-->PONE-D-25-65508-->-->Loneliness and Cognitive Decline Among U.S. Adults: A Stratified Analysis of the BRFSS-->-->PLOS One

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Reviewers' comments:

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Reviewer #1: Partly

Reviewer #2: Yes

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-->2. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: I Don't Know

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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-->5. Review Comments to the Author

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Reviewer #1: Thank you for the opportunity to read this interesting and important paper that investigated the relationship between the frequency of loneliness and subjective cognitive decline. The authors found that the frequency of loneliness was associated with subjective cognitive decline, showing predicted probability of SCD of 9.9% in respondents that never felt lonely, all the way up to 45% in those that always felt lonely. The paper is well written, clearly communicates study methods, and adds valuable insights into the broader literature on impacts and significance of social disconnection and demonstrates a thoughtful analysis to support whether interventions could be worthwhile. There are a few comments that the authors could address to strengthen the piece.

Major comments:

1.) The language used in certain parts of the paper needs adjustment.

- The study conclusions, "These findings identify loneliness as a modifiable social determinant of cognitive health" could be more cautiously and grounded in study findings

- The claim that a one-time cross-sectional assessment of loneliness describes chronicity of loneliness is a big claim, I believe the authors are limited since BRFSS doesn't include longitudinal data that would be more appropriate to look at trends for individuals rather than 1 time assessment of "chronicity". The primary difference between frequency and chronicity is in their focus: frequency measures how often an event occurs within a specific period, while chronicity measures how long a condition persists over a long-term, sustained period, there is a slight difference given what data is available and the wording should reflect this.

-There are several instances through the manuscript that outcome of "cognitive decline" is referred to without listing "subjective", it is important to include subjective throughout to minimize confusion, consider including in title and tables as well as text.

2.) Respondents that were excluded from the analyses because of "don't know, refused or missing key variable"- team may want to describe who is missing from their analysis. It is also possible that individuals with greatest loneliness frequency do not make it into a study like BRFSS and this limitation could be acknowledged.

3.) The authors clearly communicate study methods and it makes sense the use of adjusted marginal probabilities, but unclear if best way to assess dose response would be pairwise comparisons rather than trend test, and if pairwise is used then would consider the need for multiple pairwise comparisons correction to control the likelihood of false positives.

4.) The authors appropriately completed sensitivity analyses, but do not state which auxillary variables were included in their imputation models and this should be clarified as well as justification that missing at random assumption was met.

5.) One area that requires more consideration and explanation, Table 1 presents total population 86K and proportion across loneliness categories, only 2.4% of population always lonely and only 2.71% usually lonely (while Never lonely is ~45% and sometimes ~21%, and rarely ~30%). Given small proportion of individuals in these categories there is concern when using these group to calculate average marginal effects that there could be significant errors in estimation due to high variance and small sample size bias. While the marginal effects themselves might not be biased, the precision of these estimates (the standard errors) is often severely compromised, leading to unreliable inferences.

6.) The authors previous paper explores associations between loneliness and mental health (Akinyemi O, Abdulrazaq W, Fasokun M, Ogunyankin F, Ikugbayigbe S, Nwosu U, Michael M, Hughes K, Ogundare T. The impact of loneliness on depression, mental health, and physical well-being. PLoS One. 2025 Jul 9;20(7):e0319311. doi: 10.1371/journal.pone.0319311. PMID: 40632698; PMCID: PMC12240311.), which is likely relevant to subjective cognitive decline, but this is not examined in these analyses, unclear why. The paper states that they" lacked information on potentially confounding factors such as depressive symptoms", although the BRFSS has these measures, this needs to be clarified.

A few additional minor comments:

1.) In the methods section of abstract age range listed is "16-66" but minimum age of those in study was 18, this should be clarified or fixed.

2.) Limitation of cross sectional studies listed in introduction seems erroneous as the current study is also cross sectional, authors may want to be reword/ get more specific that other studies have looked at loneliness as binary yes/no without considering frequency/dose which is what it seems they are trying to convey

3.) The BRFSS study question on how often participants feel lonely does not include a timeframe, like over the past X amount of time, so it's unclear how participants may interpret this question, while question regarding SCD has clear time delineation of 12 months. Most other BRFSS study questions consider 30 day timeframe so its possible that is assumed by the participants, this could be conveyed more clearly for readers that are not familiar with BRFSS

4.) Methods section shares covariates were selected 'based on prior research', authors should include reference for what is being referred to.

5.) Some additional more recent references to consider that could be used to situate this current study in the discussion include:

- Kang JE, Martire LM, Graham-Engeland JE, Almeida DE, Sliwinski MJ. Chronic loneliness and longitudinal changes in cognitive functioning. BMC Public Health. 2025 Mar 29;25(1):1190. doi: 10.1186/s12889-025-22313-2. PMID: 40155901; PMCID: PMC11954266.

- Luchetti M, Aschwanden D, Stephan Y, Karakose S, Milad E, Miller AA, Zavala D, Hajek A, Terracciano A, Sutin AR. Loneliness and subjective cognitive concerns in daily life. Aging Ment Health. 2025 Oct;29(10):1856-1864. doi: 10.1080/13607863.2025.2519672. Epub 2025 Jun 20. PMID: 40539421; PMCID: PMC12321047.

- Ren Z, Luo Y, Liu Y, Gao J, Liu J, Zheng X. Prolonged loneliness and risk of incident cognitive decline and dementia: A two-cohort study. J Affect Disord. 2025 Jun 1;378:254-262. doi: 10.1016/j.jad.2025.03.001. Epub 2025 Mar 5. PMID: 40044082.

Reviewer #2: Thank you for the opportunity to review this manuscript.

Introduction

The Introduction would benefit from revisions to improve clarity, logical flow, and conceptual grounding across paragraphs. Here are some minor and major points:

1. Sentence structure and flow (Lines 57–58):

The sentence “Defined as a distressing subjective state arising when perceived social connections are inadequate” is a fragment and should be rewritten as a complete sentence or integrated with the preceding sentence.

2. Conceptual clarity between loneliness and social isolation (Lines 59–62):

The Introduction moves abruptly from prevalence estimates of social isolation (e.g., “nearly one quarter of those aged 65 and older are socially isolated”) to stating that loneliness and social isolation are distinct, followed immediately by “the present study focuses on loneliness.” This transition should be smoother.

3. Psychosocial vs. physiological framing (Lines 63–65):

The phrase “Beyond its psychosocial toll” implies that psychosocial consequences of loneliness have already been discussed, but they are not described earlier in the paragraph. This contrast should be clarified or rephrased to maintain logical continuity.

4. Insufficient contextualization of subjective cognitive decline (Lines 69–70):

Subjective cognitive decline is introduced briefly via prevalence estimates but is not conceptually developed. Given that cognitive decline, dementia, and SCD are related but distinct constructs, the authors should provide additional background on what SCD indicates, what it predicts, and why it is important to study SCD separately—particularly in relation to loneliness.

5. Blurring of background and methods (Lines 85–87):

The description of the BRFSS SCD item reads as methodological detail and may be more appropriate for the Methods section, or should be reframed as background information motivating the study.

6. Limited justification for analytic “contributions” (Lines 88–94):

The stated contributions would benefit from clearer theoretical or empirical justification, including: why a dose–response relationship between loneliness and SCD is hypothesized, how causal language is justified given the cross-sectional design, and why associations are expected to differ by sex, age, and race/ethnicity.

7. Need for more specific hypotheses (Lines 96–98):

The hypotheses are broad and largely restate the analytic plan. More specific, theory-driven hypotheses would strengthen the Introduction and better align with the proposed contributions.

Methods

1. Clearer justification for the inclusion of several covariates:

In particular, variables such as health insurance type, metropolitan status, urbanicity, and language appear to be included without explanation beyond their availability in the dataset. The authors should clarify the conceptual or empirical rationale for adjusting for these factors (e.g., whether they are considered confounders, proxies for access to care or socioeconomic context, or related to reporting of loneliness or subjective cognitive decline). Providing this justification would help readers assess the appropriateness of the adjustment set and improve interpretability of the findings.

Also, depressive symptoms/depression is a well-known factor of loneliness and cognition. Please include it as covariate.

2. Age categorization (18–64 vs. ≥65) should be justified, as this choice may obscure heterogeneity within older age groups.

Results/Discussion

1. Use of “chronic loneliness” or “persistent loneliness” with cross-sectional measurement:

The Results section refers to “chronic loneliness or persistent loneliness,” but loneliness appears to be measured at a single time point without information on duration or persistence. Without longitudinal or retrospective data on how long loneliness has been experienced, it is unclear how chronicity is being operationalized. The authors should clarify what they mean by “chronic” in this context or revise the terminology to avoid implying temporal persistence that is not measured.

2. Ambiguous terminology (e.g., “frequently married”):

The phrase “frequently married” is unclear and potentially misleading.

3. Overinterpretation of baseline group differences in a very large sample:

The statement that baseline characteristics “highlight pronounced socioeconomic, psychosocial, and demographic differences” may overstate the substantive meaning of these differences. Given the very large sample size, statistically significant differences are expected even when effect sizes are small. The authors should be cautious in interpreting these differences and consider reporting or referencing effect sizes, or rephrasing to avoid implying meaningful group separation based solely on statistical significance.

