Validation and reliability of the Alzheimer’s disease-Commonwealth Scientific and Industrial Research Organisation food frequency questionnaire

Accuracy in measuring intake of dietary constituents is an important issue in studies reporting the associations between diet and chronic diseases. We modified a Commonwealth Scientific and Industrial Research Organisation (CSIRO) food frequency questionnaire (FFQ) to include foods of interest in the field of Alzheimer’s disease (AD) research. The aim of the current study was to determine the reliability and validity of the AD-CSIROFFQ in 148 cognitively normal older adults. The AD-CSIROFFQ was completed before and after completion of a four-day weighed food record. Of the 508 food and beverage items reported, 309 had sufficient consumption levels for analysis of reliability. Of the 309 items, over 78% were significantly correlated between the two questionnaire administrations (Spearman’s rank correlations). We used two additional methods to assess absolute nutrient intake agreement between the AD-CSIROFFQ and the weighed food records (Pearson’s correlation coefficients and Bland–Altman plots) and quintile rankings to measure group level agreement. The adequate correlations observed between questionnaire responses suggest that the AD-CSIROFFQ is reliable. All nutrient intakes were acceptable for ranking of individuals on a group level, whilst the agreement levels with respect to the weighed food records for 11 of the 46 nutrients show validity in terms of their individual level absolute intake. The AD-CSIROFFQ makes an important contribution to the tools available for assessing usual dietary intake in groups of older adults with respect to AD research

Dietary Patterns Associated with Alzheimer\u27s Disease and Related Chronic Disease Risk: A Review

The world’s population is growing older due to improved healthcare and nutrition. As a result, Alzheimer’s disease (AD) prevalence is rapidly increasing. The focus of the current research climate is shifting from understanding AD pathology and diagnosis to primary prevention and intervention strategies. Diet represents one potential intervention strategy accessible to all. Accumulating evidence suggests diet plays a major role in risk and development of AD and AD-related chronic diseases of the periphery like cardiovascular disease (CVD) and diabetes. This paper reviews studies that have explored the relationship between “a priori” dietary patterns, AD and AD-related chronic disease risk. The dietary patterns we will review are the healthy eating index, healthy diet indicator, recommended food score, and the Mediterranean diet (MeDi). Our review of the literature suggests a generally positive association between healthy diet patterns, AD and AD-related chronic disease risk; however the magnitude of the protective effect is modest in many studies. Consequently, we can only confidently conclude that the MeDi is associated with reduced AD risk, and further studies on the remaining indices need to be carried out. It is our opinion that a combination of dietary scores could predict overall dietary quality and chronic disease risk to a greater extent than one score individually. Analysis in multi-ethnic cohorts, investigating combinations of scores must be completed before firm conclusions can be reached on the ideal combination of scores. Obtaining further insight into the association between dietary patterns, AD and AD-related chronic disease risk may help in prioritizing public health efforts and provide a stronger basis for recommendations to improve dietary patterns

Higher coffee consumption is associated with slower cognitive decline and less cerebral Aβ-amyloid accumulation over 126 months: Data from the Australian imaging, biomarkers, and lifestyle study

Background: Worldwide, coffee is one of the most popular beverages consumed. Several studies have suggested a protective role of coffee, including reduced risk of Alzheimer’s disease (AD). However, there is limited longitudinal data from cohorts of older adults reporting associations of coffee intake with cognitive decline, in distinct domains, and investigating the neuropathological mechanisms underpinning any such associations. Methods: The aim of the current study was to investigate the relationship between self-reported habitual coffee intake, and cognitive decline assessed using a comprehensive neuropsychological battery in 227 cognitively normal older adults from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study, over 126 months. In a subset of individuals, we also investigated the relationship between habitual coffee intake and cerebral Aβ-amyloid accumulation (n = 60) and brain volumes (n = 51) over 126 months. Results: Higher baseline coffee consumption was associated with slower cognitive decline in executive function, attention, and the AIBL Preclinical AD Cognitive Composite (PACC; shown reliably to measure the first signs of cognitive decline in at-risk cognitively normal populations), and lower likelihood of transitioning to mild cognitive impairment or AD status, over 126 months. Higher baseline coffee consumption was also associated with slower Aβ-amyloid accumulation over 126 months, and lower risk of progressing to “moderate,” “high,” or “very high” Aβ-amyloid burden status over the same time-period. There were no associations between coffee intake and atrophy in total gray matter, white matter, or hippocampal volume. Discussion: Our results further support the hypothesis that coffee intake may be a protective factor against AD, with increased coffee consumption potentially reducing cognitive decline by slowing cerebral Aβ-amyloid accumulation, and thus attenuating the associated neurotoxicity from Aβ-amyloid-mediated oxidative stress and inflammatory processes. Further investigation is required to evaluate whether coffee intake could be incorporated as a modifiable lifestyle factor aimed at delaying AD onset

Longitudinal trajectories in cortical thickness and volume atrophy: Superior cognitive performance does not protect against brain atrophy in older adults

