive score reduction (OR 1.33 95% CI 1.17, 1.51), MCI incidence (OR 1.52 95% CI 1.28, 1.79) and AD incidence (OR 1.79 95% CI 1.46, 2.2). Bone loss was also associated with the incidence of AD (OR=1.81 95% CI 1.28, 2.55). CONCLUSIONS: Overall, the results support the hypothesis that depression is associated with subsequent cognitive decline. Bone loss was also found to be associated with AD incidence; however, due to the small number of studies, the results should be viewed with caution.

Clinical utility of MRI and SPECT in the diagnosis of cognitive impairment referred to memory clinic.

ABSTRACTBackground:Despite of their limited availability and potential for significant variation between and within each modality, this is the first study to prospectively measure the clinical utility of MRI and/or SPECT brain scanning in addition to the routine diagnostic workup of patients presenting to memory clinic. METHODS: A single center study was conducted over a convenience of 12-month sampling period. For each patient referred for MRI and/or SPECT scanning, the primary geriatrician or psychogeriatrician was asked to assign an initial diagnosis. The initial diagnosis was then compared with the final consensus diagnosis after any scans or neuropsychology testing had been completed. RESULTS: During the 12-month study period, 66 patients (26%) were referred for scans out of a total of 253 patients included in the study. There were 16/44 (36%) positive MRI outcomes and 13/35 (37%) positive SPECT outcomes. The diagnosis changed consistent with the MRI scan findings in 11/44 (25%) and changed consistent with the SPECT scan findings in 9/35 (26%). Potentially reversible pathology was identified in a single patient, 1/50 (2%), via an MRI scan that suggested normal pressure hydrocephalus. The number needed to test for one positive outcome was 3.8 (95% CI 2.0-23.3), 6.0 (95% CI NA), and 1.7 (95% CI 1.3-2.5) for MRI only, SPECT only, and MRI and SPECT together, respectively. CONCLUSIONS: The clinical utility of MRI and/or SPECT scanning in this study may be broadly superior to the available international evidence, and further research is needed to identify predictors of positive scan outcomes.