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Background Ultra-processed food (UPF) consumption is related to increased morbidity and mortality. However, knowledge on its association with cognitive function is lacking. In this longitudinal study, we examined the associations between UPF intake and cognitive decline in older adults with type-2 diabetes (T2D). Methods The sample included initially nondemented T2D older adults (≥65 years), from the Israel Diabetes and Cognitive Decline study, who had complete information on nutrition at baseline and at least 3 cognitive assessments (mean follow-up 5.3 ± 1.5 years). Nutritional intake was evaluated by a validated Food-Frequency Questionnaire, and foods were categorized as UPF based on NOVA classification. Percent of calories from UPF were calculated from total caloric consumption in total and specific food groups. Mixed effect models were used to examine the link between UPF intake (top vs bottom quartiles) and change in cognitive function overall and in specific domains, adjusting for potential confounders. Results Of the total sample (N = 568; mean age 71.3 ± 4.5 years, 60% men), 141 consumed >31% kcal from UPF (top quartile). Greater intake of ultra-processed meat was associated with a faster decline in executive functions and global cognition (β = −0.041 ± 0.013; p = .002 and β = −0.026 ± 0.010; p = .011, respectively). Additionally, consumption of ultra-processed oils/spreads was associated with faster decline in executive functions and global cognition (β = −0.037 ± 0.014; p = .006 and β = −0.028 ± 0.010; p = .009, respectively). Total UPF consumption and UPF-derived from dairy products and bread/pastries/starch were not associated with cognitive change. Conclusion This study suggests that a high intake of ultra-processed meat and oils/spreads may be associated with accelerated cognitive decline in older individuals with T2D.

Background We examined the cross-sectional and longitudinal relationships of motor functions with depression in older adults with type 2 diabetes (T2D). Methods Participants (n = 984) were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of motor functions (grip strength and gait speed) and of depression (using the 15-item version of the Geriatric Depression Scale [GDS]) approximately every 18 months. We applied Hierarchical Linear Mixed Models (HLMM) to investigate the associations between motor functions and depression adjusting for sociodemographic, cardiovascular factors, overall cognitive score, and subjective report of exhaustion. Results Participants’ baseline characteristics were 72 (±5) years of age (59.6% males), 13 (±4) years of education, Mini-Mental Status Exam (MMSE) score of 28.01 (±1.78), and a GDS score of (2 ± 2.00), consistent with normal cognitive status and lack of major affective symptomatology. Slower gait speed at baseline was associated with higher GDS scores (p = .001) and with their increase over time (p = .049). A decrease in walking speed from baseline was associated with an increase in GDS scores (p = .015). Lower grip strength at baseline was associated with higher GDS scores (p = .002), but not with trajectories in GDS scores over time. A faster decrease in grip strength from baseline was associated with a faster increase in GDS scores (p = .022). Conclusions Both gait speed and grip strength are cross-sectionally associated with depression. However, only gait speed and its decrease over time can potentially be used to predict incident depression symptoms, thus facilitating the introduction of depression prevention strategies.

On behalf of the ISTAART Neuropsychiatric Syndromes Professional Interest Area Psychosis work group, this is a pre-registration for the Phenomenology, Epidemiology, Neurobiology, Prognosis, and Treatment Considerations of Late-Onset Psychosis paper.

Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials This manuscriptwas facilitated by the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART), through the Neuropsychiatric Syndromes professional interest area (PIA). The views and opinions expressed by authors in this publication represent those of the authors and do not necessarily reflect those of the PIA membership, ISTAART or the Alzheimer’s Association. Ganesh M. Babulal receives research support from the BrightFocus Foundation (A2021142S), and NIH/NIA (R01AG074302 AG068183, AG067428, AG056466). Marie-Andr´ee Bruneau has received support from Optimizing Practices, Use, Care and Services - Antipsychotics (OPUS-AP) in Quebec, Canadian Foundation for Healthcare Improvement and Quebec Ministry of Health and Social services. Jennifer Gatchel has received research support from the BrightFocus Foundation, Alzheimer’s Association, and NIH/NIA. Zahinoor Ismail has received support from Brain Canada, Canadian Institutes of Health Research, and Canadian Consortium on Neurodegeneration in Dementia. Sanjeev Kumar has received support from Academic Scholars Award from the Department of Psychiatry, University of Toronto, Brain and Behavior Foundation, National institute on Ageing, BrightFocus Foundation, Brain Canada, Canadian Institute of Health Research, Canadian Consortium on Neurodegeneration in Aging, Centre for Ageing and Brain Health Innovation, Centre for Addiction and Mental Health, University of Toronto. Equipment support from Soterix Medical. Krista L. Lanctˆot has received support from the Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, National Institute on Ageing, Canadian Institutes of Health Research,Weston Brain Institute and the Canadian Consortium on Neurodegeneration in Aging. Moyra E. Mortby has received support from the Australian National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) Dementia Research Development Fellowship #1102028. Nicolas A. Nu˜nez has received support from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM008685. Fabricio Oliveira has received support from FAPESP – The State of S˜ao Paulo Research Foundation (grant #2015/10109-5). Authors’ disclosures available online (https:// www.j-alz.com/manuscript-disclosures/21-5483r2) SI

