Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: A replication study from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD) project.

OBJECTIVES: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset. DESIGN/METHODS: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). RESULTS: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. CONCLUSIONS: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.

Functioning in older adults with bipolar disorder: A report on recommendations by the International Society of bipolar disorder (ISBD) older adults with bipolar disorder (OABD) task force.

OBJECTIVES: Despite the importance of psychosocial functioning impairment in Bipolar Disorder (BD), its role among Older Adults with BD (OABD) is not well known. The development of guidelines for the assessment of psychosocial functioning helps to facilitate a better understanding of OABD and can lead to better tailored interventions to improve the clinical outcomes of this population. METHODS: Through a series of virtual meetings, experts from eight countries in the International Society of Bipolar Disorder (ISBD) on OABD task force developed recommendations for the assessment of psychosocial functioning. RESULTS: We present (1) a conceptualization of functioning in OABD and differences compared with younger patients; (2) factors related to functioning in OABD; (3) current measures of functioning in OABD and their strengths and limitations; and, (4) other potential sources of information to assess functioning. CONCLUSIONS: The task force created recommendations for assessing functioning in OABD. Current instruments are limited, so measures specifically designed for OABD, such as the validated FAST-O scale, should be more widely adopted. Following the proposed recommendations for assessment can improve research and clinical care in OABD and potentially lead to better treatment outcomes.

Factors associated with brain volume in major depression in older adults without dementia: results from a large autopsy study.

OBJECTIVE: We examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables. METHODS: In this study, 1373 participants (787 male) aged 50 years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull. RESULTS: Mean age at death was 68.6 ± 11.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p < 0.001), lower education (years; p < 0.001), hypertension (p = 0.001), diabetes (p = 0.006), and female gender (p < 0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (ß = -0.86, 95% CI = -26.50 to 24.77, p = 0.95). CONCLUSIONS: In this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education. Copyright © 2017 John Wiley & Sons, Ltd.

Neuropathology of depression in non-demented older adults: A large postmortem study of 741 individuals.

Associations between age-related neuropathological lesions and adult-onset lifetime major depressive disorder (a-MDD), late-life MDD (LLD), or depressive symptoms close to death (DS) were examined in a large community sample of non-demented older adults. Seven hundred forty-one individuals (age at death = 72.2 ± 11.7 years) from the Biobank for Aging Studies were analyzed. a-MDD was present in 54 (7.3%) participants, LLD in 80 (10.8%), and DS in 168 (22.7%). After adjustment for covariates and compared to controls, a-MDD, LDD and DS were associated with small vessel disease (p = 0.039, p = 0.003, and p = 0.003 respectively); LLD, and DS were associated with brain infarcts (p = 0.012, p = 0.018, respectively) and Lewy body disease (p = 0.043, p = 0.002, respectively). DS was associated with beta-amyloid plaque burden (p = 0.027) and cerebral amyloid angiopathy (p = 0.035) in cognitively normal individuals (Clinical Dementia Rating scale = 0). Vascular brain pathology was the strongest correlate of clinical depictions of depression in the absence of dementia, corroborating the vascular hypothesis of depression. Lewy body pathology underlay DS. An older adult with DS or LLD should be monitored for possible cognitive decline or neurodegenerative disorders.

Mental Health of Medical Students Before and During COVID-19 Pandemic: a 3-Year Prospective Study.

Background: Very few studies prospectively analyzed medical students' mental health before and during the COVID-19 pandemic. This study aimed to prospectively evaluate mental health in medical students in 2018, 2019, and 2020 during the COVID-19 pandemic lockdown. Methods: All students from first to fourth year were invited to participate in 2018. These students were also invited to participate in the same period in 2019 and 2020 (during the peak of the COVID-19 lockdown). The Self-Reporting Questionnaire (SRQ-20), created by the WHO to investigate 20 nonpsychotic psychiatric symptoms, was used to evaluate common mental disorders. The cut-off for relevant symptom severity for mental distress is seven (SRQ-20 ≥ 7). Results: In the years 2018, 2019, and 2020, a total of 860 SRQ-20 questionnaires were completed. Overall, mean SRQ-20 scores were 8.2 ± 4.6, and SRQ-20 ≥ 7 frequency was 60.5%. When comparing the years 2018, 2019, and 2020, no differences were found for either SRQ-20 scores (8.4 ± 4.7, 8.2 ± 4.6, and 7.8 ± 4.4, respectively; p = 0.351) or SRQ-20 ≥ 7 frequency (62.2%, 60.9%, and 59.2%, respectively; p = 0.762). Conclusion: In contrast to our initial hypothesis, stable results on mental health measures were found even during the 2020 COVID-19 lockdown. Maintenance of daily routines through distance learning and the continuation of adapted clerkship activities with strict safety measures could have contributed to these results. However, this study points to high overall levels of common mental disorders, especially among women. Further studies should be conducted to understand all the factors responsible for such stability, such as social and economic support, resilience, or even previous high levels of common mental disorders.

Problematic Social Media Use and Its Relationship with Depression or Anxiety: A Systematic Review.

There has been a notable increase in social media and Internet use over recent decades, not only for social interaction or entertainment, but also for working and meeting tools, as seen during the COVID-19 pandemic. A relationship between this usage and the development of mental illness is frequently hypothesized, but a few studies have empirical findings. This study is a systematic review of the relationship between social media use and depression or anxiety. Our Medline search yielded 1,747 papers. Our study found a strong and often bidirectional relationship between social media use and depression or anxiety. This relationship was frequently related to problematic social media use. No definite linear relationship was found between time spent using social media and depressive or anxious symptoms, but usually, the longer the time spent in that activity, the worse the outcomes. Factors related to problematic social media use were often different for men and women. Other variables may also play a role, such as nighttime-specific use, emotional involvement, and whether the individual behaves as an active or passive user. Evidence from this review provides a solid base for recommending cautious use of social media. Intense use and unhealthy habits, evidenced by addiction symptoms, may be problematic in less resilient individuals.

Microcephaly measurement in adults and its association with clinical variables.

OBJECTIVE: To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining. METHODS: In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly measured. A linear regression was used to determine the association of head circumference with brain volume and clinical variables. Microcephaly was defined as head circumference that were two standard deviations below the mean of significant clinical variables. We further applied an association rule mining to find rules associating microcephaly with several sociodemographic and clinical variables. RESULTS: In our sample of 2,508 adults, the mean head circumference was 55.3 ± 2.7cm. Head circumference was related to height, cerebral volume, and sex (p < 0.001 for all). Microcephaly was present in 4.7% of the sample (n = 119). Out of 34,355 association rules, we found significant relationships between microcephaly and a clinical dementia rating (CDR) > 0.5 with an informant questionnaire on cognitive decline in the elderly (IQCODE) ≥ 3.4 (confidence: 100% and lift: 5.6), between microcephaly and a CDR > 0.5 with age over 70 years (confidence: 42% and lift: 2.4), and microcephaly and males (confidence: 68.1% and lift: 1.3). CONCLUSION: Head circumference was related to cerebral volume. Due to its low cost and easy use, head circumference can be used as a screening test for microcephaly, adjusting it for gender and height. Microcephaly was associated with dementia at old age.

Optimizing the CAMCOG test in the screening for mild cognitive impairment and incipient dementia: saving time with relevant domains.

OBJECTIVE: To identify the CAMCOG sub-items that best contribute for the identification of patients with mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD) in clinical practice. METHODS: Cross-sectional assessment of 272 older adults (98 MCI, 82 AD, and 92 controls) with a standardized neuropsychological battery and the CAMCOG schedule. Backward logistic regression analysis with diagnosis (MCI and controls) as dependent variable and the sub-items of the CAMCOG as independent variable was carried out to determine the CAMCOG sub-items that predicted the diagnosis of MCI. RESULTS: Lower scores on Language, Memory, Praxis, and Calculation CAMCOG sub-items were significantly associated with the diagnosis of MCI. A composite score obtained by the sum of these scores significantly discriminated MCI patients from comparison groups. This reduced version of the CAMCOG showed similar diagnostic accuracy than the original schedule for the identification of patients with MCI as compared to controls (AUC = 0.80 ± 0.03 for the reduced CAMCOG; AUC = 0.79 ± 0.03 for the original CAMCOG). CONCLUSION: This reduced version of the CAMCOG had similar diagnostic properties as the original CAMCOG and was faster and easier to administer, rendering it more suitable for the screening of subtle cognitive deficits in general clinical practice.

