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1.
Curr Alzheimer Res ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33583381

RESUMO

BACKGROUND: The interaction between cerebral vessel disease (CVD) pathology and Alzheimer's disease (AD) pathology in the development of dementia is controversial. We examined the association of cerebral vascular neuropathology and cerebrovascular risk factors with the mild stage of Alzheimer's dementia and cognitive function. METHODS: This cross-sectional study included men and women aged 60 years or over who had yearly clinical assessments and had agreed to brain autopsy at the time of death, and who contributed to data stored at the National Alzheimer's Coordinating Center (NACC) in the USA. Cognitively normal and impaired subjects with presumptive aetiology of AD, including mild cognitive impairment (ADMCI) and dementia (Alzheimer's dementia), and with complete neuropathological data, were included in our analyses. We used neuropsychological data proximate to death to create summary measures of global cognition and cognitive domains. Systematic neuropathological assessments documenting the severity of cerebral vascular pathology were included. Logistic and linear regression analyses corrected for age at death, sex and Lewy body pathology were used to examine associations of vessel disease with the severity of Alzheimer's disease dementia, and cognitive function, respectively. RESULTS: No significant relationship was observed between late-life risk factors and Alzheimer's dementia. The severity of arteriosclerosis and presence of global infarcts/lacunes were related to mild Alzheimer's dementia (B=0.423, p<0.001;B=0.366, p=0.026), and the effects were significant after adjusting for neuritic plaques and neurofibrillary tangles (B=0.385, p<0.001;B=0.63, p=0.001). When vascular brain injuries were subdivided into old and acute/subacute types, we found that old microinfarcts and old microbleeds were associated with mild Alzheimer's dementia (B=0.754, p=0.007; B=2.331, p=0.032). The old microinfarcts remained significantly associated with mild Alzheimer's dementia after correcting AD pathologies (B=1.31, p<0.001). In addition, the number of microinfarcts in the cerebral cortex had a significant relation with mild Alzheimer's dementia, whether or not the data were corrected for AD pathologies (B=0.616, p=0.016; B=0.884, p=0.005). Atherosclerosis, arteriosclerosis and white matter rarefaction were found to be significantly associated with faster progression of Alzheimer's dementia (B=0.068, p=0.001; B=0.046, p=0.016, B=0.081, p=0.037), but white matter rarefaction no longer had a significant effect after adjusting for AD pathologies. We also found that the severity of atherosclerosis was related to impairment in processing speed (ß=-0.112, p=0.006) and executive function (ß=-0.092, p=0.023). Arteriosclerosis was significantly associated with language (ß=-0.103, p=0.011) and global cognition (ß=-0.098, p=0.016) deficits. CONCLUSION: Our study found the significant relation of global, old, acute/subacute and regional cerebral vascular pathologies, but not white matter rarefaction, to the onset and severity of Alzheimer's dementia. We also showed that late-life risk factors were found to have no relation with Alzheimer's dementia, and the increased risk of dementia with APOE ε4 is not mediated by CVD. The best interpretation of these findings is that CVD has an additive effect with AD pathologies in the development and progression of what is clinically diagnosed as Alzheimer's dementia, and it is very likely that CVD and AD are to a major degree independent pathologies.

2.
BMJ Open ; 11(2): e038624, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563617

RESUMO

OBJECTIVES: Conducting a national survey of clinicians and administrators from specialised dementia assessment services (memory clinics) in Australia to examine their current organisational aspects and assessment procedures and inform clinical tool harmonisation as part of the Australian Dementia Network-memory clinics project. DESIGN: A cross-sectional survey. SETTING: Public and private memory clinics across Australia. PARTICIPANTS: 150 individual clinicians completed the survey between May and August 2019. Responses could be given anonymously. Most clinics were publicly funded services (83.2%) and in metropolitan regions (70.9%). OUTCOME MEASURES: Descriptive data on organisational aspects of memory clinics (eg, waiting times, staffing); the three most commonly used assessment tools per assessment type (eg, self-report) and cognitive domain (eg, attention). RESULTS: Since the last national survey in 2009, the number of memory clinics across Australia has increased substantially but considerable variability has remained with respect to funding structure, staffing and assessment procedures. The average clinic employed 2.4 effective full-time staff (range 0.14-14.0). The reported waiting time for an initial assessment ranged from 1 week to 12 months with a median of 7 weeks. While most clinics (97%) offered follow-up assessments for their clients, only a few (31%) offered any form of cognitive intervention. We identified over 100 different cognitive assessment tools that were used at least 'sometimes', with widespread use of well-established core screening tools and a subset of common neuropsychological tests. CONCLUSION: This paper presents a current snapshot of Australian memory clinics, showing considerable heterogeneity with some common core elements. These results will inform the development of national memory clinic guidelines. Furthermore, our data make a valuable contribution to the international comparison of clinical practice standards and advocate for greater harmonisation to ensure high-quality dementia care.