Physical fitness is an important contributor to healthy aging that improves cognition. Older adults who engage in cardiorespiratory fitness activities show less cognitive decline. To examine whether physical fitness acts as a potential protective mechanism shielding against the negative associations between age and cognition. Specifically, we examined whether physical fitness mediates the relationship between age and processing speed. 114 (M = 63.80, SD = 10.63) senior executives completed a computerized cognitive battery composed of four processing speed tasks. Level of physical fitness was assessed on a treadmill stress test and reported in metabolic equivalents (METs). Older age was associated with slower processing speed (r = 0.25, p = 0.007), whereas greater physical fitness was associated with faster processing speed (r = −0.30, p = 0.001). Path analysis indicated that the association between age and processing speed was fully mediated by the level of physical fitness (Indirect effect: β = 0.10, p = 0.008; Direct effect: β = 0.16, p = 0.20). The findings indicate that physical fitness is a strong mediator of the relationship between age and processing speed and imply that physical fitness makes a major contribution to cognitive reserve during the aging process. The results may suggest that the decrease in physical fitness during aging may partially account for slower cognitive processing.

Backgrounds The efficacy of vitamin E in prevention of diabetes-related complications differs by Haptoglobin (Hp) genotype. Objective To examine the role of Hp genotype in the relationship of vitamin E intake with brain volume in cognitively normal elderly patients with type 2 diabetes. Methods Brain volumes for the superior, middle, and inferior frontal gyri and for the middle temporal gyrus were generated from structural T1 MRI in 181 study participants (Hp 1-1: n = 24, Hp 2-1: n = 77, Hp 2-2: n = 80). Daily vitamin E intake was assessed using the Food Frequency Questionnaire. Analyses of covariance, controlling for demographic and cardiovascular variables was used to evaluate whether the association of daily vitamin E intake with brain volume was modified by Hp genotype. Results Average age was 70.8 (SD = 4.2) with 40% females, and mean Mini-Mental State Examination score of 28.17 (SD = 1.90). A significant interaction was found between vitamin E intake and Hp genotype in inferior frontal gyrus' volume; p = 0.0108. For every 1 microgram increase in vitamin E intake, the volume of the inferior frontal gyrus decreased by 0.955% for Hp 1-1 (p = 0.0348), increased by 0.429% for Hp 2-1 (p = 0.0457), and by 0.077% for Hp 2-2 (p = 0.6318). There were no significant interactions between vitamin E intake and Hp genotype for the middle (p = 0.6011) and superior (p = 0.2025) frontal gyri or for the middle temporal gyrus (p = 0.503). Conclusions The effect of dietary vitamin E on the brain may differ by Hp genotype. Studies examining the impact of vitamin E on brain-related outcomes should consider Hp genotype.

To determine associations of three dietary patterns (Mediterranean (MEDI) diet, the Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean- DASH Intervention for Neurodegenerative Delay (MIND) diet) with cognitive decline in older adults with type 2 diabetes mellitus (T2D).This is a longitudinal observational study. Participants (N = 960) from the Israel Diabetes and Cognitive Decline (IDCD) study were included in this study. A multivariable-adjusted model including all three dietary patterns concurrently was developed to investigate their independent effect on cognitive decline.The mean follow up was 4.1 ± 2.1 years. While high adherence to both the MIND and the MEDI diet was associated with a slower decline, in the multivariable model only the associations of higher MEDI diet intake with greater decline in global cognition and in executive functions remained significant (β = 0.013, SE = 0.006; P = 0.042; β = 0.001, SE = 0.008, Pv = 0.023 respectively).In older adults with T2D, adherence to the MEDI is related to better cognitive trajectory. Diet is a meaningful factor in the path linking T2D and cognition.

We compared retinal layers' thickness between apolipoprotein E (Participants (N = 245) underwent spectral domain optical coherence tomography. Multivariate analyses of covariance adjusting for age, sex, education, and best corrected vision acuity was used to compare retinal thickness betweenParticipants' mean age was 59.60 (standard deviation = 6.42) with 66.4% women and 32.2%A thicker macula is observed already in midlife asymptomatic

Aim: We investigated the relationship between midlife C-reactive protein (CRP) levels in men with coronary heart disease (CHD) and depressive symptoms at old age. CRP levels were measured in a subs...

Background To evaluate the effects of adaptive and tailored computerized cognitive training on cognition and disease self-management in older adults with diabetes. Methods This was a single-blind trial. Eighty-four community-dwelling older adults with diabetes were randomized into a tailored and adaptive computerized cognitive training or a generic, non-tailored or adaptive computerized cognitive training condition. Both groups trained for 8 weeks on the commercially available CogniFit program and were supported by a range of behavior change techniques. Participants in each condition were further randomized into a global or cognition-specific self-efficacy intervention, or to a no self-efficacy condition. The primary outcome was global cognition immediately following the intervention. Secondary outcomes included diabetes self-management, meta-memory, mood, and self-efficacy. Assessments were conducted at baseline, immediately after the training, and at a 6-month follow-up. Results Adherence and retention were lower in the generic computerized cognitive training condition, but the self-efficacy intervention was not associated with adherence. Moderate improvements in performance on a global cognitive composite at the posttreatment assessments were observed in both cognitive training conditions, with further small improvement observed at the 6-month follow-up. Results for diabetes self-management showed a modest improvement on self-rated diabetes care for both intervention conditions following the treatment, which was maintained at the 6-month follow-up. Conclusions Our findings suggest that older adults at higher dementia risk due to diabetes can show improvements in both cognition and disease self-management following home-based multidomain computerized cognitive training. These findings also suggest that adaptive difficulty and individual task tailoring may not be critical components of such interventions. Trial registration NCT02709629.

Background Objective and subjective health are two powerful constructs which predict morbidity and mortality across a range of conditions including Type 2 Diabetes (T2D). Studies, however, suggest that these two constructs do not necessarily correlate, as some people with poor objective health perceive their health as good, while other people with good objective health perceive their health as poor. We seek to examine the role of personality as a moderator of the associations between objective and subjective health among older adults with T2D, who are likely to experience poor objective and subjective health due to their chronic medical condition. Methods Cross-sectional study of 368 individuals with T2D (72 ± 4 years, 42% women), participating in the Israel Diabetes and Cognitive Decline Study. Personality was conceptualized using the five-factor model (agreeableness, conscientiousness, extraversion, neuroticism, openness). Objective health was operationalized by T2D-related clinical status, cognitive function, and motor ability. Subjective health was assessed using a single self-report question. Hayes' process macro was used for the moderation analyses. Results The objective-subjective health associations were stronger among individuals with increased neuroticism (proportion of days covered: p = 0.02; cognitive function: p = 0.003; hand grip: p = 0.02; 3-m walk: p = 0.04) as well as decreased openness (cognitive status: p = 0.04) and agreeableness (3-m walk: p = 0.02). Discussion Personality traits, and specifically neuroticism, can modify the associations between objective and subjective health in older adults with T2D. Findings contribute to the understanding of health as a multidimensional construct that encompasses medical and psychological aspects, especially among older adults with a chronic illness.

