A Systematic Review of Antidepressants and Psychotherapy Commonly Used in the Treatment of Late Life Depression for Their Effects on Cognition.

Cognitive dysfunction is common in late life depression (LLD) and is a major risk factor for dementia. Recent studies show limited improvement in cognition with commonly employed treatments for LLD, contradicting the notion that cognition "returns to normal" with treatment. However, findings differ with the treatments used. The aim of this study is to perform a systematic review of studies of antidepressants and psychotherapies commonly employed in LLD to determine their effects on cognition, particularly processing speed, memory, and executive function. We searched for trials of acute phase treatment, in nondemented individuals 60 years and older with unipolar nonpsychotic Major Depressive Disorder, that assessed cognitive performance with neuropsychological tests before and after treatment. We compared the magnitude of change in cognition by examining within group effect sizes. Six antidepressant trials and two psychotherapy trials (both using Problem Solving Therapy)(PST) provided relatively comparable data that allowed for quantitative comparison. Nine other antidepressant trials provided descriptive findings. Sertraline and vortioxetine had significant positive effects on processing speed and memory. Duloxetine had significant effects on memory. The most selective SRIs-citalopram and escitalopram-had minimal effects on cognition and citalopram had adverse effects in depression nonresponders. PST had modest effects on processing speed and no effect on memory. Effects of practice and improvement in depression on cognition are examined. In all but one study, cognition was a secondary outcome and various quality indicators (e.g. blinding cognitive assessment to treatment) were often not reported. As a consequence, these findings must be considered preliminary.

Flavonoid-Rich Fruit Intake in Midlife and Late-Life and Associations with Risk of Dementia: The Framingham Heart Study.

BACKGROUND: Fruits are an important source of flavonoids, and greater intake of dietary flavonoids in older adults has been shown to be associated with decreased risk of dementia. It is unclear whether this relationship is similar or different between younger adults and older adults. OBJECTIVES: We examined for associations between midlife and late-life intake of flavonoid-rich fruits and incident dementia. We hypothesized that greater total cumulative intake of flavonoid-rich fruits in midlife and late-life adults would be associated with reduced risk of all-cause dementia. DESIGN: Longitudinal, cohort study design. SETTING: Framingham Heart Study, which is a longitudinal, multi-generational community-based cohort based in Framingham, Massachusetts, USA. PARTICIPANTS: Participants from the Framingham Heart Study Offspring cohort were included (n = 2,790) who attended the fifth core exam between 1991 to 1995, and were dementia-free and at least 45 years of age at that time, as well as had valid food frequency questionnaires from the fifth to ninth core exams. MEASUREMENTS: Consumption of fruits with high flavonoid content or are important contributors to overall flavonoid intake was collected via food frequency questionnaire. Flavonoid-rich fruits from the food frequency questionnaire included raisins or grapes, prunes, bananas, fresh apples or pears, apple juice or cider, oranges, orange juice, grapefruit, grapefruit juice, strawberries, blueberries, and peaches, apricots, or plums. Dementia ascertainment was based on a multidisciplinary consensus committee, and included all-cause dementia and Alzheimer's disease dementia diagnoses based on research criteria. Cox models were used to examine associations between cumulative fruit intake and incident dementia, stratified by midlife (45-59 years; n = 1,642) and late-life (60-82 years; n = 1,148). RESULTS: Greater cumulative total fruit intake in midlife, but not late-life, was significantly associated with a 44% decreased risk of all-cause dementia (HR = 0.56; 95% CI = 0.32 - 0.98; p = 0.044). Decreased risk of all-cause dementia was also associated with higher intake of apples or pears in midlife and late-life, as well as higher intake of raisins or grapes in midlife only, and higher intake of oranges, grapefruit, blueberries, and peaches, apricots, or plums in late-life only. CONCLUSIONS: Among participants from the Framingham Heart Study, greater overall consumption of flavonoid-rich fruits in midlife was associated with reduced risk of dementia, though intake of specific fruits in midlife and late-life may have a protective role against developing dementia. These findings may help to inform future recommendations on when dietary interventions may be most beneficial to healthy brain aging across the life course.

Older and Better: A Narrative Review of Successful Aging and Adaptation to Pain in Late Life.