3.
Neurology ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504642

RESUMO

OBJECTIVE: To determine if severe perivascular space (PVS) dilation is associated with longitudinal cognitive decline and incident dementia over four and eight years respectively, we analyzed data from a prospective cohort study. METHODS: 414 community dwelling older adults aged 72-92 were assessed at baseline and biennially for up to eight years, with cognitive assessments, consensus dementia diagnoses and 3T MRI imaging. The numbers of PVS in two representative slices in the basal ganglia (BG) and centrum semiovale (CSO) were counted and severe PVS pathology defined as the top quartile. The effects of severe PVS pathology in i) either region; ii) both regions; and those with iii) severe BG PVS and iv) severe CSO PVS were examined. White matter hyperintensity volume, cerebral microbleed number and lacune number were calculated. RESULTS: Participants with severe PVS pathology in both regions or in the CSO alone had greater decline in global cognition over four years, even after adjustment for the presence of other small vessel disease neuroimaging markers. The presence of severe PVS pathology in both regions was an independent predictor of dementia across eight years (OR 2.91, 95%CI 1.43-5.95, p= 0.003). Further, the presence of severe PVS pathology in all groups examined was associated with greater dementia risk at either year four or six. CONCLUSIONS: Severe PVS pathology is a marker for increased risk of cognitive decline and dementia, independent of other small vessel disease markers. The differential cognitive associations for BG and CSO PVS may represent differences in their underlying pathology.

4.
Curr Opin Psychiatry ; 34(2): 142-148, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395097

RESUMO

PURPOSE OF REVIEW: The relationship between hypertension and Alzheimer's disease (AD) is complex and varies across the lifespan. Studies have suggested that midlife hypertension is a risk factor for AD, although studies of late life hypertension have suggested that it either has no effect or a weak protective effect. RECENT FINDINGS: Animal models of induced and spontaneous hypertension have found that AD pathological change (ß-amyloid plaques and tau tangles) occurs within weeks of a hypertensive insult. Human imaging and autopsy studies indicate that midlife and late life hypertension are associated with increased AD pathological change. Meta-analyses of longitudinal studies indicate that midlife rather than late life hypertension is a risk factor for AD. New areas of research have suggested that rather than mean blood pressure (BP), it is the negative BP trajectories or the variability of BP that contributes to AD. In a number of meta-analyses of antihypertensive medications and their effect on AD, there were weak associations between improved AD outcomes and treatment. SUMMARY: The combined analysis of animal, human clinical/pathological, epidemiological and drug trial data indicates that hypertension increases the risk of AD and treatment of hypertension may be an appropriate preventive measure.

5.
Neurobiol Aging ; 98: 108-115, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33259984

RESUMO

Hippocampal volume is an important biomarker of Alzheimer's disease (AD), and genetic risk of AD is associated with hippocampal atrophy. However, the hippocampus is not a uniform structure and has a number of subfields, the associations of which with age, sex, and polygenic risk score for AD (PRSAD) have been inadequately investigated. We examined these associations in 17,161 cognitively normal UK Biobank participants (44-80 years). Age was negatively associated with all the hippocampal subfield volumes and females had smaller volumes than men. Higher PRSAD was associated with lower volumes in the bilateral whole hippocampus, hippocampal-amygdala-transition-area, and hippocampal tail; right subiculum; left cornu ammonis 1, cornu ammonis 4, molecular layer, and granule cell layer of dentate gyrus. Older individuals (median age 63 years, n = 8984) showed greater subfield vulnerability to high PRSAD compared to the younger group (n = 8177), but the effect did not differ by sex. The pattern of subfield involvement in relation to the PRSAD in community dwelling healthy individuals sheds additional light on the pathogenesis of AD.