Mental health in medical students during COVID-19 quarantine: a comprehensive analysis across year-classes.

OBJECTIVES: The COVID-19 pandemic brought abrupt changes when quarantine measures were implemented. Most medical students had distance learning as their main content delivery mode, but in clerkship (fifth and sixth years), in-person activities were maintained under new protocols. These different modes may have affected student mental health. This study examines mental burden and empathy in medical students during the beginning of the COVID-19 pandemic according to the year of attendance. METHODS: All students attending first to the sixth year in the same medical school were invited to participate. The Hospital Anxiety and Depression Scale (HADS), the Self-Reporting Questionnaire (SRQ-20), the Interpersonal Reactivity Index (IRI), and the Mindful Attention Awareness Scale (MAAS) were provided. RESULTS: HADS scores for Anxiety and Depression (n=347) were 9.8±4.3 and 7.1±3.6, respectively; the SRQ-20 (n=373) score was 8.1±4.5; all scores were negatively correlated with the year of attendance. IRI (n=373) scores were: 2.6±0.5 (Empathic Concern), 2.7±0.7 (Perspective Taking), 2.5±0.9 (Fantasy), and 1.7±0.7 (Personal Distress). Fantasy was negatively correlated with the year of attendance. MAAS scores were positively correlated with the year of attendance. Worse mental health scores were found for first-year students across all scales. CONCLUSIONS: We found high levels of mental burden in medical students in the early period of the COVID-19 pandemic, especially in first-year students, who may have fewer resources to deal with stress. Moreover, as they entered college a short time before the pandemic, they were unable to experience academic life fully or create important new social support networks to deal with adversities.

ß-amyloid pathology is not associated with depression in a large community sample autopsy study.

BACKGROUND: Depression has been associated with dementia. This study aimed to verify if ß-amyloid Alzheimer's disease-type burden was associated with lifetime major depressive disorder (MDD) and with current depressive symptoms in a large population-based autopsy study. METHODS: We included 1013 deceased subjects submitted to autopsy (mean age=74.3±11.6 years, 49% men) in a community sample. ß-amyloid burden was measured in all cases based on the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for presence and density of neuritic plaques. Lifetime MDD was defined when at least one previous episode according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders - DSM (SCID). Depressive symptoms and cognitive impairment were determined using the depression item of the Neuropsychiatric Inventory (D-NPI>0) and the Clinical Dementia Rating scale (CDR>0.5) respectively. RESULTS: Lifetime MDD, late life depression (LLD) and current depressive symptoms were associated with cognitive impairment (p<0.001). Additionally, neuritic plaques were associated with cognitive impairment (p<0.001). Moderate or frequent neurite plaque density was not associated with MDD, LLD or current depressive symptoms in multiple logistic models adjusted for age, gender, and cognitive impairment. LIMITATIONS: In this cross-sectional study, all neuropsychiatric and cognitive assessment were based on informant-report of deceased participants. CONCLUSIONS: Different clinical depictions of depression were associated with dementia in this large community sample of elderly individuals with multiethnic backgrounds. Notwithstanding, they were unrelated to ß-amyloid pathology in the brain areas studied. The link between depression and dementia might be complex and determined by multiple factors.

Psychometric characteristics of the Rivermead Behavioural Memory Test (RBMT) as an early detection instrument for dementia and mild cognitive impairment in Brazil.

BACKGROUND: The Rivermead Behavioural Memory Test (RBMT) assesses everyday memory by means of tasks which mimic daily challenges. The objective was to examine the validity of the Brazilian version of the RBMT to detect cognitive decline. METHODS: 195 older adults were diagnosed as normal controls (NC) or with mild cognitive impairment (MCI) or Alzheimer's disease (AD) by a multidisciplinary team, after participants completed clinical and neuropsychological protocols. RESULTS: Cronbach's alpha was high for the total sample for the RBMT profile (PS) and screening scores (SS) (PS = 0.91, SS = 0.87) and for the AD group (PS = 0.84, SS = 0.85), and moderate for the MCI (PS = 0.62, SS = 0.55) and NC (PS = 0.62, SS = 0.60) groups. RBMT total scores, Appointment, Pictures, Immediate and Delayed Story, Immediate and Delayed Route, Delayed Message and Date contributed to differentiate NC from MCI. ROC curve analyses indicated high accuracy to differentiate NC from AD patients, and, moderate accuracy to differentiate NC from MCI. CONCLUSIONS: The Brazilian version of the RBMT seems to be an appropriate instrument to identify memory decline in Brazilian older adults.

