Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models and tractometry.

Late-life depression (LLD) is both common and disabling and doubles the risk of dementia onset. Apathy might constitute an additional risk of cognitive decline but clear understanding of its pathophysiology is lacking. While white matter (WM) alterations have been assessed using diffusion tensor imaging (DTI), this model cannot accurately represent WM microstructure. We hypothesized that a more complex multi-compartment model would provide new biomarkers of LLD and apathy. Fifty-six individuals (LLD n = 35, 26 females, 75.2 ± 6.4 years, apathy evaluation scale scores (41.8 ± 8.7) and Healthy controls, n = 21, 16 females, 74.7 ± 5.2 years) were included. In this article, a tract-based approach was conducted to investigate novel diffusion model biomarkers of LLD and apathy by interpolating microstructural metrics directly along the fiber bundle. We performed multivariate statistical analysis, combined with principal component analysis for dimensional data reduction. We then tested the utility of our framework by demonstrating classically reported from the literature modifications in LDD while reporting new results of biological-basis of apathy in LLD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fiber bundles. Our study suggests that new fiber bundles, such as the striato-premotor tracts, may be involved in LLD and apathy, which bring new light of apathy mechanisms in major depression. We also identified statistical changes in diffusion MRI metrics in 5 different tracts, previously reported in major cognitive disorders dementia, suggesting that these alterations among these tracts are both involved in motivation and cognition and might explain how apathy is a prodromal phase of degenerative disorders.

Late Life Depression is Not Associated With Alzheimer-Type Tau: Preliminary Evidence From a Next-Generation Tau Ligand PET-MR Study.

OBJECTIVE: To investigate whether tau accumulation is higher in late life depression (LLD) compared to non-depressed cognitively unimpaired (CU) older adults. To situate these findings in the neurodegeneration model of LLD by assessing group differences in tau and grey matter volume (GMV) between LLD, non-depressed CU and mild cognitive impairment due to Alzheimer's Disease (MCI). DESIGN: Monocentric, cross-sectional study. SETTING: University Psychiatric hospital, memory clinic and outpatient neurology practice. PARTICIPANTS: A total of 102 adults over age 60, of whom 19 currently depressed participants with LLD, 19 with MCI and 36 non-depressed CU participants completed neuropsychological testing and tau PET-MR imaging. MEASUREMENTS: PET-MRI: 18F-MK-6240 tracer SUVR for tau assessment; 3D T1-weighted structural MRI derived GMV in seven brain regions (temporal, cingulate, prefrontal and parietal regions); amyloid PET to assess amyloid positivity; Neuropsychological test scores: MMSE, RAVLT, GDS, MADRS. ANCOVA and Spearman's rank correlations to investigate group differences in tau and GMV, and correlations with neuropsychological test scores respectively. RESULTS: Compared to non-depressed CU participants, LLD patients showed lower GMV in temporal and anterior cingulate regions but similar tau accumulation and amyloid positivity rate. In contrast, MCI patients had significantly higher tau accumulation in all regions. Tau did not correlate with any neuropsychological test scores in LLD. CONCLUSION: Our findings suggest AD-type tau is not higher in LLD compared to non-depressed, cognitively unimpaired older adults and appears unlikely to contribute to lower gray matter volume in LLD, further underscoring the need to distinguish major depressive disorder from depressive symptoms occurring in early AD.

Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression with 11C-PiB beta-amyloid PET and 7T magnetic resonance spectroscopy.

Positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer's disease (AD)-mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aß) PET and 7 T 1H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aß, and cognitive scores, and whether metabolites and Aß explained cognitive scores better than Aß alone. In the ACC, higher Aß was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aß deposition than by models that only included one of these variables. These findings identify preliminary associations between Aß, neurometabolites, and cognition.

Efficacy and Side Effects of Mixed-Strategy Electroconvulsive Therapy: A Proof-of-Concept Randomized Clinical Trial on Late Life Depression.

OBJECTIVE: Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient's resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects. METHODS: This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. RESULTS: In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). CONCLUSION: msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

Participation in Physical, Cognitive, and Social Activities and the Association with Mobility Disability Transitions in Older Adults.

Development of late-life mobility disability is a dynamic process of transitions between worsening and improving. We tested associations between participation in physical, social, and cognitive activity with mobility disability transitions. Participants (N=2,758, age 78.1 years [SD: 7.7]) from two Rush Alzheimer's Disease Center cohorts completed annual mobility disability questionnaires for 7.6 (SD: 4.4) years. First-order Markov transition models tested associations between baseline self-reported physical, social, and cognitive activity with bidirectional transitions in mobility disability score increases (worsening) and decreases (improving) between consecutive visits. Overall, 75.5% of participants experienced ≥1 transition among 18,318 pairs of consecutive visits-4,174 of which were worsening and 2,606 were improving transitions. Adjusting for covariates, higher participation in each activity type was associated with lower odds of worsening (physical OR=0.71, 95% CI: 0.67-0.75; social OR=0.64, 95% CI: 0.58-0.70; and cognitive OR=0.79, 95% CI: 0.74-0.85), and higher odds of improving (physical OR=1.20, 95% CI: 1.11-1.28; social OR=1.45, 95% CI: 1.30-1.61; and cognitive OR=1.12, 95% CI: 1.03-1.22) in separate models. In combined models, physical and social activity remained associated with worsening and improving; cognitive activity was only associated with worsening. Physical, social, and cognitive activity engagement contributes to lower odds of worsening mobility disability and may promote recovery.

Cognitive Profiles in Treatment-Resistant Late-Life Depression and their Impact on Treatment Outcomes.

BACKGROUND: Late-life depression (LLD) is associated with cognitive impairment, yet substantial heterogeneity exists among patients. Data on the extent of cognitive impairments is inconclusive, particularly in patients with treatment-resistant depression (TRD). We investigated the cognitive profiles of patients with treatment-resistant vs. nonresistant LLD and aimed to identify distinct cognitive subgroups. Additionally, we examined whether cognitive subgroups differentially responded to treatment with bilateral repetitive transcranial magnetic stimulation (rTMS). METHODS: 165 patients with LLD were divided into treatment-resistant and nonresistant groups and compared to healthy controls (HC) on measures of executive function, information processing speed, verbal learning, and memory. Cluster analysis identified subgroups based on cognitive scores. Demographic and clinical variables, as well as outcomes with bilateral rTMS, were compared between cognitive subgroups. RESULTS: Patients with LLD, particularly TRD, exhibited significantly worse cognitive performance than HC. A three-cluster solution was found, including "Cognitively Intact" (n = 89), "Cognitively Diminished" (n = 29), and "Impaired Memory" (n = 47) subgroups. Both the "Cognitively Diminished" and "Impaired Memory" subgroups had more anxiety symptoms and a higher proportion of patients with TRD than the "Cognitively Intact" group, though the latter did not survive multiple comparison correction. No significant differences were observed in outcomes to rTMS treatment. CONCLUSIONS: Patients with LLD exhibited impairments across cognitive domains, which were more pronounced in TRD. Three identified cognitive subgroups responded similarly to rTMS treatment, indicating its effectiveness across cognitive profiles, especially when medications are not tolerated. Future research should examine the relationship among cognitive subgroups, cognitive decline, and neurodegeneration.

Altered activation of the dorsal anterior cingulate cortex during oddball performance in individuals at risk for Alzheimer's disease.

INTRODUCTION: The neural mechanisms underlying neurodegenerative disorders in the elderly remain elusive, despite extensive neuroimaging research in recent decades. Amnestic type mild cognitive impairment (aMCI) and late-life major depressive disorder (MDD) are two such conditions characterized by intersecting cognitive and affective symptomatology, and they are at a higher risk for Alzheimer's disease. MATERIALS AND METHODS: This study analyzed the neural underpinnings of cognitive and depressive symptoms in a cohort comprising 12 aMCI subjects, 24 late-life MDD patients, and 26 healthy controls (HCs). Participants underwent a detailed neuropsychological assessment and completed a visual attentional oddball task during functional magnetic resonance imaging (fMRI), with evaluations at baseline and at 2-year follow-up. RESULTS: Initial findings showed that aMCI subjects had reduced dACC activation during oddball (target) stimulus detection, a pattern that persisted in longitudinal analyses and correlated with cognitive functioning measures. For HCs, subsequent dACC activation was linked to depression scores. Furthermore, in the affective-cognitive altered groups, later dACC activation correlated with oddball and memory performance. CONCLUSIONS: These findings enhance our comprehension of the neurobiological basis of cognitive and depressive disturbances in aging, indicating that dACC activation in response to a visual attentional oddball task could serve as a neural marker for assessing cognitive impairment and depression in conditions predisposing to Alzheimer's disease.

Being alone after late-life divorce: freedom and loneliness from an intergenerational familial/dyadic perspective.

OBJECTIVES: To examine in-depth experiences of loneliness and freedom after late-life divorce from an intergenerational familial/dyadic perspective in a family-oriented society that also values self-determination. Considering the expansion of late-life divorce, it is important to understand its consequences for the family wellbeing. METHOD: According to phenomenology tradition, data was collected through 51 semi-structured qualitative interviews, comprised from 7 family units (n = 33) including all/most family members and 9 parent-child dyads (n = 18), using thematic-analysis and dyadic interview-analysis principles. Analyzing family units enables a more complex examination of the phenomena, providing a holistic view of family life. RESULTS: Loneliness and freedom experienced simultaneously was the most common. A gap was identified between generations regarding benefits and costs of late-life divorce. Whereas most divorcees emphasized the benefits of freedom, most of their adult-children mainly described the disadvantages of loneliness, perceiving both loneliness and freedom as negative. CONCLUSION: Late-life divorce is a complex experience comprised of both loneliness and freedom. Each generation experiences the benefits and costs of late-life divorce differently. Unique aspects of freedom and loneliness at old age in a socio-cultural context located between self-determination and family-oriented are discussed, including strategies of coping with loneliness. Implications for families and professionals are presented.

Dynamic Features of Body Mass Index in Late Life Predict Cognitive Trajectories and Alzheimer's Disease: A Longitudinal Study.

Background: The causal relationships of late-life body mass index (BMI) with Alzheimer's disease (AD) remains debated. Objective: We aimed to assess the associations of dynamic BMI features (ΔBMIs) with cognitive trajectories, AD biomarkers, and incident AD risk. Methods: We analyzed an 8-year cohort of 542 non-demented individuals who were aged ≥65 years at baseline and had BMI measurements over the first 4 years. ΔBMIs were defined as changing extent (change ≤ or >5%), variability (standard deviation), and trajectories over the first 4 years measured using latent class trajectory modeling. Linear mixed-effect models were utilized to examine the influence of ΔBMIs on changing rates of AD pathology biomarkers, hippocampus volume, and cognitive functions. Cox proportional hazards models were used to test the associations with AD risk. Stratified analyzes were conducted by the baseline BMI group and age. Results: Over the 4-year period, compared to those with stable BMI, individuals who experienced BMI decreases demonstrated accelerated declined memory function (p = 0.006) and amyloid-ß deposition (p = 0.034) while BMI increases were associated with accelerated hippocampal atrophy (p = 0.036). Three BMI dynamic features, including stable BMI, low BMI variability, and persistently high BMI, were associated with lower risk of incident AD (p < 0.005). The associations were validated over the 8-year period after excluding incident AD over the first 4 years. No stratified effects were revealed by the BMI group and age. Conclusions: High and stable BMI in late life could predict better cognitive trajectory and lower risk of AD.

Social Dysfunction and Apathy: Transdiagnostic Domains in Late-Life Cognitive Disorders.

Social dysfunction is a maladaptive process of coping, problem solving, and achieving one's goals. A new definition of apathy was cross-linked to social dysfunction, with a reduced goal-directed behavior and social interaction as a separate dimension. We hypothesized that these two neuropsychiatric symptoms may be included in the mild behavioral impairment diagnostic framework, operationalizing and standardizing late-life neuropsychiatric symptom assessment, to improve risk determination of dementia. Social dysfunction and apathy were transdiagnostic and prodromic for late-life cognitive disorders. A transdiagnostic approach could provide a useful mean for a better understanding of apathy and related conditions such as social behavior.

Predictors of treatment outcome of psychological therapies for common mental health problems (CMHP) in older adults: A systematic literature review.

Identifying factors that impact psychological treatment outcomes in older people with common mental health problems (CMHP) has important implications for supporting healthier and longer lives. The aim of the present study was to synthesise the evidence on predictors of psychological treatment outcomes in older people (aged 65+). PubMed, Scopus, Web of Science and PsycINFO were searched and 3929 articles were identified and screened, with 42 studies (N = 7978, M age = 68.9, SD age = 2.85) included: depression: k = 21, anxiety: k = 11, panic disorder: k = 3, mixed anxiety & depression: k = 3, PTSD: k = 2, various CMHP: k = 2, with CBT being the most common treatment (71%). The review identified 28 factors reported as significant predictors of treatment outcome in at least one study, across different domains: psychosocial (n = 9), clinical (n = 6), treatment-related (n = 6), socio-demographic (n = 4), neurobiological (n = 3). Homework completion was the most consistent predictor of positive treatment outcome. Baseline symptom severity was the most frequently studied significant predictor and across all conditions, with higher baseline symptom severity largely linked to worse treatment outcomes. No significant effects on treatment outcome were reported for gender, income and physical comorbidities. For a large majority of factors evidence was mixed or inconclusive. Further studies are required to identify factors affecting psychological treatment outcomes, which will be important for the development of personalised treatment approaches.

Differential Psychological Treatment Effects in Patients With Late-Life Depression and a History of Childhood Maltreatment.

OBJECTIVE: This is the first interventional study to assess the impact of childhood maltreatment (CM) on psychological treatment outcomes in patients with late-life depression (LLD). METHODS: This is a secondary analysis of a multicenter, randomized controlled trial with 251 participants aged ≥60 years with moderate to severe depression. Participants were randomly assigned to cognitive behavioral therapy for late life depression (LLD-CBT) or to a supportive intervention (SUI). Treatment outcomes were measured by changes in the Geriatric Depression Scale (GDS). RESULTS: In the intention-to-treat sample (n = 229), both LLD-CBT (n = 115) and SUI (n = 114) significantly reduced depressive symptoms in patients with CM, with large effects at post-treatment (d = 0.95 [95% CI: 0.65 to 1.25] in LLD-CBT; d = 0.82 [95% CI: 0.52 to 1.12] in SUI). A significant treatment group*CM interaction (F(1,201.31) = 4.71; p = .031) indicated greater depressive symptom reduction in LLD-CBT compared to SUI at week 5 and post-treatment for patients without CM, but not at 6-month follow-up. Across both treatments, higher severity of the CM subtype 'physical neglect' was associated with a smaller depressive symptom reduction (F(1,207.16) = 5.37; p = .021). CONCLUSIONS: Specific and non-specific psychotherapy effectively reduced depressive symptoms in older individuals with depression and early trauma. For patients without early trauma, LLD-CBT may be preferable over SUI. Considering early trauma subtypes may contribute to develop personalized treatment approaches.

Hippocampal subfield volume in older adults with and without mild cognitive impairment: Effects of worry and cognitive reappraisal.

Studies have confirmed that anxiety, especially worry and rumination, are associated with increased risk for cognitive decline, including Alzheimer's disease and related dementias (ADRD). Hippocampal atrophy is a hallmark of ADRD. We investigated the association between hippocampus and its subfield volumes and late-life global anxiety, worry, and rumination, and emotion regulation strategies. We recruited 110 participants with varying worry severity who underwent magnetic resonance imaging and clinical interviews. We conducted cross-sectional regression analysis between each subfield and anxiety, worry, rumination, reappraisal, and suppression while adjusting for age, sex, race, education, cumulative illness burden, stress, neuroticism, and intracranial volume. We imputed missing data and corrected for multiple comparisons across regions. Greater worry was associated with smaller subiculum volume, whereas greater use of reappraisal was associated with larger subiculum and CA1 volume. Greater worry may be detrimental to the hippocampus and to subfields involved in early ADRD pathology. Use of reappraisal appears protective of hippocampal structure. Worry and reappraisal may be modifiable targets for ADRD prevention.

Relationship between Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores in older adults with major depressive disorder: An analysis of the OPTIMUM clinical trial.

BACKGROUND: The Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS) are commonly used scales to measure depression severity in older adults. METHODS: We utilized data from the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) clinical trial to produce conversion tables relating PHQ-9 and MADRS total scores. We split the sample into training (N = 555) and validation samples (N = 187). Equipercentile linking was performed on the training sample to produce conversion tables for PHQ-9 and MADRS. We compared the original and estimated scores in the validation sample with Bland-Altman analysis. We compared the depression severity level using the original and estimated scores with Chi-square tests. RESULTS: The Bland-Altman analysis confirmed that differences between the original and estimated scores for at least 95 % of the sample fit within 1.96 standard deviations of the mean difference. Chi-square tests showed a significant difference in the proportion of participants at each depression severity category determined using the original and estimated scores. LIMITATIONS: The conversion tables should be used with caution when comparing depression severity at the individual level. CONCLUSIONS: Our conversion tables relating PHQ-9 and MADRS scores can be used to compare treatment outcomes using aggregate data in studies that only used one of these scales.

Cognitive improvement in late-life depression treated with vortioxetine and duloxetine in an eight-week randomized controlled trial: The role of age at first onset and change in depressive symptoms.

BACKGROUND: Age at first onset of depression as a clinical factor affecting cognitive improvement in late life depression was investigated. METHODS: This is a secondary analysis of an eight-week randomized controlled trial involving 452 elderly patients treated by vortioxetine, duloxetine or placebo (1:1:1). Patients were subcategorized into early-onset (LLD-EO) and late-onset (LLD-LO) groups divided by onset age of 50. Cognitive performance was assessed by composite score of Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT) tasks, while depressive symptoms were assessed by Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Vortioxetine and duloxetine exhibited advantages versus placebo in improving cognitive performance in the LLD-LO group, yet not in the LLD-EO group after eight weeks. Patients in the LLD-EO group showed overall advantage to placebo in depressive symptoms before endpoint (week 8) of treatment, while patients in the LLO-LO group showed no advantage until endpoint. Path analysis suggested a direct effect of vortioxetine (B = 0.656, p = .036) and duloxetine (B = 0.726, p = .028) on improving cognition in the LLD-LO group, yet in all-patients treated set both medications improved cognition indirectly through changes of depressive symptoms. LIMITATION: Reliability of clinical history could raise caution as it was collected by subjective recall of patients. CONCLUSION: Age at first onset might affect cognitive improvement as well as change in depressive symptoms and its mediation towards cognitive improvement in late life depression treated with vortioxetine and duloxetine.

Late-life mood disorder as the initial presentation of progressive supranuclear palsy: A case series.