6.
Alzheimers Res Ther ; 12(1): 167, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33339532

RESUMO

BACKGROUND: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. METHODS: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. RESULTS: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. CONCLUSIONS: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33225353

RESUMO

BACKGROUND: While midlife hypertension is deleterious, late-life hypertension has been associated with better cognitive outcomes in several studies. Many questions remain, including the relative benefit or harm of a blood pressure (BP) target and antihypertensive therapy of <120 in very old individuals. METHODS: The Sydney Memory and Aging Study (n = 1015) comprises a cohort of 70- to 90-year-olds, who were followed biennially for 8 years. Global cognition was assessed with a battery of 10 neuropsychological tests. Blood pressure was measured at Waves 1 and 2 and classified into 3 systolic groupings: group 1 (≤120 mmHg), group 2 (121-140 mmHg), and group 3 (>140 mmHg). Multiple regression, linear mixed modeling, and Cox regression examined the effect of BP and antihypertensives. RESULTS: There were no overall significant differences in global cognition or dementia between the disparate BP groups. However, in those not taking antihypertensives, the systolic BP (SBP) > 140 mmHg group had a significantly worse global cognitive trajectory compared to SBP ≤ 120 mmHg (b = -0.067, 95% CI [-0.129, -0.006], p = .030). Within the SBP ≤ 120 mmHg group those taking antihypertensives had significantly worse global cognition trajectories compared to those not taking antihypertensives even when controlling for past history of hypertension (b = -0.077, 95% CI [-0.147, -0.007], p = .030). CONCLUSIONS: Untreated hypertension in old age is related to worse global cognitive decline. However, ongoing treatment at new recommendations of lower SBP targets may be related to poorer cognitive decline and should be considered carefully in older populations.

8.
Neurobiol Aging ; 97: 97-105, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33190123

RESUMO

Understanding heterogeneity in brain aging trajectories is important to estimate the extent to which aging outcomes can be optimized. Although brain changes in late life are well-characterized, brain changes in middle age are not well understood. In this study, we investigated hippocampal change in a generally healthy community-living population of middle (n = 421, mean age 47.2 years) and older age (n = 411, mean age 63.0 years) individuals, over a follow-up of up to 12 years. Manually traced hippocampal volumes were analyzed using multilevel models and latent class analysis to investigate longitudinal aging trajectories and laterality and sex effects, and to identify subgroups that follow different aging trajectories. Hippocampal volumes decreased on average by 0.18%/year in middle age and 0.3%/year in older age. Men tended to experience steeper declines than women in middle age only. Three subgroups of individuals following different trajectories were identified in middle age and 2 in older age. Contrary to expectations, the subgroup containing two-thirds of older age participants maintained stable hippocampal volumes across the follow-up.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33159521

RESUMO

OBJECTIVES: This study assessed whether reciprocal relationships exist between cognitive function and the social network size of older adults, controlling for age, sex, education, medical conditions, and depressive symptoms. METHOD: Data were collected at biennial follow-ups over six years in the Sydney Memory and Ageing study, a longitudinal cohort study including 1037 community-based Sydney residents age 70 to 90 years without dementia at baseline. We used random intercept cross-lagged panel models to investigate reciprocal associations between social network size and scores in each of seven cognitive domains including a global score. RESULTS: Standardized models indicated that within-person deviation in expected language score predicted deviation in expected network size. Within-person deviation in prior expected social network size predicted deviation in expected executive function at year six. Cross-lagged effects in models of both global cognition and memory, respectively, could not be attributed solely to within-person change. DISCUSSION: Findings support a co-constitutive view of cognitive function and social relationships in older age. Although both cognition and network size declined over time, slower than expected decline in language ability predicted less than expected contraction in social networks. Similar influence of network size on executive functioning indicated that relationships with friends and family outside of the home contributed significantly to maintenance of higher order cognitive abilities in older late life. Diverse patterns of influence between cognitive domains and social network size over six years underscore the importance of assessing the complex and nuanced interplay between brain health and social relationships in older age.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33253696