Diagnosis of mild cognitive impairment revisited after one year. Preliminary results of a prospective study.

BACKGROUND/AIMS: The diagnostic stability of mild cognitive impairment (MCI) on short-term follow-up is a key issue in the characterization of this clinical syndrome. We aim to determine the cognitive outcome after 1 year of follow-up in a cohort of older adults. METHODS: Baseline clinical and neuropsychological assessments were carried out in older subjects recruited at a tertiary memory clinic. The subjects were reassessed after 1 year of follow-up with the same clinical and neuropsychological protocol. RESULTS: A total of 115 older adults, including MCI (n = 54) and controls (n = 61), underwent baseline and follow-up evaluation. Ten subjects classified as MCI at baseline (23%) resumed normal cognitive function and 13 controls (21%) progressed to MCI upon follow-up (chi(2) = 0.015, d.f. = 1, p = 0.90). The subjects diagnosed as having MCI on both assessments were older (p = 0.002) and had a worse global cognitive performance according to the Cambridge Cognitive Test (p = 0.014). CONCLUSION: The subjects who maintain the MCI status are older and have a worse baseline cognitive performance as well as multiple cognitive deficits.

Neuropsychiatric Inventory in Community-Dwelling Older Adults with Mild Cognitive Impairment and Dementia.

BACKGROUND: Behavioral and psychological symptoms (BPSD) can be a prodrome of dementia, and the Neuropsychiatric Inventory (NPI) is widely used for BPSD evaluation. OBJECTIVE: To compare the prevalence of BPSD according to cognitive status, and to determine NPI cutoffs that best discern individuals with mild cognitive impairment (MCI) and dementia from those without dementia. METHODS: We included 1,565 participants (mean age = 72.7±12.2 years, 48% male). BPSD and cognitive status were assessed with the NPI and the Clinical Dementia Rating (CDR). We used multivariable logistic regression models to investigate the association of BPSD with cognitive status. The area under the curve (AUC) was used to assess model discrimination, and to determine the best NPI cutoff for MCI and dementia. RESULTS: Participants were cognitively normal (CDR = 0; n = 1,062), MCI (CDR = 0.5; n = 145), or dementia (CDR≥1.0, n = 358). NPI symptoms were more frequent in dementia and MCI when compared to cognitively normal. Higher odds for delusions, hallucinations, disinhibition, and psychomotor alterations were found among participants with dementia and MCI than in those who were cognitively normal. The best NPI cutoff to discern participants with dementia from those cognitively normal was 11 (AUC = 0.755). Poor discrimination (AUC = 0.563) was found for the comparison of MCI and those cognitively normal. CONCLUSIONS: We found an increase in BPSD frequencies across the continuum of cognitive impairment. BPSD severity and frequency in MCI was more similar to individuals cognitively normal than with dementia. NPI scores≥to 11 in individuals with no diagnosis of dementia can support the decision for further investigation of dementia.

Combining functional scales and cognitive tests in screening for mild cognitive impairment at a university-based memory clinic in Brazil.

OBJECTIVE: To determine the diagnostic accuracy of the Mini-Mental State Examination combined to the Informant Questionnaire on Cognitive Decline in the Elderly for the identification of mild cognitive impairment. METHOD: 191 elderly subjects were assessed with the Mini-Mental State Examination, and their informants were assessed with the Informant Questionnaire on Cognitive Decline in the Elderly. Subjects were divided into three groups according to their cognitive state (controls: n = 67, mild cognitive impairment: n = 65 and dementia: n = 59), which was ascertained by clinical and neuropsychological evaluation. The diagnostic accuracy of each test in the discrimination of diagnostic groups (mild cognitive impairment vs. controls, mild cognitive impairment vs. dementia and dementia vs. controls) was examined with the aid of ROC curves. We additionally verified if the combination of both tests would increase diagnostic accuracy for mild cognitive impairment and control identification. RESULTS: The combination of the Mini-Mental State Examination and the Informant Questionnaire on Cognitive Decline in the Elderly scores did not increase the Mini-Mental State Examination diagnostic accuracy in the identification of patients with mild cognitive impairment. CONCLUSIONS: The present data do not warrant the combination of the Mini-Mental State Examination and the Informant Questionnaire on Cognitive Decline in the Elderly as a sufficient diagnostic tool in the diagnostic screening for mild cognitive impairment.

