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Public Health.
(2024-12) Röhr S; Gibson R; Alpass F
BACKGROUND: High purpose in life - the extent of engagement in activities that are personally valued and give a sense of direction and meaning to life - has been associated with higher cognitive functioning and may protect against dementia. Less is known about gender differences in cognitive functioning regarding purpose in life. Understanding gender-specific links can inform tailored interventions aimed at promoting cognitive health. METHOD: A subsample (n = 875, aged 50-85 years) of the NZHWR study completed face-to-face cognitive assessments and postal surveys in 2012. Cognitive functioning was assessed with Addenbrooke's Cognitive Examination-Revised (ACE-R), adapted for culturally acceptable use in New Zealand. Purpose in life was measured with the Life Engagement Test. Linear regression analysis assessed associations of gender, purpose in life and their interaction with cognitive functioning, controlling for socioeconomic factors (age, age², education, ethnicity [Māori, Indigenous people of New Zealand, and Non-Māori, mostly of European descent], marital status, employment, individual-level economic hardship, area-based socioeconomic deprivation), lifestyle and health factors (smoking, alcohol consumption, physical activity, SF-12 physical and mental health, social engagement, social loneliness). RESULT: The analytical sample (n = 643) was M = 65.3 (SD = 7.4) years old; 53.3% women, 21.2% Māori. The ACE-R score was M = 92.9 (SD = 5.3). N = 55 (8.5%) scored ≥1.5SD below the mean, indicating cognitive impairment. Women had higher cognitive functioning (M = 93.7, SD = 4.6 vs. M = 92.0, SD = 5.8; Z = -3.88, p<.001) and purpose in life (M = 26.2, SD = 3.8 vs. M = 25.8, SD = 3.4; Z = -2.19, p = .029) than men. In the adjusted regression analysis (R² = 27.6%), higher purpose in life (B = 0.29, 95%CI = 0.12;0.46; p = .001) and female gender (B = 9.97, 95%CI = 4.71;15.24, p<.001) were associated with higher cognitive functioning. The association of purpose in life with cognitive functioning was less pronounced for women than men (B = -0.31, 95%CI = -0.51;-0.11; p = .003) (Fig. 1). Significant covariates included age², education, deprivation, and social loneliness. CONCLUSION: In this sample of older New Zealanders, a gender difference in cognitive functioning varied by level of purpose in life. Women had higher cognitive functioning than men, particularly at lower purpose in life, with the difference decreasing as purpose in life increases. Interventions to enhance purpose in life might particularly benefit men. Notably, cognitive functioning may also impact purpose in life, emphasising the need for longitudinal studies.
Area-based socioeconomic deprivation is associated with cognitive decline in midlife to early late-life New Zealanders without cognitive impairment
(Wiley Periodicals LLC on behalf of Alzheimer's Association, 2025-01-09) Röhr S; Gibson R; Alpass F
Background Research identified individual-level socioeconomic factors as key determinants of cognitive health. This study investigated the effect of area-based socioeconomic deprivation on cognitive outcomes in midlife to early late-life New Zealanders without cognitive impairment. Understanding geographical dimensions of socioeconomic determinants of cognitive health is important from an equity perspective. Method Data stemmed from a subsample of the New Zealand Health, Work and Retirement Study, a cohort study on ageing. In 2010, 1,001 participants aged 49-84 years completed face-to-face interviews and were reassessed two years later. Cognitive functioning was measured using Addenbrooke’s Cognitive Examination–Revised, adapted for culturally acceptable use in New Zealand. Area-based socioeconomic deprivation was assessed using the New Zealand Deprivation Index (NZDep2006). Linear mixed-effects models analysed the association between area-based socioeconomic deprivation and cognitive outcomes, controlling for individual-level socioeconomic (age, age², gender, education, ethnicity [Māori, Indigenous people of New Zealand, and Non-Māori, mostly of European descent], marital status, employment, net personal income), lifestyle and health variables (Lifestyle for Brain Health/LIBRA index, social loneliness). Result The analysis included 783 participants (54.7% female, mean age 62.7 years, 25.0% Māori). Individuals with cognitive impairment at baseline (n = 69) and older than 75 years were excluded (n = 79). Further attrition was due to missing data. At baseline, 39.7% resided in low deprivation areas, 39.0% in moderate, and 21.3% in high deprivation areas. The unadjusted model indicated a significant association between higher area-based socioeconomic deprivation and lower cognitive functioning (B = -0.16, 95%CI: -0.22,-0.10; p < .001) and cognitive decline (B = -0.12, 95%CI: -0.21;-0.03; p = .015). The adjusted model yielded similar results for cognitive functioning (B = -0.08, 95%CI: -0.15;-0.01; p = .050) and cognitive decline (B = -0.12, 95%CI: -0.20;-0.04, p = .013) (Fig. 1). Influential covariates included gender, education, and lifestyle (LIBRA). Conclusion This study demonstrated a relationship between higher area-based socioeconomic deprivation and lower cognitive functioning, along with cognitive decline, in cognitively unimpaired New Zealanders aged 48 to 75 years. These findings emphasize the importance of considering neighbourhood characteristics and broader socioeconomic factors in strategies aimed at mitigating cognitive health disparities and reducing the impact of dementia in disadvantaged communities.
