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Objective: To determine if there is a synergistic effect between clinically relevant depressive symptoms and cardiovascular risk factors that disproportionately increases the risk of cardiovascular disease (CVD) among older adults with depressive symptoms.Methods: Data were obtained from the Longitudinal Aging Study Amsterdam, a longitudinal cohort study. N = 3091 respondents with up to seven years of follow-up were included. Incident CVD was based on self-report, medication use, general practitioners' diagnoses and causes of death. A score of ≥16 points on the Center for Epidemiological Studies Depression Scale indicated clinically relevant depressive symptoms. Risk factors included were sex, education, obesity, smoking, alcohol use, physical inactivity and diabetes mellitus. Data were analysed with Cox regression models. Measures of multiplicative and additive interaction were calculated to determine if the presence of both depressive symptoms and a risk factor amplified the risk of CVD.Results: Of all participants, 12.6% had clinically relevant depressive symptoms and, after a median follow-up of six years, 15.7% developed CVD. Only the additive interaction between physical inactivity and depressive symptoms was statistically significant and explained 40.6% of the CVD risk among inactive persons with depressive symptoms.Conclusion: In the general population, we did not detect synergistic effects for most risk factors. However, older adults with clinically relevant depressive symptoms and a physically inactive lifestyle appeared to be at a particularly high risk to develop CVD and may represent an important target for cardiovascular prevention. [ABSTRACT FROM AUTHOR]

B Background: b Frontotemporal dementia (FTD) is the second-most common cause of early onset dementia. The FTD sample consisted of behavioral variant FTD (n=206; 63.0%), progressive non-fluent aphasia (n=24; 7.3%), semantic dementia (n=75; 22.9%), FTD with motor neuron disease (n=18; 5.5%) and FTD subtype unspecified (n=4; 1.2%). [Extracted from the article]

This study examines the impact of the Dutch District Approach, a major urban regeneration programme that was started in 2008 in the Netherlands, on social, physical and mental functioning of older adults. Data from 1092 participants (58-93 years at baseline) across two waves (2005/06 and 2011/12) of the Longitudinal Aging Study Amsterdam were linked to detailed data on exposure to the programme. Using a difference-in-difference approach, we assessed differences from pre-intervention to the intervention period between the target and control districts in loneliness, social engagement, social isolation, physical activity, and anxiety and depressive symptoms. Regardless of programme intensity, the results indicate that the Dutch District Approach did not benefit or harm these aspects of functioning in older adults. [ABSTRACT FROM AUTHOR]

Very few studies looking at slow gait speed as early marker of cognitive decline investigated the competing risk of death. The current study examines associations between slow gait speed and transitions between cognitive states and death in later life. We performed a coordinated analysis of three longitudinal studies with 9 to 25 years of follow-up. Data were used from older adults participating in H70 (Sweden; n = 441; aged ≥70 years), InCHIANTI (Italy; n = 955; aged ≥65 years), and LASA (the Netherlands; n = 2824; aged ≥55 years). Cognitive states were distinguished using the Mini-Mental State Examination. Slow gait speed was defined as the lowest sex-specific quintile at baseline. Multistate models were performed, adjusted for age, sex and education. Most effect estimates pointed in the same direction, with slow gait speed predicting forward transitions. In two cohort studies, slow gait speed predicted transitioning from mild to severe cognitive impairment (InCHIANTI: HR = 2.08, 95%CI = 1.40–3.07; LASA: HR = 1.33, 95%CI = 1.01–1.75) and transitioning from a cognitively healthy state to death (H70: HR = 3.30, 95%CI = 1.74–6.28; LASA: HR = 1.70, 95%CI = 1.30–2.21). Screening for slow gait speed may be useful for identifying older adults at risk of adverse outcomes such as cognitive decline and death. However, once in the stage of more advanced cognitive impairment, slow gait speed does not seem to predict transitioning to death anymore. • There has been an increasing interest in slow gait speed as risk factor for cognitive decline. • Very few studies have investigated the competing risk of death. • This study shows that slow gait speed predicts transitions into cognitive impairment and death. • Once in the stage of more advanced cognitive impairment, slow gait does not predict death anymore. [ABSTRACT FROM AUTHOR]

Genetic factors play a major role in frontotemporal dementia (FTD). The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered. Common variants have been identified with genome-wide association studies (GWAS), but these studies have not systematically searched for rare variants. To identify rare and new common variant FTD risk loci and provide more insight into the heritability of C9ORF72-related FTD, we performed a GWAS consisting of 354 FTD patients (including and excluding N = 28 pathological repeat carriers) and 4209 control subjects. The Haplotype Reference Consortium was used as reference panel, allowing for the imputation of rare genetic variants. Two rare genetic variants nearby C9ORF72 were strongly associated with FTD in the discovery (rs147211831: OR = 4.8, P = 9.2 × 10 -9 , rs117204439: OR = 4.9, P = 6.0 × 10 -9 ) and replication analysis (P < 1.1 × 10 -3 ). These variants also significantly associated with amyotrophic lateral sclerosis in a publicly available dataset. Using haplotype analyses in 1200 individuals, we showed that these variants tag a sub-haplotype of the founder haplotype of the repeat expansion that was previously found to be present in virtually all pathological C9ORF72 G 4 C 2 repeat lengths. This new risk haplotype was 10 times more likely to contain a C9ORF72 pathological repeat length compared to founder haplotypes without one of the two risk variants (~22% versus ~2%; P = 7.70 × 10 -58 ). In haplotypes without a pathologic expansion, the founder risk haplotype had a higher number of repeats (median = 12 repeats) compared to the founder haplotype without the risk variants (median = 8 repeats) (P = 2.05 × 10 -260 ). In conclusion, the identified risk haplotype, which is carried by ~4% of all individuals, is a major risk factor for pathological repeat lengths of C9ORF72 G 4 C 2 . These findings strongly indicate that longer C9ORF72 repeats are unstable and more likely to convert to germline pathological C9ORF72 repeat expansions., (© 2021. The Author(s).)

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.