The association of white matter connectivity with prevalence, incidence and course of depressive symptoms: The Maastricht Study.

BACKGROUND: Altered white matter brain connectivity has been linked to depression. The aim of this study was to investigate the association of markers of white matter connectivity with prevalence, incidence and course of depressive symptoms. METHODS: Markers of white matter connectivity (node degree, clustering coefficient, local efficiency, characteristic path length, and global efficiency) were assessed at baseline by 3 T MRI in the population-based Maastricht Study (n = 4866; mean ± standard deviation age 59.6 ± 8.5 years, 49.0% women; 17 406 person-years of follow-up). Depressive symptoms (9-item Patient Health Questionnaire; PHQ-9) were assessed at baseline and annually over seven years of follow-up. Major depressive disorder (MDD) was assessed with the Mini-International Neuropsychiatric Interview at baseline only. We used negative binominal, logistic and Cox regression analyses, and adjusted for demographic, cardiovascular, and lifestyle risk factors. RESULTS: A lower global average node degree at baseline was associated with the prevalence and persistence of clinically relevant depressive symptoms [PHQ-9 ⩾ 10; OR (95% confidence interval) per standard deviation = 1.21 (1.05-1.39) and OR = 1.21 (1.02-1.44), respectively], after full adjustment. On the contrary, no associations were found of global average node degree with the MDD at baseline [OR 1.12 (0.94-1.32) nor incidence or remission of clinically relevant depressive symptoms [HR = 1.05 (0.95-1.17) and OR 1.08 (0.83-1.41), respectively]. Other connectivity measures of white matter organization were not associated with depression. CONCLUSIONS: Our findings suggest that fewer white matter connections may contribute to prevalent depressive symptoms and its persistence but not to incident depression. Future studies are needed to replicate our findings.

The effects of selective serotonin reuptake inhibitors on memory functioning in older adults: A systematic literature review.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to older adults. In contrast to young subjects, it is unclear whether older adults may be vulnerable to cognitive side effects. Serotonin is involved in cognitive functions (e.g. memory). It is of great importance to examine the effects of SSRIs on memory functioning in older adults. OBJECTIVES: The objective of this systematic literature review is to summarize studies in which the effects of SSRI treatment on all aspects of memory functioning in older adults are investigated. METHODS: PubMed, PsycINFO, CINAHL, and Embase were searched for all studies published until 18th of October 2021. Articles were included if they fulfilled the inclusion criteria as follows: (1) study design is (randomized) controlled trial, cross-sectional, or prospective cohort study; (2) study population consists of older adults (mean age ⩾65 years), or results for this age-group are reported separately; (3) intervention is use of an SSRI; and (4) effects on performance of any memory domain are measured and clearly described. RESULTS: The search yielded 1888 articles, of which 136 were included for the full-text review. Eventually, 40 articles were included. Most studies reported no association between SSRI use and memory functioning. The studies that found a positive association mainly investigated older adults with mental or neurological disorders (e.g. depression or stroke). A few studies found a negative association in the following subgroups: non-responders (depression), patients with frontal brain disease, and women. CONCLUSION: Overall, no consistent negative effects of SSRIs on memory functioning in older adults were found after SSRI treatment. Most studies reported no change in memory functioning after SSRI use. Some studies even showed an improvement in memory performance. Positive effects of SSRIs on memory functioning were especially found in older adults with mental or neurological disorders, such as subjects with depression or stroke.

A Scoping Review of Communicating Neuropsychological Test Results to Patients and Family Members.

Feedback of neuropsychological test results to patients and family members include psychoeducation and implications for daily life. This scoping review aimed to provide an overview of the literature on neuropsychological feedback and to offer clinical recommendations. In accordance with formal scoping review methodology, PubMed, PsycInfo, Web of Science, CINAHL, and Embase databases were searched. Studies were included if they reported on neuropsychological feedback, if full papers were available, and if they included human participants. All languages were included, and no limit was placed on the year of publication. Of the 2,173 records screened, 34 publications met the inclusion criteria. Five additional publications were included after cross-referencing. An update of the search led to the inclusion of two additional papers. Of these 41 publications, 26 were research papers. Neuropsychological feedback is provided for a wide spectrum of diagnoses and usually given in-person and has been related to optimal a positive effect on patient outcomes (e.g. increase the quality of life). Most papers reported on satisfaction and found that satisfaction with an NPA increased when useful feedback was provided. However, information retention was found to be low, but communication aids, such as written information, were found to be helpful in improving retention. The current review demonstrated the benefits of neuropsychological feedback and that this should be part of standard clinical procedures when conducting a neuropsychological assessment. Further research on the benefits of neuropsychological feedback and how to improve information provision would enrich the neuropsychological literature.