Depression and anxiety at 1- and 12-months post ischemic stroke: methods for examining individual change over time.
(CSIRO Publishing on behalf of the Australasian Society for the Study of Brain Impairment, 2024-12-05) Barker-Collo S; Krishnamurthi R; Nair B; Ranta A; Douwes J; Feigin V; Honan C
Background Depression is commonly studied post stroke, while anxiety is less studied. This study presents prevalence of depression and anxiety at 1- and 12-months post ischemic stroke alongside three methods for examining within-subjects change over time. Methods Participants were ischemic stroke patients of the Auckland Regional Community Stroke Study (ARCOS-V) with Hospital Anxiety and Depression Scale data at 1- (n = 343) and 12-months (n = 307). Change over time was examined using within-subjects repeated measures ANOVA, calculation of the Reliable Change Index, and a Sankey diagram of those meeting cut-off scores (>7) for caseness over time. Results Using repeated measures ANOVA, depression scores didn’t change significantly over time, while anxiety symptoms decreased significantly. When reliable change was calculated, 4.2% of individuals had reliable decreases in anxiety symptoms, while 5.7% had reliable decreases in depression symptoms. Those who had a reliable decrease in one tended to have a reliable decrease in the other. In the Sankey, the proportion of those meeting the cut-off score for anxiety did not change over time (12.8 and 12.7% at 1- and 12-months), while those meeting the cut-off for depression increased slightly (3.7–4.5%) and those meeting cut-offs for both decreased from 10.4 to 8.1%. Conclusion The three methods produced very different findings. Use of cut-off scores is common but has limitations. Calculation of clinically reliable change is recommended. Further work is needed to ensure depression and anxiety are monitored over time post-stroke, and both should be the subject of intervention efforts in both acute and late stages post-stroke.
Trajectory of Cognitive Decline Before and After Stroke in 14 Population Cohorts
(American Medical Association, 2024-10-02) Lo JW; Crawford JD; Lipnicki DM; Lipton RB; Katz MJ; Preux P-M; Guerchet M; d'Orsi E; Quialheiro A; Rech CR; Ritchie K; Skoog I; Najar J; Sterner TR; Rolandi E; Davin A; Rossi M; Riedel-Heller SG; Pabst A; Röhr S; Ganguli M; Jacobsen E; Snitz BE; Anstey KJ; Aiello AE; Brodaty H; Kochan NA; Chen Y-C; Chen J-H; Sanchez-Juan P; Del Ser T; Valentí M; Lobo A; De-la-Cámara C; Lobo E; Sachdev PS
IMPORTANCE: Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear. OBJECTIVE: To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajectory prestroke in stroke survivors with the trajectory of individuals without incident stroke over follow-up. DESIGN, SETTING, AND PARTICIPANTS: The study used harmonized and pooled data from 14 population-based cohort studies included in the Cohort Studies of Memory in an International Consortium collaboration. These studies were conducted from 1993 to 2019 across 11 countries among community-dwelling older adults without a history of stroke or dementia. For this study, linear mixed-effects models were used to estimate trajectories of cognitive function poststroke relative to a stroke-free cognitive trajectory. The full model adjusted for demographic and vascular risk factors. Data were analyzed from July 2022 to March 2024. EXPOSURE: Incident stroke. MAIN OUTCOMES AND MEASURES: The primary outcome was global cognition, defined as the standardized average of 4 cognitive domains (language, memory, processing speed, and executive function). Cognitive domain scores were formed by selecting the most commonly administered test within each domain and standardizing the scores. RESULTS: The study included 20 860 participants (12 261 [58.8%] female) with a mean (SD) age of 72.9 (8.0) years and follow-up of 7.51 (4.2) years. Incident stroke was associated with a substantial acute decline in global cognition (-0.25 SD; 95% CI, -0.33 to -0.17 SD), the Mini-Mental State Examination, and all cognitive domains (ranging from -0.17 SD to -0.22 SD), as well as accelerated decline in global cognition (-0.038 SD per year; 95% CI, -0.057 to -0.019 SD per year) and all domains except memory (ranging from -0.020 to -0.055 SD per year), relative to a stroke-free cognitive trajectory. There was no significant difference in prestroke slope in stroke survivors compared with the rate of decline in individuals without stroke in all cognitive measures. The mean rate of decline without a previous stroke was -0.049 SD per year (95% CI, -0.051 to -0.047 SD) in global cognition. CONCLUSIONS AND RELEVANCE: In this cohort study using pooled data from 14 cohorts, incident stroke was associated with acute and accelerated long-term cognitive decline in older stroke survivors.
Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities
(Springer Nature Limited, 2019-12-20) Migliavacca E; Tay SKH; Patel HP; Sonntag T; Civiletto G; McFarlane C; Forrester T; Barton SJ; Leow MK; Antoun E; Charpagne A; Seng Chong Y; Descombes P; Feng L; Francis-Emmanuel P; Garratt ES; Giner MP; Green CO; Karaz S; Kothandaraman N; Marquis J; Metairon S; Moco S; Nelson G; Ngo S; Pleasants T; Raymond F; Sayer AA; Ming Sim C; Slater-Jefferies J; Syddall HE; Fang Tan P; Titcombe P; Vaz C; Westbury LD; Wong G; Yonghui W; Cooper C; Sheppard A; Godfrey KM; Lillycrop KA; Karnani N; Feige JN
The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD+ levels through perturbed NAD+ biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.
Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori.
(Springer Nature, 2018-03-27) Hakkaart C; Ellison-Loschmann L; Day R; Sporle A; Koea J; Harawira P; Cheng S; Gray M; Whaanga T; Pearce N; Guilford P
New Zealand Māori have a considerably higher incidence of gastric cancer compared to non-Māori, and are one of the few populations worldwide with a higher prevalence of diffuse-type disease. Pathogenic germline CDH1 mutations are causative of hereditary diffuse gastric cancer, a cancer predisposition syndrome primarily characterised by an extreme lifetime risk of developing diffuse gastric cancer. Pathogenic CDH1 mutations are well described in Māori families in New Zealand. However, the contribution of these mutations to the high incidence of gastric cancer is unknown. We have used next-generation sequencing, Sanger sequencing, and Multiplex Ligation-dependent Probe Amplification to examine germline CDH1 in an unselected series of 94 Māori gastric cancer patients and 200 healthy matched controls. Overall, 18% of all cases, 34% of cases diagnosed with diffuse-type gastric cancer, and 67% of cases diagnosed aged less than 45 years carried pathogenic CDH1 mutations. After adjusting for the effect of screening known HDGC families, we estimate that 6% of all advanced gastric cancers and 13% of all advanced diffuse-type gastric cancers would carry germline CDH1 mutations. Our results demonstrate that germline CDH1 mutations are a significant contributor to the high frequency of diffuse gastric cancer in New Zealand Māori.
Severe weather events and cryptosporidiosis in Aotearoa New Zealand: A case series of space-time clusters.
(Cambridge University Press, 2024-04-15) Grout L; Hales S; Baker MG; French N; Wilson N
Occurrence of cryptosporidiosis has been associated with weather conditions in many settings internationally. We explored statistical clusters of human cryptosporidiosis and their relationship with severe weather events in New Zealand (NZ). Notified cases of cryptosporidiosis from 1997 to 2015 were obtained from the national surveillance system. Retrospective space-time permutation was used to identify statistical clusters. Cluster data were compared to severe weather events in a national database. SaTScan analysis detected 38 statistically significant cryptosporidiosis clusters. Around a third (34.2%, 13/38) of these clusters showed temporal and spatial alignment with severe weather events. Of these, nearly half (46.2%, 6/13) occurred in the spring. Only five (38%, 5/13) of these clusters corresponded to a previously reported cryptosporidiosis outbreak. This study provides additional evidence that severe weather events may contribute to the development of some cryptosporidiosis clusters. Further research on this association is needed as rainfall intensity is projected to rise in NZ due to climate change. The findings also provide further arguments for upgrading the quality of drinking water sources to minimize contamination with pathogens from runoff from livestock agriculture.
Identifying important microbial and genomic biomarkers for differentiating right- versus left-sided colorectal cancer using random forest models
(BioMed Central Ltd, 2023-07-11) Kolisnik T; Sulit AK; Schmeier S; Frizelle F; Purcell R; Smith A; Silander O
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease, with subtypes that have different clinical behaviours and subsequent prognoses. There is a growing body of evidence suggesting that right-sided colorectal cancer (RCC) and left-sided colorectal cancer (LCC) also differ in treatment success and patient outcomes. Biomarkers that differentiate between RCC and LCC are not well-established. Here, we apply random forest (RF) machine learning methods to identify genomic or microbial biomarkers that differentiate RCC and LCC. METHODS: RNA-seq expression data for 58,677 coding and non-coding human genes and count data for 28,557 human unmapped reads were obtained from 308 patient CRC tumour samples. We created three RF models for datasets of human genes-only, microbes-only, and genes-and-microbes combined. We used a permutation test to identify features of significant importance. Finally, we used differential expression (DE) and paired Wilcoxon-rank sum tests to associate features with a particular side. RESULTS: RF model accuracy scores were 90%, 70%, and 87% with area under curve (AUC) of 0.9, 0.76, and 0.89 for the human genomic, microbial, and combined feature sets, respectively. 15 features were identified as significant in the model of genes-only, 54 microbes in the model of microbes-only, and 28 genes and 18 microbes in the model with genes-and-microbes combined. PRAC1 expression was the most important feature for differentiating RCC and LCC in the genes-only model, with HOXB13, SPAG16, HOXC4, and RNLS also playing a role. Ruminococcus gnavus and Clostridium acetireducens were the most important in the microbial-only model. MYOM3, HOXC4, Coprococcus eutactus, PRAC1, lncRNA AC012531.25, Ruminococcus gnavus, RNLS, HOXC6, SPAG16 and Fusobacterium nucleatum were most important in the combined model. CONCLUSIONS: Many of the identified genes and microbes among all models have previously established associations with CRC. However, the ability of RF models to account for inter-feature relationships within the underlying decision trees may yield a more sensitive and biologically interconnected set of genomic and microbial biomarkers.
Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study
(Public Library of Science (PLoS), 2019-07) Lipnicki DM; Makkar SR; Crawford JD; Thalamuthu A; Kochan NA; Lima-Costa MF; Castro-Costa E; Ferri CP; Brayne C; Stephan B; Llibre-Rodriguez JJ; Llibre-Guerra JJ; Valhuerdi-Cepero AJ; Lipton RB; Katz MJ; Derby CA; Ritchie K; Ancelin M-L; Carrière I; Scarmeas N; Yannakoulia M; Hadjigeorgiou GM; Lam L; Chan W-C; Fung A; Guaita A; Vaccaro R; Davin A; Kim KW; Han JW; Suh SW; Riedel-Heller SG; Roehr S; Pabst A; van Boxtel M; Köhler S; Deckers K; Ganguli M; Jacobsen EP; Hughes TF; Anstey KJ; Cherbuin N; Haan MN; Aiello AE; Dang K; Kumagai S; Chen T; Narazaki K; Ng TP; Gao Q; Nyunt MSZ; Scazufca M; Brodaty H; Numbers K; Trollor JN; Meguro K; Yamaguchi S; Ishii H; Lobo A; Lopez-Anton R; Santabárbara J; Leung Y; Lo JW; Popovic G; Sachdev PS; for Cohort Studies of Memory in an International Consortium (COSMIC)
Background With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54–105 (mean = 72.7) years and without dementia at baseline. Studies had 2–15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = −0.1, SE = 0.01), APOE*4 carriage (B = −0.31, SE = 0.11), depression (B = −0.11, SE = 0.06), diabetes (B = −0.23, SE = 0.10), current smoking (B = −0.20, SE = 0.08), and history of stroke (B = −0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = −0.07, SE = 0.01), APOE*4 carriage (B = −0.41, SE = 0.18), and diabetes (B = −0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = −0.24, SE = 0.12), and between diabetes and cognitive decline (B = −0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. Conclusions These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.
Gender-specific design and effectiveness of non-pharmacological interventions against cognitive decline and dementia–protocol for a systematic review and meta-analysis
(Public Library of Science (PLoS), 2021-08-27) Zuelke AE; Riedel-Heller SG; Wittmann F; Pabst A; Roehr S; Luppa M
Introduction Dementia is a public health priority with projected increases in the number of people living with dementia worldwide. Prevention constitutes a promising strategy to counter the dementia epidemic, and an increasing number of lifestyle interventions has been launched aiming at reducing risk of cognitive decline and dementia. Gender differences regarding various modifiable risk factors for dementia have been reported, however, evidence on gender-specific design and effectiveness of lifestyle trials is lacking. Therefore, we aim to systematically review evidence on gender-specific design and effectiveness of trials targeting cognitive decline and dementia. Methods and analysis We will conduct a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases MEDLINE (PubMed interface), PsycINFO, Web of Science Core Collection, Cochrane Central Register of Controlled Trials (CENTRAL) and ALOIS will be searched for eligible studies using a predefined strategy, complemented by searches in clinical trials registers and Google for grey literature. Studies assessing cognitive function (overall measure or specific subdomains) as outcome in dementia-free adults will be included, with analyses stratified by level of cognitive functioning at baseline: a) cognitively healthy b) subjective cognitive decline 3) mild cognitive impairment. Two reviewers will independently evaluate eligible studies, extract data and determine methodological quality using the Scottish Intercollegiate Guidelines Network (SIGN)-criteria. If sufficient data with regards to quality and quantity are available, a meta-analysis will be conducted. Ethics and dissemination No ethical approval will be required as no primary data will be collected. PROSPERO registration number CRD42021235281.

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