"Invariably, the self-assessed QoL was far better than I, as a physician, would have anticipated from the diseases and disabilities that you reported." -Ben Eiseman, MD, based on a survey of his octogenarian Yale University classmates. BACKGROUND: Chronic pain control is a high priority for the elderly; it is one of the most frequently encountered medical problems in this group. Chronic pain affects 60%-75% of people aged 65 years and older. Chronic pain's prevalence is even higher in those living in assisted living or nursing homes. Based on epidemiological data, the prevalence of chronic pain is directly proportional to age and is especially so in women. At least one in 3 patients over age 65 report significant ongoing pain that is often inadequately treated. Despite this high prevalence of chronic pain in older persons, aging research sheds light on how this suffering may be reduced. Healthy aging is not an oxymoron. Successful aging and adaptation to chronic pain involve similar medical, temperamental, behavioral, and cultural factors. Older patients with chronic pain face well-documented cultural bias, fear, and clinical pessimism; but adaptive coping is a realistic expectation. OBJECTIVES: This narrative review aims to summarize the available literature on strategies used by older persons to optimize adaptation to late-life pain. STUDY DESIGN: This is a narrative review of a PubMed literature search 1947 to March 4, 2024. METHODS: A PubMed literature search covering years 1947 to March 4, 2024 was performed using permutations of the search terms pain, chronic pain, persistent pain, aging, elderly, and coping. Relevant articles were also obtained from careful review of the references in articles identified in the search. RESULTS: I summarized the available literature on strategies used by older persons to optimize adaptation to late-life pain. There are distinct differences between older persons and younger persons in the strategies they use to cope with chronic pain. Furthermore, I identified significant overlap between strategies and actions used by older persons to cope with pain and those strategies and actions used to successfully adapt to the aging process; these commonalities demonstrate a linkage of these adjustment processes and have clinical utility. Also presented are 2 cases that demonstrate the relevance of these factors for treating elderly patients with chronic pain. LIMITATIONS: The literature search was limited to PubMed, which excluded psychology databases. CONCLUSIONS: Chronic pain is common in the elderly and is not adequately treated. Data indicate that older persons can benefit from guidance toward distinct attitudes and actions they can employ to cope with persistent pain. Epidemiologic and aging literature describe attitudes and behaviors that facilitate health and wellbeing during aging. Data from gerontology and from research on chronic pain in elderly patients converge upon factors that are common to better adaptation to both aging and late-life pain. I describe these common factors, which I categorize as treatment-factors, traits, attitudes, and actions. Two cases are presented to demonstrate these concepts.

Chemosensory anhedonia facilitates depressive symptoms and cognitive impairment in late-life depression.

AIM: Chemosensory anhedonia refers to the lack of hedonic ability to experience pleasure through the senses of smell and taste, which reduces the pleasure and comfort of food, and increases the risk of nutritional and immune deficiencies. However, there is no direct scientific evidence regarding chemosensory anhedonia in patients with late-life depression (LLD). The aim of this study was to investigate chemosensory anhedonia in patients with LLD, and its potential association with depressive symptoms and cognitive function. METHODS: A total of 114 patients with LLD and 92 normal controls were included in this study. They experienced clinical assessment, Chemosensory Pleasure Scale assessment, 17-item Hamilton Depression Rating Scale assessment and cognitive assessments, which contain the Verbal Fluency Test. The associations between chemosensory pleasure and depressive symptoms or cognitive function in patients with LLD were explored using partial correlation analysis and mediation analysis. RESULTS: The Chemosensory Pleasure Scale scores were lower in the LLD group than in the normal control group, and were negatively correlated with the total scores and factors' scores (retardation, cognitive bias and anxiety/somatization) of the 17-item Hamilton Depression Rating Scale, and positively correlated with the Verbal Fluency Test scores. The scores for the Food and Imagination dimensions of the Chemosensory Pleasure Scale showed partial mediating effects on the differences in Cognitive bias (a factor of the 17-item Hamilton Depression Rating Scale) between patients with LLD and normal controls. CONCLUSIONS: Patients with LLD showed significant chemosensory anhedonia, and both depressive symptoms and cognitive impairment were associated with the severity of chemosensory anhedonia. Enhancing chemosensory pleasure in patients with LLD could potentially ameliorate their depressive symptoms. Geriatr Gerontol Int 2024; 24: 1022-1029.

Gerotranscendence as a Life Perspective Among Nursing Home Residents: A Qualitative Study Into Positive Ageing While Dependent on 24/7 Care.

AIMS: To examine whether and how older nursing home residents recognise characteristics of gerotranscendence, and to contribute to a critical and comprehensive view of gerotranscendence in this particular group. BACKGROUND: Gerotranscendence is a psychosocial, spiritual development theory within the field of positive ageing that represents: a shift in meta-perspective, from a materialistic and rational vision to a cosmic and transcendent life perspective, followed by an increase in life satisfaction. DESIGN: A qualitative study using a narrative hermeneutical approach. METHODS: Participants were 20 residents of a nursing home in the Netherlands, aged 77 to 105 (mean age: 90). The semi-structured interviews, conducted in April 2023, were based on Tornstam's 10-item Gerotranscendence Scale. Special attention was paid to the technique of interviewing these frail, older adults, some of them diagnosed with dementia. FINDINGS: All respondents recognised several characteristics of gerotranscendence, or signs of it emerged from the research data. There is a larger middle group with respondents who call themselves 'down-to-earth'. They mainly recognise the relational characteristics. Another group appears to be more contemplative and shows more affinity with the abstract, cosmic characteristics. They have developed a gerotranscendent wisdom: there is insight, contextualism and relativism, peace of mind, room for life's paradoxes, a high degree of (self-)acceptance and an ability to 'let go'. The data show considerable heterogeneity in thoughts, perspectives and degrees of gerotranscendence. DISCUSSION: Respondents found some questions difficult to answer, resulting in a critical assessment of how to understand the responses given. This puts pressure on data quality for this current study and for critical gerotranscendence research in general. Furthermore, interviewing older nursing home residents requires a custom setting and possibly a new interview methodology. REPORTING METHOD: This report adheres to the standards for reporting qualitative research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Brain age is not a significant predictor of relapse risk in late-life depression.

INTRODUCTION: Late-life depression (LLD) has been associated cross-sectionally with lower brain structural volumes and accelerated brain aging compared to healthy controls (HC). There are few longitudinal studies on the neurobiological predictors of recurrence in LLD. We tested a machine learning (ML) brain age model and its prospective association with LLD recurrence risk. METHODS: We recruited individuals with LLD (n=102) and HC (n=43) into a multi-site 2-yr longitudinal study. Individuals with LLD were enrolled within 4 months of remission. Remitted LLD participants underwent baseline neuroimaging and longitudinal clinical follow-up. Over 2 years, 43 LLD participants relapsed (REL) and 59 stayed in remission (REM). We used a previously developed ML brain age algorithm to compute brain age at baseline and we evaluated brain age group differences (HC vs. LLD and HC vs. REM vs. REL). We conducted a Cox proportional hazards model to evaluate whether baseline brain age predicted time to relapse. RESULTS: We found that brain age did not significantly differ between HC and LLD as well as HC, REM, and REL groups. Brain age did not significantly predict time to relapse. DISCUSSION: In contrast to our hypothesis, we found that brain age did not differ between non-depressed controls and individuals with remitted LLD, and brain age was not associated with subsequent recurrence. This is in contrast to existing literature which has identified baseline brain age differences in late life but in line with work that shows no differences between those who do and do not relapse on gross structural measures.

The N-3 polyunsaturated fatty acids supplementation to prevent depression recurrence in patients with late-life depression: A 52-week double-blind, placebo-controlled trial.

BACKGROUND: Reports on the efficacy of omega-3 fatty acids (n-3 PUFAs) for the treatment of late-life depression (LLD) are mixed, and most studies focus on the modification of depressive symptoms rather than depression prevention. The aim of the present study was to investigate the efficacy of n-3 PUFAs in preventing depressive recurrence in patients with late-life depression. In addition, we investigated the effects of n-3 PUFAs on changes in depressive and anxiety symptoms and inflammatory markers in LLD. METHODS: A 52-week, double-blind, randomized, controlled trial was conducted. We enrolled a total of 39 euthymic patients with LLD. They were randomized to receive either n-3 PUFAs (1.2 g per day of eicosapentaenoic acid and 1 g of docosahexaenoic acid) or placebo for 52 weeks. Recurrence of depression and severity of depression symptoms were assessed at baseline and weeks 4, 8, 16, 24, 32, 40, and 52. RESULTS: A total of 39 patients completed the trial with 19 in the n-3 PUFAs group and 20 in the placebo group. Cox proportional hazard regression indicated that n-3 PUFAs had significant protective effect on depression recurrence (Hazard Ratio: 0.295, 95 % Confidence Interval: 0.093-0.931, p value =0.037). But n-3 PUFAs intervention had no significant effect in reducing depressive or anxiety symptoms, inflammatory markers over the placebo group. LIMITATION: The results should be interpreted with consideration of the modest sample size. CONCLUSION: These findings suggest that n-3 PUFAs may have a prophylactic effect in currently euthymic patients with LLD.

Assessing the efficacy and safety of combined buspirone and venlafaxine treatment in late-life depression accompanied by cognitive impairment: A randomized controlled trial.

BACKGROUND: Late-life depression, often accompanied by cognitive impairment, poses significant clinical challenges owing to its complex etiology and diverse manifestations. While antidepressants like venlafaxine and anxiolytics such as buspirone are effective for treating depression, their effects on cognitive function remain less well-understood. With the aging population increasingly experiencing geriatric depression, there is an urgent need for innovative treatment approaches that address both depressive symptoms and cognitive impairments. OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of combined buspirone and venlafaxine therapy in elderly patients diagnosed with geriatric depression accompanied by cognitive impairment. METHODS: A 12-week, randomized controlled trial was conducted involving 170 elderly patients. Participants were randomized into two groups: one receiving venlafaxine alone (control group) and the other receiving a combination of venlafaxine and buspirone (experimental group). The primary analysis was performed using an Intent-to-Treat (ITT) approach with mixed-effects linear models to assess changes in depressive symptoms, cognitive function, and anxiety levels. A supplementary Per-Protocol (PP) analysis, utilizing repeated measures ANOVA, was also conducted. RESULTS: The ITT analysis showed that the combination therapy significantly reduced depressive symptoms, as indicated by the HAMD-17 scores (p = 0.033 at week 12). Cognitive function, as measured by MoCA scores, also improved significantly in the experimental group by week 12 (p = 0.025). However, no statistically significant differences were observed in anxiety reduction between the groups (p = 0.127). The PP analysis confirmed these findings, demonstrating consistent improvements in depressive symptoms and cognitive function, particularly in those who completed the full course of treatment. The incidence of adverse events was comparable between groups, primarily mild and manageable symptoms like dry mouth, dizziness, and fatigue. CONCLUSION: The combination of buspirone and venlafaxine was found to be effective in reducing depressive symptoms and enhancing cognitive function in elderly patients with geriatric depression. However, the long-term benefits, especially regarding anxiety reduction, require further investigation. Future studies should consider larger sample sizes, longer follow-up periods, and the inclusion of placebo controls to fully assess the efficacy and safety of this treatment approach.

Anxiety in late-life depression is associated with poorer performance across multiple cognitive domains.

OBJECTIVE: Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains. METHOD: Older adults with major depressive disorder (N = 228, ages 65-91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning. RESULTS: Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity. CONCLUSIONS: Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.

Odor identification dysfunction in late-life depression with suicidal ideation.