Interaction of caregiver-expressed emotions and neuropsychiatric symptoms in persons with dementia: a longitudinal cohort study.

OBJECTIVES: Neuropsychiatric symptoms (NPS) have a major impact in persons with dementia (PwD). The interaction between the caregiver and the person with dementia may be related to the emergence of NPS. The concept of expressed emotion (EE) is used to capture this dyadic interaction. The aim of the present study is to examine longitudinally the association between EE in caregivers and NPS in PwD living at home. DESIGN: A longitudinal cohort study with 2 years of follow-up. SETTING: PwD and their informal caregivers living at home in the south of the Netherlands. PARTICIPANTS: 112 dyads of PwD and their caregivers from the MAAstricht Study of BEhavior in Dementia. MAIN OUTCOME MEASURES: EE was measured at baseline with the Five-Minute Speech Sample and was used to classify caregivers in a low-EE or high-EE group. Associations between EE and neuropsychiatric subsyndromes (hyperactivity, mood and psychosis) measured with the Neuropsychiatric Inventory (NPI) were analysed over time. RESULTS: Seventy-six (67.9%) caregivers were classified in the low-EE group and 36 (32.1%) in the high-EE group. There was no difference between the EE groups in mean NPI scores over time. In the high-EE group, hyperactivity occurred more frequently than in the low-EE group at baseline (p=0.013) and at the other time points, but the mean difference was not always significant. There were no differences for the mood and psychosis subsyndromes. PwD with caregivers scoring high on the EE subcategory critical comments had an increased risk of institutionalisation (OR 6.07 (95% CI 1.14 to 32.14, p=0.034)) in comparison with caregivers scoring low on critical comments. CONCLUSIONS: High EE in informal caregivers is associated with hyperactivity symptoms in PwD. This association is likely to be bidirectional. Future studies investigating this association and possible interventions to reduce EE are needed.

The association of markers of cerebral small vessel disease and brain atrophy with incidence and course of depressive symptoms - the maastricht study.

BACKGROUND: Cerebral small vessel disease (CSVD) and neurodegeneration may be involved in the development and persistence of late-life depressive symptoms, but longitudinal evidence is scarce. We investigated the longitudinal associations of markers of CSVD and brain atrophy with incident depressive symptoms and the course of depressive symptoms, above and below 60 years of age. METHODS: White matter hyperintensity volumes (WMH), presence of lacunar infarcts and cerebral microbleeds, and white matter, grey matter, and cerebral spinal fluid volumes were assessed at baseline by 3T MRI in The Maastricht Study (mean age 59.5±8.5 years, 49.6% women, n=4,347; 16,535 person-years of follow-up). Clinically relevant depressive symptoms (9-item Patient Health Questionnaire≥10) were assessed at baseline and annually over seven years. We used Cox regression and multinomial logistic regression analyses adjusted for demographic, cardiovascular, and lifestyle risk factors. RESULTS: Above 60 years of age, larger WMH volumes were associated with an increased risk for incident depressive symptoms (HR[95%CI]:1.24[1.04;1.48] per SD) and a persistent course of depressive symptoms (OR:1.44[1.04;2.00] per SD). Total CSVD burden was associated with persistent depressive symptoms irrespective of age (adjusted OR:1.58[1.03;2.43]), while no associations were found for general markers of brain atrophy. LIMITATIONSS: Our findings need replication in other large-scale population-based studies. CONCLUSIONS: Our findings may suggest a temporal association of larger WMH volume with the incidence and persistence of late-life depression in the general population and may provide a potential target for the prevention of chronic late-life depression.

Dynamic behavior of the locus coeruleus during arousal-related memory processing in a multi-modal 7T fMRI paradigm.

A body of animal and human evidence points to the norepinephrine (NE) locus coeruleus (LC) system in modulating memory for arousing experiences, but whether the LC would recast its role along memory stages remains unknown. Sedation precluded examination of LC dynamics during memory processing in animals. Here, we addressed the contribution of the LC during arousal-associated memory processing through a unique combination of dedicated ultra-high-field LC-imaging methods, a well-established emotional memory task, online physiological and saliva alpha-amylase measurements in young adults. Arousal-related LC activation followed amygdala engagement during encoding. During consolidation and recollection, activation transitioned to hippocampal involvement, reflecting learning and model updating. NE-LC activation is dynamic, plays an arousal-controlling role, and is not sufficient but requires interactions with the amygdala to form adaptive memories of emotional experiences. These findings have implications for understanding contributions of LC dysregulation to disruptions in emotional memory formation, observed in psychiatric and neurocognitive disorders.