Mild cognitive impairment: cognitive screening or neuropsychological assessment?

OBJECTIVE: To describe the neuropsychological profile of mild cognitive impairment subtypes (amnestic, non-amnestic and multiple-domain) of a clinical sample. We further address the diagnostic properties of the Mini-Mental State Examination and the Cambridge Cognitive Examination for the identification of the different mild cognitive impairment subtypes in clinical practice. METHOD: Cross-sectional clinical and neuropsychological evaluation of 249 elderly patients attending a memory clinic at a university hospital in Sao Paulo, Brazil. RESULTS: The performance of patients with mild cognitive impairment was heterogeneous across the different subtests of the neuropsychological battery, with a trend towards an overall worse performance for amnestic (particularly multiple domain) mild cognitive impairment as compared to non-amnestic subtypes. Screening tests for dementia (Mini-Mental State Examination and Cambridge Cognitive Examination) adequately discriminated cases of mild Alzheimer's disease from controls, but they were not accurate to discriminate patients with mild cognitive impairment (all subtypes) from control subjects. CONCLUSIONS: The discrimination of mild cognitive impairment subtypes was possible only with the aid of a comprehensive neuropsychological assessment. It is necessary to develop new strategies for mild cognitive impairment screening in clinical practice.

Low brain-derived neurotrophic factor levels in post-mortem brains of older adults with depression and dementia in a large clinicopathological sample.

BACKGROUND: Disturbances in peripheral brain-derived neurotrophic factor (BDNF) have been reported in major depressive disorder (MDD). However, there are no studies measuring BDNF levels directly in post-mortem brains of older subjects with MDD and dementia. We aimed to verify if brain BDNF levels were lower in older adults with lifetime history of MDD with and without dementia. METHODS: BDNF levels of post-mortem brains from 80 community-dwelling older individuals with lifetime MDD with and without dementia were compared with levels from 80 controls without lifetime MDD. Participants with no reliable close informant, or with prolonged agonal state were excluded. Lifetime MDD was defined as at least one previous episode according to the Structured Clinical Interview for DSM (SCID). RESULTS: BDNF levels were lower in the MDD group with dementia than in participants with dementia and without MDD as confirmed by multivariate analysis adjusted for clinical and cardiovascular risk factors (ß = -0.106, 95%CI = -0.204; -0.009, p = 0.034). No difference was found in the group with MDD without dementia compared with their controls. LIMITATIONS: The retrospective assessment of a lifetime history of depression may be subject to information bias and this study only establishes a cross-sectional association between lifetime history of MDD and lower levels of BDNF in patients with dementia. CONCLUSIONS: In this community sample of older individuals, lower brain BDNF levels were found in cases with both lifetime MDD and dementia. Low BDNF levels could be a moderator to accelerated brain aging observed in MDD with dementia.

Microcephaly measurement in adults and its association with clinical variables

ABSTRACT OBJECTIVE To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining. METHODS In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly measured. A linear regression was used to determine the association of head circumference with brain volume and clinical variables. Microcephaly was defined as head circumference that were two standard deviations below the mean of significant clinical variables. We further applied an association rule mining to find rules associating microcephaly with several sociodemographic and clinical variables. RESULTS In our sample of 2,508 adults, the mean head circumference was 55.3 ± 2.7cm. Head circumference was related to height, cerebral volume, and sex (p < 0.001 for all). Microcephaly was present in 4.7% of the sample (n = 119). Out of 34,355 association rules, we found significant relationships between microcephaly and a clinical dementia rating (CDR) > 0.5 with an informant questionnaire on cognitive decline in the elderly (IQCODE) ≥ 3.4 (confidence: 100% and lift: 5.6), between microcephaly and a CDR > 0.5 with age over 70 years (confidence: 42% and lift: 2.4), and microcephaly and males (confidence: 68.1% and lift: 1.3). CONCLUSION Head circumference was related to cerebral volume. Due to its low cost and easy use, head circumference can be used as a screening test for microcephaly, adjusting it for gender and height. Microcephaly was associated with dementia at old age.