4. Dose-Response Interpretation:

While the graded pattern across loneliness categories is visually compelling, the interpretation of a strong “dose–response relationship” warrants additional verification. Given the very large sample size, statistically significant differences across all categories may reflect high power rather than substantively meaningful contrasts. I encourage the authors to supplement pairwise comparisons with additional robustness checks, such as reporting effect sizes (e.g., absolute risk differences), conducting a formal test for trend, or evaluating potential non-linear or threshold effects (e.g., contrasting high-frequency loneliness vs. lower-frequency groups). This would strengthen confidence that the observed pattern reflects a meaningful dose–response relationship rather than precision alone.

Also, the dose–response framing implicitly assumes a monotonic relationship in which increasing frequency of loneliness is uniformly more harmful. However, prior loneliness research suggests that occasional or moderate loneliness may be normative and not necessarily detrimental, whereas adverse effects may emerge only beyond certain thresholds of frequency or severity. The authors may wish to consider alternative characterizations of the pattern (e.g., threshold or non-linear effects) or to discuss why a linear or monotonic interpretation is theoretically justified in this context.

Clarifying these issues would strengthen the interpretation of the findings and avoid overstatement of dose–response effects based solely on categorical contrasts in a cross-sectional, high-powered dataset.

5. Causal and temporal language not supported by the data:

Phrases such as “detrimental impact,” “consequences,” and “heightened vulnerability” imply a causal or longitudinal interpretation. Given the cross-sectional design and single-time measurement of loneliness and subjective cognitive decline, the authors should avoid language suggesting effects or consequences and instead describe these findings as differences in associations or predicted probabilities.

6. Outcome Interpretation and Terminology:

The results and discussion section incorrectly refers to the outcome as “predicted cognitive function”. However, the outcome is subjective cognitive decline, operationalized as a binary self-report of worsening confusion or memory over the past 12 months. This measure does not capture cognitive function or performance per se, but rather perceived cognitive change. Even though SCD has been associated with objective cognitive impairment and dementia risk in prior studies, describing results as differences in “cognitive function” overstates what is measured. The authors should revise the language throughout to refer to predicted probability of subjective cognitive decline or self-reported cognitive difficulties, rather than cognitive function.

7. Interpretation of Sex Differences in High Loneliness:

The explanation offered for the observed sex difference among individuals reporting persistent loneliness is not well aligned with the results or the constructs measured in this study. While the authors report that women who are always lonely have higher predicted probabilities of subjective cognitive decline than men, the proposed explanation—that women’s family and social networks have weakened—invokes objective social network characteristics that were neither measured nor analyzed. This is particularly problematic given the authors’ earlier emphasis that loneliness and social isolation are related but distinct constructs.

As currently written, this explanation appears speculative and not directly supported by the data. The authors should either provide empirical evidence linking sex differences in loneliness-related cognitive complaints to network disruption, or reframe this interpretation more cautiously (e.g., in terms of differential psychological, emotional, or perceptual responses to loneliness among women). Clarifying this distinction would improve conceptual consistency and strengthen the discussion.

8. Racial/Ethnic Differences and Cultural Interpretation:

The discussion of racial/ethnic differences raises an important point about potential cultural variation in how loneliness relates to cognition, but this section would benefit from further development. Statements referring to “stronger family and community networks,” “culturally distinct interpretations of loneliness,” and “differences in reporting SCD” are plausible but remain speculative and are not sufficiently elaborated.

Given that the authors invoke “complex cultural differences” to interpret these findings, it would strengthen the discussion to expand on what these differences may entail, drawing more explicitly on prior literature (e.g., cultural norms around emotional expression, familism, stigma, or differential meaning of loneliness and cognitive complaints across racial/ethnic groups).

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Reviewer #1: No

Reviewer #2: No

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Loneliness and Cognitive Decline Among U.S. Adults: A Stratified Analysis of the BRFSS

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Dear Dr. Fasokun,

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Dear Authors,

I am pleased to inform you that, following the completion of the review process, your manuscript entitled “Loneliness and Cognitive Decline Among U.S. Adults: A Stratified Analysis of the BRFSS” has been accepted for publication in PLOS One.

Your revisions have satisfactorily addressed the comments raised during the review process.

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Reviewers' comments:

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-->Comments to the Author

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Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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-->2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. -->

Reviewer #1: Yes

Reviewer #2: Yes

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-->3. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: I Don't Know

Reviewer #2: Yes

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-->4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.-->

Reviewer #1: Yes

Reviewer #2: Yes

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-->5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.-->

Reviewer #1: Yes

Reviewer #2: Yes

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-->6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)-->

Reviewer #1: The authors were fully responsive to suggested edits which have strengthened the paper.

No additional recommendations

Reviewer #2: (No Response)

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Reviewer #2: No

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