INTRODUCTION: We investigated the longitudinal relationship between cortical amyloid deposition, anxiety, and depression and the risk of incident mild cognitive impairment (MCI). METHODS: We followed 1440 community-dwelling, cognitively unimpaired individuals aged ≥ 50 years for a median of 5.5 years. Clinical anxiety and depression were assessed using Beck Anxiety and Depression Inventories (BAI, BDI-II). Cortical amyloid beta (Aβ) was measured by Pittsburgh compound B positron emission tomography (PiB-PET) and elevated deposition (PiB+) was defined as standardized uptake value ratio ≥ 1.48. We calculated Cox proportional hazards models with age as the time scale, adjusted for sex, education, and medical comorbidity. RESULTS: Cortical Aβ deposition (PiB+) independent of anxiety (BAI ≥ 10) or depression (BDI-II ≥ 13) increased the risk of MCI. There was a significant additive interaction between PiB+ and anxiety (joint effect hazard ratio 6.77; 95% confidence interval 3.58-12.79; P = .031) that is, being PiB+ and having anxiety further amplified the risk of MCI. DISCUSSION: Anxiety modified the association between PiB+ and incident MCI.

• Keywords
• Pittsburgh compound B positron emission tomography, amyloid imaging, anxiety, depression, mild cognitive impairment,
• MeSH
• Alzheimer Disease * psychology   MeSH
• Amyloid beta-Peptides metabolism   MeSH
• Aniline Compounds MeSH
• Depression epidemiology   psychology   MeSH
• Cognitive Dysfunction * diagnostic imaging   epidemiology   psychology   MeSH
• Humans MeSH
• Brain metabolism   MeSH
• Neuropsychological Tests MeSH
• Positron-Emission Tomography methods   MeSH
• Anxiety epidemiology   psychology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Amyloid beta-Peptides MeSH
• Aniline Compounds MeSH

We here posit that measurements of midlife cognition can be instructive in understanding cognitive disorders. Even though molecular events signal possible onset of cognitive disorders decades prior to their clinical diagnoses, cognition and its possible early changes in midlife remain poorly understood. We characterize midlife cognition in a cognitively healthy population-based sample using the Cogstate Brief Battery and test for associations with cardiovascular, adiposity-related, lifestyle-associated, and psychosocial variables. Learning and working memory showed significant variability and vulnerability to psychosocial influences in midlife. Furthermore, midlife aging significantly and progressively increased prevalence of suboptimal cognitive performance. Our findings suggest that physiological changes in cognition, measured with simple tests suitable for use in everyday clinical setting, may signal already in midlife the first clinical manifestations of the presymptomatic biologically defined cognitive disorders. This pilot study calls for longitudinal studies investigating midlife cognition to identify clinical correlates of biologically defined cognitive disorders.

• Keywords
• cognitive disorders, cognitive performance, midlife cognition, psychosocial variables, quality of life, suboptimal cognition,
• Publication type
• Journal Article MeSH

OBJECTIVE: The purpose of this study was to test the hypothesis that subcortical β-amyloid (Aβ) deposition was associated with elevated scores on standardized measures of depressive and anxiety symptoms when compared with cortical (Aβ) deposition in persons without dementia. METHODS: The authors performed a cross-sectional study, derived from the population-based Mayo Clinic Study of Aging, comprising participants aged ≥70 years (N=1,022; 55% males; 28% apolipoprotein E [APOE] ε4 carriers; without cognitive impairment, N=842; mild cognitive impairment; N=180). To assess Aβ deposition in cortical and subcortical (the amygdala, striatum, and thalamus) regions, participants underwent Pittsburgh Compound B positron emission tomography (PiB-PET) and completed the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). The investigators ran linear regression models to examine the association between PiB-PET standardized uptake value ratios (SUVRs) in the neocortex and subcortical regions and depressive and anxiety symptoms (BDI-II and BAI total scores). Models were adjusted for age, sex, education level, and APOE ε4 carrier status and stratified by cognitive status (without cognitive impairment, mild cognitive impairment). RESULTS: Cortical PiB-PET SUVRs were associated with depressive symptoms (β=0.57 [SE=0.13], p<0.001) and anxiety symptoms (β=0.34 [SE=0.13], p=0.011). PiB-PET SUVRs in the amygdala were associated only with depressive symptoms (β=0.80 [SE=0.26], p=0.002). PiB-PET SUVRs in the striatum and thalamus were associated with depressive symptoms (striatum: β=0.69 [SE=0.18], p<0.001; thalamus: β=0.61 [SE=0.24], p=0.011) and anxiety symptoms (striatum: β=0.56 [SE=0.18], p=0.002; thalamus: β=0.65 [SE=0.24], p=0.008). In the mild cognitive impairment subsample, Aβ deposition, regardless of neuroanatomic location, was associated with depressive symptoms but not anxiety symptoms. CONCLUSIONS: Elevated amyloid deposition in cortical and subcortical brain regions was associated with higher depressive and anxiety symptoms, although these findings did not significantly differ by cortical versus subcortical Aβ deposition. This cross-sectional observation needs to be confirmed by a longitudinal study.

• Keywords
• Amyloid Deposition, Anxiety, Depression,
• MeSH
• Amyloid beta-Peptides metabolism   MeSH
• Apolipoprotein E4 MeSH
• Depression psychology   MeSH
• Cognitive Dysfunction metabolism   MeSH
• Brief Psychiatric Rating Scale MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Brain diagnostic imaging   metabolism   MeSH
• Positron-Emission Tomography MeSH
• Cross-Sectional Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Anxiety psychology   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amyloid beta-Peptides MeSH
• Apolipoprotein E4 MeSH