Aim: Progressive supranuclear palsy (PSP) is a rapidly progressive neurodegenerative disorder characterized by Parkinsonism, supranuclear ophthalmoplegia, postural instability, and cognitive impairment. Patients: This case series describes three patients initially diagnosed with late-life mood disorders (depression and bipolar disorder) who were later diagnosed with PSP because of the development of typical neurological symptoms. Result: The diagnostic challenge of PSP is highlighted in this case report, particularly in the early stages, when characteristic symptoms may not be present. The importance of considering PSP in the differential diagnosis of late-life mood disorders, especially in the absence of response to standard antidepressant therapy, is also emphasized. The heterogeneity of PSP is described, with various subtypes and atypical variants presenting with different clinical features. The psychiatric symptoms of PSP include apathy, disinhibition, depression, and anxiety, whereas hallucinations and delusions are less frequent. Tau positron emission tomography imaging is discussed as a potential biomarker for atypical PSP. Conclusion: Early diagnosis and intervention are crucial for improved outcomes in PSP, necessitating further research to enhance the diagnostic and treatment strategies for PSP and other neurodegenerative diseases.

Abnormalities in Electroencephalographic Microstates in Patients with Late-Life Depression.

Background: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear. Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed. Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items. Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.

Diet quality from mid to late life and its association with physical frailty in late life in a cohort of Chinese adults.

BACKGROUND: It is unclear if improving diet quality after midlife could reduce the risk of physical frailty at late life. We aimed to associate changes in diet quality after midlife with physical frailty at late life. METHODS: Diet quality in 12,580 participants from the Singapore Chinese Health Study was assessed with the Dietary Approaches to Stop Hypertension (DASH) scores at baseline (1993-1998; mean age 53 years) and follow-up 3 (2014-2016; mean age 73 years). Physical frailty was assessed using the modified Cardiovascular Health Study phenotype at follow-up 3. Multivariable logistic regressions examined associations between DASH scores and physical frailty. RESULTS: Comparing participants in extreme quartiles of DASH scores, the odds ratios (OR) [95% confidence interval (CI)] for physical frailty were 0.85 (0.73,0.99) at baseline and 0.49 (0.41, 0.58) at follow-up 3. Compared to participants with consistently low DASH scores, participants with consistently high scores (OR 0.74, 95% CI: 0.59, 0.94) and those with > 10% increase in scores (OR 0.78, 95% CI: 0.64, 0.95) had lower odds of frailty. Compared to those in the lowest DASH tertiles at both time-points, significantly lower odds of physical frailty were observed in those who were in the highest DASH tertiles at both time points [0.59 (0.48, 0.73)], and in those who improved their scores from the lowest [0.68 (0.51, 0.91)] or second tertile at baseline [0.61 (0.48, 0.76)] to the highest tertile at follow-up 3. CONCLUSIONS: Maintaining a high diet quality or a substantial improvement in diet quality after midlife could lower the risk of physical frailty at late life.

Age-specific risk factors of depression among the oldest-old - evidence from the multicenter AgeCoDe-AgeQualiDe study.

Purpose: The present study aimed to investigate age-group-specific incidence rates and risk factors for depressive symptoms in the highest age groups. Methods: Data were derived from a prospective multicenter cohort study conducted in primary care - the AgeCoDe/AgeQualiDe study. In total, 2,436 patients 75 years and older were followed from baseline to ninth follow-up. To assess depressive symptoms, the short version of the Geriatric Depression Scale (GDS-15, cutoff score 6) was used. Age-specific competing risk regressions were performed to analyze risk factors for incident depressive symptoms in different age groups (75 to 79, 80 to 84, 85+ years), taking into account the accumulated mortality. Results: The age-specific incidence rate of depression was 33 (95% CI 29-38), 46 (95% CI 40-52) and 63 (95% CI 45-87) per 1,000 person years for the initial age groups 75 to 79, 80 to 84 and 85+ years, respectively. In competing risk regression models, female sex, mobility as well as vision impairment, and subjective cognitive decline (SCD) were found to be risk factors for incident depression for age group 75 to 79, female sex, single/separated marital status, mobility as well as hearing impairment, and SCD for age group 80 to 84, and mobility impairment for age group 85+. Conclusion: Depressive symptoms in latest life are common and the incidence increases with increasing age. Modifiable and differing risk factors across the highest age groups open up the possibility of specifically tailored prevention concepts.