Background: Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable. Objective: Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years. Methods: Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed by a discovery phase analyses of additional regions. SCPs were aged 70 + at baseline, scoring at/above normative memory (CVLT-II) levels for demographically similar individuals aged 30–44 years old, and in the unimpaired range for all other cognitive domains over the course of the study. Results: In linear mixed models, following adjustment for multiple comparisons, there were no significant differences between rates of thinning or volume atrophy between SCPs and TOAs in previously identified ROIs, or the discovery phase analyses. With only amyloid-β negative individuals in the analyses, again there were no significant differences between SCPs and TOAs. Conclusion: The increased methodological rigor in classifying groups, together with the influence of cognitive reserve, are discussed as potential factors accounting for our findings as compared to the extant literature on those with superior cognitive performance for their age

The association between Alzheimer\u27s disease-related markers and physical activity in cognitively normal older adults

Previous studies have indicated that physical activity may be beneficial in reducing the risk for Alzheimer\u27s disease (AD), although the underlying mechanisms are not fully understood. The goal of this study was to evaluate the relationship between habitual physical activity levels and brain amyloid deposition and AD-related blood biomarkers (i.e., measured using a novel high-performance mass spectrometry-based assay), in apolipoprotein E (APOE) ε4 carriers and noncarriers. We evaluated 143 cognitively normal older adults, all of whom had brain amyloid deposition assessed using positron emission tomography and had their physical activity levels measured using the International Physical Activity Questionnaire (IPAQ). We observed an inverse correlation between brain amyloidosis and plasma beta-amyloid (Aβ)1−42 but found no association between brain amyloid and plasma Aβ1−40 and amyloid precursor protein (APP)669−711. Additionally, higher levels of physical activity were associated with lower plasma Aβ1−40, Aβ1−42, and APP669−711 levels in APOE ε4 noncarriers. The ratios of Aβ1−40/Aβ1−42 and APP669−711/Aβ1−42, which have been associated with higher brain amyloidosis in previous studies, differed between APOE ε4 carriers and non-carriers. Taken together, these data indicate a complex relationship between physical activity and brain amyloid deposition and potential blood-based AD biomarkers in cognitively normal older adults. In addition, the role of APOE ε4 is still unclear, and more studies are necessary to bring further clarification

Mediterranean diet adherence and rate of cerebral Aβ-amyloid accumulation: Data from the Australian Imaging, Biomarkers and Lifestyle study of ageing

Accumulating research has linked Mediterranean diet (MeDi) adherence with slower cognitive decline and reduced Alzheimer\u27s disease (AD) risk. However, no study to-date has examined the relationship between MeDi adherence and accumulation of cerebral Aβ-amyloid (Aβ; a pathological hallmark of AD) in older adults. Cognitively normal healthy control participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing completed the Cancer Council of Victoria Food Frequency Questionnaire at baseline, which was used to construct a MeDi score for each participant (score range 0-9; higher score indicating higher adherence). Cerebral Aβ load was quantified by Pittsburgh Compound B positron emission tomography at baseline, 18 and 36 months: Only individuals categorised as Aβ accumulators , and thus considered to be on the AD pathway, were included in the analysis (N = 77). The relationship between MeDi adherence, MeDi components, and change in cerebral Aβ load (baseline to 36 months) was evaluated using Generalised Linear Modelling, accounting for age, gender, education, Apolipoprotein E ε4 allele status, body mass index and total energy intake. Higher MeDi score was associated with less Aβ accumulation in our cohort (β = -0.01 ± 0.004, p = 0.0070). Of the individual MeDi score components, a high intake of fruit was associated with less accumulation of Aβ (β = -0.04 ± 0.01, p = 0.00036). Our results suggest MeDi adherence is associated with reduced cerebral AD pathology accumulation over time. When our results are considered collectively with previous data linking the MeDi to slower cognitive decline, it is apparent that MeDi adherence warrants further investigation in the quest to delay AD onset

Plasma amyloid‐beta levels in a pre‐symptomatic dutch‐type hereditary cerebral amyloid angiopathy pedigree: A cross‐sectional and longitudinal investigation

Plasma amyloid‐beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre‐symptomatic Dutch‐type hereditary CAA (D‐CAA) mutation‐carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre‐symptomatic members of a D‐ CAA pedigree were assembled and followed up 3–4 years later (NC = 8;MC = 9). Plasma Aβ1‐40 and Aβ1‐42 were cross‐sectionally and longitudinally analysed at baseline (T1) and follow‐up (T2) and were found to be lower in MCs compared to NCs, cross‐sectionally after adjusting for covari-ates, at both T1(Aβ1‐40: p = 0.001; Aβ1‐42: p = 0.0004) and T2 (Aβ1‐40: p = 0.001; Aβ1‐42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1‐40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma Aβ1‐42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre‐symptomatic CAA, however, further validation studies in larger sample sets are required

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Fifteen years of the Australian imaging, biomarkers and lifestyle (AIBL) study: Progress and observations from 2,359 older adults spanning the spectrum from cognitive normality to Alzheimer\u27s disease

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer\u27s disease dementia (AD)) as an \u27Inception cohort\u27 who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an \u27Enrichment cohort\u27 (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims