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. 2022 Sep 6:53:101643.
doi: 10.1016/j.eclinm.2022.101643. eCollection 2022 Nov.

Different loneliness types, cognitive function, and brain structure in midlife: Findings from the Framingham Heart Study

Affiliations

Different loneliness types, cognitive function, and brain structure in midlife: Findings from the Framingham Heart Study

Qiushan Tao et al. EClinicalMedicine. .

Abstract

Background: It remains unclear whether persistent loneliness is related to brain structures that are associated with cognitive decline and development of Alzheimer's disease (AD). This study aimed to investigate the relationships between different loneliness types, cognitive functioning, and regional brain volumes.

Methods: Loneliness was measured longitudinally, using the item from the Center for Epidemiologic Studies Depression Scale in the Framingham Heart Study, Generation 3, with participants' average age of 46·3 ± 8·6 years. Robust regression models tested the association between different loneliness types with longitudinal neuropsychological performance (n = 2,609) and regional magnetic resonance imaging brain data (n = 1,829) (2002-2019). Results were stratified for sex, depression, and Apolipoprotein E4 (ApoE4).

Findings: Persistent loneliness, but not transient loneliness, was strongly associated with cognitive decline, especially memory and executive function. Persistent loneliness was negatively associated with temporal lobe volume (β = -0.18, 95%CI [-0.32, -0.04], P = 0·01). Among women, persistent loneliness was associated with smaller frontal lobe (β = -0.19, 95%CI [-0.38, -0.01], P = 0·04), temporal lobe (β = -0.20, 95%CI [-0.37, -0.03], P = 0·02), and hippocampus volumes (β = -0.23, 95%CI [-0.40, -0.06], P = 0·007), and larger lateral ventricle volume (β = 0.15, 95%CI [0.02, 0.28], P = 0·03). The higher cumulative loneliness scores across three exams, the smaller parietal, temporal, and hippocampus volumes and larger lateral ventricle were evident, especially in the presence of ApoE4.

Interpretation: Persistent loneliness in midlife was associated with atrophy in brain regions responsible for memory and executive dysfunction. Interventions to reduce the chronicity of loneliness may mitigate the risk of age-related cognitive decline and AD.

Funding: US National Institute on Aging.

Keywords: Alzheimer's disease; Brain health; Cohort study; Dementia; Neuroimaging; Social isolation.

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Conflict of interest statement

All authors claim no financial relationships with commercial interests.

Figures

Figure 1
Figure 1
Flow-chart of the study sample. Age is reported in years with [95%CI] for each exam and subset. CERAD-WL and VST were longitudinally mearsured from 2008 to 2019. Other cognitive tests include Logical Memory, Visual Reproduction, Trails A and Trails B, and the Boston Naming Test. FHS Gen 3= Framingham Heart Study Generation 3. CES-D = Center for Epidemiologic Studies Depression Scale. CERAD-WL = CERAD Word List Memory Test. VST = Victoria Stroop Test. AD8 = Washington University Dementia Screening Test. MoCA = Montreal Cognitive Assessment.
Figure 2
Figure 2
The dose-response relationship between cumulative loneliness and brain volumes. The loneliness scores across three exams were added to get a cumulative score for loneliness for each participant. A higher score indicates higher chronicity of loneliness over three exams. Robust linear regression models were used to study the relationship between cumulative loneliness scores and brain volumes as outcomes. The outcomes were the z-scores of MRI brain volumes adjusted for head size (y-axis); the predictors were the longitudinal cumulative loneliness scores (CLS) across three exams. Specifically, the labels (1 to 7) of the x-axis were doses of loneliness frequency, which were defined as the sum score of the 4-point Likert scale (0-3) across three exams. Panel (I) shows all subjects, whereas in Panel (II), the sample was stratified by ApoE4 carrier status. All models were adjusted for baseline age, sex, education, and the time difference between the dates of the last loneliness exam (exam 3) and the MRI scans. Statistical significance was indicated as *p < 0.05, **p < 0.01, ***p < 0.001

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