RESUMO

OBJECTIVE: To determine whether impairments across cognitive and affective domains provide additional information to sensorimotor deficits for fall prediction amongst various populations. DESIGN: We pooled data from five studies for this observational analysis of prospective falls. SETTING: Community or low-level care facility. PARTICIPANTS: A total of 1,090 older people (74.0±9.4 years;579♀); 500 neurologically intact (NI) older people and three groups with neurological disorders (cognitive impairment, N=174; multiple sclerosis (MS), N=111; Parkinson's disease, N=305). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Sensorimotor function was assessed with the Physiological Profile Assessment, cognitive function with tests of executive function, affect with questionnaires of depression, and concern about falling with falls efficacy questionnaires. These variables were associated with fall incidence rates, obtained prospectively over 6-12 months. RESULTS: Poorer sensorimotor function was associated with falls (incidence rate ratio[95% confidence interval]: 1.46[1.28-1.66]). Impaired executive function was the strongest predictor of falls overall (2.91[2.27-3.73]), followed by depressive symptoms (2.07[1.56-2.75)] and concern about falling (2.02[1.61-2.55]). Associations were similar among groups, except for a weaker relationship with executive impairment in NI and a stronger relationship with concern about falling in MS. Multivariable analyses showed that executive impairment, poorer sensorimotor performance, depressive symptoms and concern about falling were independently associated with falls. CONCLUSIONS: Deficits in cognition (executive function) and affect (depressive symptoms) and concern about falling are as important as sensorimotor function for fall prediction. These domains should be included in fall risk assessments for older people and clinical groups.

11.
Eat Weight Disord ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051857

RESUMO

PURPOSE: Anorexia nervosa (AN) affects approximately 2.9% of females and has the highest mortality rate among all psychiatric disorders. Despite several advances, the neurobiology of this disorder is still not well understood. Several studies have reported abnormalities in the white matter, but it is not know if these are disease-related or secondary to undernutrition. This study aimed to further our understanding of white matter pathology using diffusion-weighted imaging in underweight adolescents with AN, and to examine changes occurring after short-term weight restoration. METHODS: Analyses were conducted on diffusion-weighted imaging from 24 female adolescents with AN and 17 age- and gender-matched healthy controls (HC), aged 14-19 years. Groups were compared on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) using tract-based spatial statistics analysis and DTI measures were correlated with eating disorder examination questionnaire (EDE-Q) subscales and body mass index (BMI). Preliminary repeated-measure analyses were also conducted on eight participants after short-term weight restoration (median 41 days). RESULTS: Widespread increases in MD of up to 9% were found in underweight AN relative to HC, particularly in the corpus callosum. This was associated with both increased AD and RD, suggestive of dys- or de-myelination. There were no significant group differences in FA, and no significant correlations between DTI measures, BMI or EDE-Q subscale score. Weight restoration therapy significantly reduced MD, to levels significantly lower than HC, but did not consistently alter FA across individuals. CONCLUSIONS: White matter microstructure is significantly altered in female adolescents with AN, with preliminary longitudinal data suggesting that it may be reversible with short-term weight restoration. LEVEL OF EVIDENCE: Level III: evidence obtained from well-designed cohort or case-control analytic studies.

12.
Age Ageing ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33095852

RESUMO

BACKGROUND: This study aimed to develop cut-points for the 30-item and 10-item Iconographical Falls Efficacy Scale (IconFES) in community-dwelling older people and evaluate the psychometric properties, including construct and predictive validity with respect to falls and reduced physical activity over 1 year. METHODS: Eight hundred and one participants completed the IconFES and underwent physical, psychological and cognitive measures at baseline. Physical activity was recorded at baseline and 12 months using an activity monitor, and 1-year fall incidence was collected using monthly falls calendars. RESULTS: Using receiver-operating characteristic curves and the Youden's index for history of falls, physiological fall risk and depressive symptoms, cut-points were defined to differentiate between low and high concern about falling (30-item: <53; 10-item: <19). For the 30-item IconFES, we additionally defined cut-points for low (≤40), moderate (41-58) and high (≥59) concern about falling. Groups based on these cut-points differed significantly: low coordinated stability, executive function and amount of daily walking, and high level of disability (30-item version) and female gender (low/high 30-item version). Although there were some inconsistencies across IconFES classifications, high concern about falling predicted having had multiple falls or multiple/injurious falls, low amount of daily walking and low movement intensity at 12 months. CONCLUSIONS: The developed IconFES cut-points were sensitive to variables associated with concern about falling and predicted fall incidence and physical activity restriction after 12 months. Applying these cut-points appears useful to identify older people with high concern about falling, who are at higher risk of falls and activity curtailment.

13.
Collabra Psychol ; 6(1)2020.
Artigo em Inglês | MEDLINE | ID: mdl-33073161

RESUMO

Early investigations of the neuroticism by conscientiousness interaction with regards to health have been promising, but to date, there have been no systematic investigations of this interaction that account for the various personality measurement instruments, varying populations, or aspects of health. The current study - the second of three - uses a coordinated analysis approach to test the impact of the neuroticism by conscientiousness interaction on the prevalence and incidence of chronic conditions. Using 15 pre-existing longitudinal studies (N > 49,375), we found that conscientiousness did not moderate the relationship between neuroticism and having hypertension (OR = 1.00,95%CI[0.98,1.02]), diabetes (OR = 1.02[0.99,1.04]), or heart disease (OR = 0.99[0.97,1.01]). Similarly, we found that conscientiousness did not moderate the prospective relationship between neuroticism and onset of hypertension (OR = 0.98,[0.95,1.01]), diabetes (OR = 0.99[0.94,1.05]), or heart disease (OR = 0.98[0.94,1.03]). Heterogeneity of effect sizes was largely nonsignificant, with one exception, indicating that the effects are consistent between datasets. Overall, we conclude that there is no evidence that healthy neuroticism, operationalized as the conscientiousness by neuroticism interaction, buffers against chronic conditions.

14.
Cell Rep ; 33(4): 108323, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33113361

RESUMO

We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10-9), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients' fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: -2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: -1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients.

15.
Clin Epigenetics ; 12(1): 158, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092643

RESUMO

BACKGROUND: DNA methylation-based biological age (DNAm age) is an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its genetic and environmental causes of variation. However, these studies are not able to provide a comprehensive view of the causes of variation over the lifespan. RESULTS: In order to investigate the genetic and environmental causes of DNAm age variation across the lifespan, we pooled genome-wide DNA methylation data for 4217 people aged 0-92 years from 1871 families. DNAm age was calculated using the Horvath epigenetic clock. We estimated familial correlations in DNAm age for monozygotic (MZ) twin, dizygotic (DZ) twin, sibling, parent-offspring, and spouse pairs by cohabitation status. Genetic and environmental variance components models were fitted and compared. We found that twin pair correlations were - 0.12 to 0.18 around birth, not different from zero (all P > 0.29). For all pairs of relatives, their correlations increased with time spent living together (all P < 0.02) at different rates (MZ > DZ and siblings > parent-offspring; P < 0.001) and decreased with time spent living apart (P = 0.02) at similar rates. These correlation patterns were best explained by cohabitation-dependent shared environmental factors, the effects of which were 1.41 (95% confidence interval [CI] 1.16 to 1.66) times greater for MZ pairs than for DZ and sibling pairs, and the latter were 2.03 (95% CI 1.13 to 9.47) times greater than for parent-offspring pairs. Genetic factors explained 13% (95% CI - 10 to 35%) of variation (P = 0.27). Similar results were found for another two epigenetic clocks, suggesting that our observations are robust to how DNAm age is measured. In addition, results for the other clocks were consistent with there also being a role for prenatal environmental factors in determining their variation. CONCLUSIONS: Variation in DNAm age is mostly caused by environmental factors, including those shared to different extents by relatives while living together and whose effects persist into old age. The equal environment assumption of the classic twin study might not hold for epigenetic aging.

16.
BMC Geriatr ; 20(1): 330, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894049

RESUMO

BACKGROUND: Dementia was identified as a priority area for the development of a Clinical Quality Registry (CQR) in Australia in 2016. The Australian Dementia Network (ADNeT) Registry is being established as part of the ADNeT initiative, with the primary objective of collecting data to monitor and enhance the quality of care and patient outcomes for people diagnosed with either dementia or Mild Cognitive Impairment (MCI). A secondary aim is to facilitate the recruitment of participants into dementia research and trials. This paper describes the Registry protocol. METHODS: The ADNeT Registry is a prospective CQR of patients newly diagnosed with either dementia or MCI. Eligible patients will be identified initially from memory clinics and individual medical specialists (e.g., geriatricians, psychiatrists and neurologists) involved in the diagnosis of dementia. Participants will be recruited using either an opt-out approach or waiver of consent based on three key determinants (capacity, person responsible, and communication of diagnosis). Data will be collected from four sources: participating sites, registry participants, carers, and linkage with administrative datasets. It is anticipated that the Registry will recruit approximately 10,000 participants by the end of 2023. The ADNeT registry will be developed and implemented to comply with the national operating principles for CQRs and governed by the ADNeT Registry Steering Committee. DISCUSSION: The ADNeT Registry will provide important data on current clinical practice in the diagnosis, treatment and care of people with dementia and MCI in Australia as well as long-term outcomes among these people. These data will help to identify variations in clinical practice and patient outcomes and reasons underlying these variations, which in turn, will inform the development of interventions to improve care and outcomes for people with dementia and MCI.

17.
Int Psychogeriatr ; : 1-18, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985398

RESUMO

OBJECTIVES: Many studies document cognitive decline following specific types of acute illness hospitalizations (AIH) such as surgery, critical care, or those complicated by delirium. However, cognitive decline may be a complication following all types of AIH. This systematic review will summarize longitudinal observational studies documenting cognitive changes following AIH in the majority admitted population and conduct meta-analysis (MA) to assess the quantitative effect of AIH on post-hospitalization cognitive decline (PHCD). METHODS: We followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria were defined to identify studies of older age adults exposed to AIH with cognitive measures. 6566 titles were screened. 46 reports were reviewed qualitatively, of which seven contributed data to the MA. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: The qualitative review suggested increased cognitive decline following AIH, but several reports were particularly vulnerable to bias. Domain-specific outcomes following AIH included declines in memory and processing speed. Increasing age and the severity of illness were the most consistent risk factors for PHCD. PHCD was supported by MA of seven eligible studies with 41,453 participants (Cohen's d = -0.25, 95% CI [-0.02, -0.49] I2 35%). CONCLUSIONS: There is preliminary evidence that AIH exposure accelerates or triggers cognitive decline in the elderly patient. PHCD reported in specific contexts could be subsets of a larger phenomenon and caused by overlapping mechanisms. Future research must clarify the trajectory, clinical significance, and etiology of PHCD: a priority in the face of an aging population with increasing rates of both cognitive impairment and hospitalization.

18.
Diabetes Care ; 43(11): 2691-2701, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32967921

RESUMO

OBJECTIVE: Type 2 diabetes (diabetes) is characterized by accelerated cognitive decline and higher dementia risk. Controversy exists regarding the impact of metformin, which is associated with both increased and decreased dementia rates. The objective of this study was to determine the association of metformin use with incident dementia and cognitive decline over 6 years in participants with diabetes compared with those not receiving metformin and those without diabetes. RESEARCH DESIGN AND METHODS: A prospective observational study was conducted of N = 1,037 community-dwelling older participants without dementia aged 70-90 years at baseline (the Sydney Memory and Ageing Study). Exclusion criteria were dementia, major neurological or psychiatric disease, or progressive malignancy. Neuropsychological testing measured cognitive function every 2 years; a battery of tests measured executive function, memory, attention/speed, language, and visuospatial function individually. These were used to determine the measure of global cognition. Incident dementia was ascertained by a multidisciplinary panel. Total brain, hippocampal, and parahippocampal volumes were measured by MRI at baseline and 2 years (n = 526). Data were analyzed by linear mixed modeling, including the covariates of age, sex, education, BMI, heart disease, hypertension, stroke, smoking, and apolipoprotein Eε4 carriage. RESULTS: Of n = 1,037, 123 had diabetes; 67 received metformin (DM+MF) and were demographically similar to those who did not (DM-noMF) and participants without diabetes (no-DM). DM+MF had significantly slower global cognition and executive function decline compared with DM-noMF. Incident dementia was significantly higher in DM-noMF compared with DM+MF (odds ratio 5.29 [95% CI 1.17-23.88]; P = 0.05). CONCLUSIONS: Older people with diabetes receiving metformin have slower cognitive decline and lower dementia risk. Large randomized studies in people with and without diabetes will determine whether these associations can be attributed to metformin.

19.
Nat Commun ; 11(1): 4799, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968074

RESUMO

Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer's disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.


Assuntos
Doença de Alzheimer/genética , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Adulto , Idade de Início , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
20.
Alzheimers Dement ; 16(11): 1544-1552, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32881298

RESUMO

INTRODUCTION: Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain. METHODS: Longitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics. RESULTS: A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates. DISCUSSION: The results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.

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