Objectives The APOE-e4 genotype has been associated with old-age depression, but this relationship has been rarely investigated in type 2 diabetes (T2D) older adults, who are at significantly increased risk for depression, a major contributor to T2D complications. We examined whether trajectories of depression symptoms over time differ by APOE-e4 genotype in older adults with T2D. Methods Participants [n=754 (13.1% APOE-e4 carriers)] were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of depression approximately every 18 months using the 15-item version of the Geriatric Depression Scale (GDS) and the depression subscale of the Neuropsychiatric Inventory (NPI). APOE was defined as a dichotomy of e4 carriers and non-carriers. We used Hierarchical Linear Mixed Models (HLMM) that modeled the effects of APOE status on repeated GDS and NPI-depression scores in an unadjusted model (Model 1), adjusting for demographic factors (Model 2) and additionally adjusting for cardiovascular factors and global cognition (Model 3). Results Participants' mean age was 71.37 (SD=4.5); 38.2% female. In comparison to non-carriers, APOE-e4 carriers had lower mean GDS scores (β=-0.46, p=0.018) and lower NPI-depression scores (β=-0.170, p=0.038) throughout all study follow period. The groups did not differ in the slope of change over time in GDS (β=-0.005, p=0.252) or NPI-depression (β=-0.001, p=0.994) scores. Additional adjustment for cardiovascular factors and global cognition did not alter these results. Conclusions In older adults with T2D, APOE-e4 carriers have less depressive symptoms in successive measurements suggesting they may be less susceptible to depression. This article is protected by copyright. All rights reserved.

OBJECTIVE Depression is highly frequent in older adults with type 2 diabetes and is associated with cognitive impairment, yet little is known about how various depression dimensions differentially affect cognition. We investigated longitudinal associations of specific depression dimensions with cognitive decline. RESEARCH DESIGN AND METHODS Participants (N = 1,002) were from the Israel Diabetes and Cognitive Decline study, were ≥65 years of age, had type 2 diabetes, and were not experiencing dementia at baseline. Participants underwent a comprehensive neuropsychological battery at baseline and every 18 months thereafter, including domains of episodic memory, attention/working memory, semantic categorization/language, and executive function, and Z-scores of each domain were averaged and further normalized to calculate global cognition. Depression items from the 15-item Geriatric Depression Scale were measured at each visit and subcategorized into five dimensions: dysphoric mood, withdrawal-apathy-vigor (entitled apathy), anxiety, hopelessness, and memory complaint. Random coefficients models examined the association of depression dimensions with baseline and longitudinal cognitive functioning, adjusting for sociodemographics and baseline characteristics, including cardiovascular risk factors, physical activity, and use of diabetes medications. RESULTS In the fully adjusted model at baseline, all dimensions of depression, except for anxiety, were associated with some aspect of cognition (P values from 0.01 to 0.01). CONCLUSIONS Apathy was associated with a faster cognitive decline in executive function. These findings highlight the heterogeneity of depression as a clinical construct rather than as a single entity and point to apathy as a specific risk factor for cognitive decline among older adults with type 2 diabetes.

Background: Family history of Alzheimer’s disease (AD) is associated with increased dementia-risk. Objective: The Israel Registry for Alzheimer’s Prevention (IRAP) is a prospective longitudinal study of asymptomatic middle-aged offspring of AD patients (family history positive; FH+) and controls (whose parents have aged without dementia; FH–) aimed to unravel the contribution of midlife factors to future cognitive decline and dementia. Here we present the study design, methods, and baseline characteristics. Methods: Participants are members of the Maccabi Health Services, 40–65 years of age, with exquisitely detailed laboratory, medical diagnoses and medication data available in the Maccabi electronic medical records since 1998. Data collected through IRAP include genetic, sociodemographic, cognitive, brain imaging, lifestyle, and health-related characteristics at baseline and every three years thereafter. Results: Currently IRAP has 483 participants [mean age 54.95 (SD = 6.68) and 64.8% (n = 313) women], 379 (78.5%) FH+, and 104 (21.5%) FH–. Compared to FH–, FH+ participants were younger (p = 0.011), more often males (p = 0.003) and with a higher prevalence of the APOE E4 allele carriers (32.9% FH+, 22% FH–; p = 0.040). Adjusting for age, sex, and education, FH+ performed worse than FH–in global cognition (p = 0.027) and episodic memory (p = 0.022). Conclusion: Lower cognitive scores and higher rates of the APOE E4 allele carriers among the FH+ group suggest that FH ascertainment is good. The combination of long-term historical health-related data available through Maccabi with the multifactorial information collected through IRAP will potentially enable development of dementia-prevention strategies already in midlife, a critical period in terms of risk factor exposure and initiation of AD-neuropathology.