Imaging markers associated with the development of post-stroke depression and apathy: Results of the Cognition and Affect after Stroke - a Prospective Evaluation of Risks study.

INTRODUCTION: It has been suggested that the development of post-stroke apathy (PSA) and depression (PSD) may be more strongly associated with generalised brain pathology, rather than the stroke lesion itself. The present study aimed to investigate associations between imaging markers of lesion-related and generalised brain pathology and the development of PSA and PSD during a one-year follow-up. PATIENTS AND METHODS: In a prospective cohort study, 188 stroke patients received 3-Tesla MRI at baseline (three months post-stroke) for evaluation of lesion-related, vascular, and degenerative brain pathology. Presence of lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces was summed to provide a measure of total cerebral small vessel disease (cSVD) burden (range 0-4). The Mini International Neuropsychiatric Interview and Apathy Evaluation Scale were administered at baseline and repeated at 6- and 12-month follow-up to define presence of PSD and PSA, respectively. RESULTS: Population-averaged logistic regression models showed that global brain atrophy and severe cSVD burden (score 3-4) were significantly associated with the odds of having PSA (ORGEE 5.33, 95% CI 1.99-14.25 and 3.04, 95% CI 1.20-7.69, respectively), independent of stroke lesion volume and co-morbid PSD. Medium cSVD burden (score 2) was significantly associated with the odds of having PSD (ORGEE 2.92, 95% CI 1.09-7.78), independent of stroke lesion volume, co-morbid PSA, and pre-stroke depression. No associations were found with lesion-related markers. CONCLUSIONS: The results suggest that generalised degenerative and vascular brain pathology, rather than lesion-related pathology, is an important predictor for the development of PSA, and less strongly for PSD.

Effectiveness of a Blended Care Self-Management Program for Caregivers of People With Early-Stage Dementia (Partner in Balance): Randomized Controlled Trial.

BACKGROUND: The benefits of electronic health support for dementia caregivers are increasingly recognized. Reaching caregivers of people with early-stage dementia could prevent high levels of burden and psychological problems in the later stages. OBJECTIVE: The current study evaluates the effectiveness of the blended care self-management program, Partner in Balance, compared to a control group. METHODS: A single-blind randomized controlled trial with 81 family caregivers of community-dwelling people with mild dementia was conducted. Participants were randomly assigned to either the 8-week, blended care self-management Partner in Balance program (N=41) or a waiting-list control group (N=40) receiving usual care (low-frequent counseling). The program combines face-to-face coaching with tailored Web-based modules. Data were collected at baseline and after 8 weeks in writing by an independent research assistant who was blinded to the treatment. The primary proximal outcome was self-efficacy (Caregiver Self-Efficacy Scale) and the primary distal outcome was symptoms of depression (Center for Epidemiological Studies Depression Scale). Secondary outcomes included mastery (Pearlin Mastery Scale), quality of life (Investigation Choice Experiments for the Preferences of Older People), and psychological complaints (Hospital Anxiety and Depression Scale-Anxiety and Perceived Stress Scale). RESULTS: A significant increase in favor of the intervention group was demonstrated for self-efficacy (care management, P=.002; service use P=.001), mastery (P=.001), and quality of life (P=.032). Effect sizes were medium for quality of life (d=0.58) and high for self-efficacy care management and service use (d=0.85 and d=0.93, respectively) and mastery (d=0.94). No significant differences between the groups were found on depressive symptoms, anxiety, and perceived stress. CONCLUSIONS: This study evaluated the first blended-care intervention for caregivers of people with early-stage dementia and demonstrated a significant improvement in self-efficacy, mastery, and quality of life after receiving the Partner in Balance intervention, compared to a waiting-list control group receiving care as usual. Contrary to our expectations, the intervention did not decrease symptoms of depression, anxiety, or perceived stress. However, the levels of psychological complaints were relatively low in the study sample. Future studies including long-term follow up could clarify if an increase in self-efficacy results in a decrease or prevention of increased stress and depression. To conclude, the program can provide accessible preventative care to future generations of caregivers of people with early-stage dementia. TRIAL REGISTRATION: Netherlands Trial Register NTR4748; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4748 (Archived by WebCite at http://www.webcitation.org/6vSb2t9Mg).

Implementation of the Blended Care Self-Management Program for Caregivers of People With Early-Stage Dementia (Partner in Balance): Process Evaluation of a Randomized Controlled Trial.

BACKGROUND: Caring for a family member with dementia puts caregivers at risk of overburdening. Electronic health (eHealth) support for caregivers offers an opportunity for accessible tailored interventions. The blended care self-management program "Partner in Balance" (PiB) for early-stage dementia caregivers was executed in Dutch dementia care organizations. The program combines face-to-face coaching with tailored Web-based modules. Next to an evaluation of program effectiveness, an evaluation of sampling and intervention quality is essential for the generalizability and interpretation of results. OBJECTIVE: The aim of this study was to describe the process evaluation from the perspective of both family caregivers (participants) and professionals delivering the intervention (coaches) to determine internal and external validity before the effect analysis and aid future implementation. METHODS: Implementation, sampling, and intervention quality were evaluated with quantitative and qualitative data from logistical research data, coach questionnaires (n=13), and interviews with coaches (n=10) and participants (n=49). Goal attainment scaling was used to measure treatment-induced change. Analyses were performed with descriptive statistics and deductive content analysis. RESULTS: The participation rate of eligible caregivers was 51.9% (80/154). Recruitment barriers were lack of computer and lack of need for support. Young age and employment were considered recruitment facilitators. All coaches attended training and supervision in blended care self-management. Deviations from the structured protocol were reported on intervention time, structure, and feedback. Coaches described an intensified relationship with the caregiver post intervention. Caregivers appreciated the tailored content and positive feedback. The blended structure increased their openness. The discussion forum was appreciated less. Overall, personal goals were attained after the program (T>50). Implementation barriers included lack of financing, time, and deviating target population. CONCLUSIONS: Participants and coaches were satisfied with the intervention, but adapting the content to specific subgroups, for example, younger caregivers, was recommended. Implementation of the program requires more awareness of the benefits of blended care self-management programs and training in tailored self-management skills. TRIAL REGISTRATION: Dutch Trial Register (NTR): NTR4748; http://www.trialregister.nl (Archived by WebCite at http://www.webcitation.org/6vSb2t9Mg).

Development and Initial Evaluation of the Web-Based Self-Management Program "Partner in Balance" for Family Caregivers of People With Early Stage Dementia: An Exploratory Mixed-Methods Study.

BACKGROUND: People with dementia increasingly depend on informal caregivers. Internet-based self-management interventions hold considerable promise for meeting the educational and support needs of early stage dementia caregivers (EDCs) at a reduced cost. OBJECTIVE: This study aimed to (1) develop an online self-management program for EDC to increase self-efficacy and goal attainment, and (2) evaluate the program's feasibility and report preliminary data on effectiveness. METHODS: Based on the Medical Research Council (MRC) framework for the development and evaluation of complex interventions, a stepwise approach was adopted to explore potential user needs and develop and validate the content by means of (1) focus group discussions with dementia caregivers (N=28), (2) interviews with dementia care professionals (N=11), and (3) individual think-aloud usability tests with EDC (N=2) and experts (N=2). A pilot evaluation was conducted with EDC (N=17) to test the feasibility and establish preliminary effects. Self-report measures of feasibility were completed after the completion of intervention. Self-efficacy and goal attainment were evaluated before and after the intervention. RESULTS: The different steps provided useful information about the needs of potential users regarding the content and delivery of the program. This resulted in the newly developed "Partner in Balance" program. At the start, system failures resulted in a high noncompleter rate (7/17, 41%), but at the end, an acceptable feasibility score of 209 (range 54-234) was found. The convenience of completing the program at home, the tailored content, and the guidance (face-to-face and online) were appraised positively. Preliminary effects on caregiver self-efficacy (P<.05) and goal attainment (T>50) were promising. CONCLUSIONS: Adaptations were made to the program to limit the amount of system failures and prevent high noncompleter rates. As recommended by the MRC framework, confirming the feasibility and preliminary effectiveness is a valuable step toward examining the effectiveness of this newly developed intervention. TRIAL REGISTRATION: Dutch Trial Register (NTR): NTR4217; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4217 (Archived by WebCite at http://www.webcitation.org/6f6B8lvRP).