BACKGROUND: Suicide is more prevalent among older adults compared to younger individuals. Late-life depression (LLD) poses the highest risk for suicide. However, early recognition of suicidal ideation is challenging. Dysfunction in odor identification (OI), a characteristic of LLD, may hold potential for early identification of suicidal ideation. This study aims to compare OI between LLD patients with suicidal ideation (LLD-S) and LLD patients without suicidal ideation (LLD-NS), and examine its relationship with cognitive function. METHODS: A total of 262 LLD-NS patients, 63 LLD-S patients, and 316 healthy normal older adults (HOAs) underwent OI testing, standardized clinical interviews, and comprehensive neuropsychological assessments. RESULTS: (1) LLD-S patients exhibited lower OI scores and poorer cognitive performance (including global cognition, information processing speed, memory, language, executive function, and visuospatial ability) compared to LLD-NS patients and HOAs. (2) There were interactive effects between suicidal ideation and OI dysfunction, leading to lower scores in information processing speed and visuospatial ability. (3) OI dysfunction mediated the differences in cognition between the LLD-NS and LLD-S groups. LIMITATIONS: The present study was a cross-sectional design. CONCLUSIONS: LLD-S patients had worse odor identification than LLD-NS patients and HOAs, suggesting that OI testing could be a valuable approach for identifying suicidal ideation in LLD and screening for suicide risk. The presence of both OI impairment and suicidal ideation was associated with poorer cognitive performance in LLD.

The Care of Older People With Depression in Nigeria: Qualitative Exploration of the Experience of Lay Providers in Primary Care Settings.

OBJECTIVES: There is a large treatment gap for mental health conditions in sub-Saharan Africa where most patients who receive any care do so from lay primary health care workers (PHCW). We sought to examine the experiences of PHCW who provide care for older people with depression in Nigerian primary health care (PHC) settings. METHODS: Qualitative study design. A total of 24 PHCW participated. Using in-depth key informant interviews (KIIs), we explored the views of 15 PHCW selected from 10 rural and urban PHCs in South-Western Nigeria. An additional focus group discussion comprising nine participants was also conducted to discuss emerging themes from KIIs. Data were analysed using thematic analysis. RESULTS: Three overall themes were identified: views about depression, treatment options, and community outreach implications. Participants perceived depression in older people as being characterised by a range of mood, behavioural, and cognitive symptoms which made clinical assessments particularly challenging. Common treatment options used by PHCW included general advice and counselling, as well as frequent need to prescribe mild analgesics, vitamins and occasional sedatives in line with patients' expectations. Antidepressants were rarely used even though PHCW are authorised. While home visits are part of their expected work schedule, PHCW rarely implemented these due to non-availability of transport facilities. Mobile technology was identified as a possible way of overcoming this constraint to providing community based mental healthcare for older people. CONCLUSION: PHCWs perceived that patients' poor cognitive performance, expectations to prescribe sedatives, analgesics and vitamins, as well as non-existence of community-based services were existing barriers to providing evidenced based continued care for older people with depression in the study settings.

A qualitative study on general practitioners' perspectives on late-life depression in Singapore-part I: patient presentations and behaviours.

Background: Detection and management of late-life depression largely relies on primary care. Yet in Singapore, older adults are unlikely to seek help for their mental health from their primary care providers. This qualitative descriptive study explores how late-life depression manifests to general practitioners (GPs) in the Singaporean primary care setting. Methods: Twenty-eight private GPs practicing in Singapore were asked about their clinical experience with late-life depression during semi-structured group and individual discussions conducted online. Participants were purposively sampled across age, gender, and ethnicity (Chinese, Malay, Indian). Transcripts were analysed with reflexive thematic analysis. Findings: To GPs, depression in older patients often manifests through somatic symptoms or subtle behavioural changes, only detectable through follow-ups or collateral history. GPs reported that older patients attribute depressive symptoms to normal ageing or do not mention them, particularly within an Asian culture encouraging stoic endurance. GPs perceived late-life depression as reactions to ageing-related stressors, with male, low-income, or institutionalised patients being at particular risk of insidious, severe depression. GPs noted ethnic differences regarding families' involvement in care, which they described as helpful, but sometimes stress-provoking for patients. Fear of burdensomeness or loss of autonomy/social role could prompt rejection of diagnosis and treatment in patients. GPs considered good patient-doctor rapport as a facilitator at every step of the care process, noting more favourable prognosis in care-concordant patients. Interpretation: Depression in older adults in Singapore can be covert, with favourable outcomes relying on GPs' ability to pick up on subtle changes, assess patients holistically, and build rapport with patients and families. Funding: This work was funded by the Division of Family Medicine Research Capabilities Building Budget under the project "Technology and Compassion: Improving Patient Outcomes Through Data Analytics and Patients' Voice in Primary Care" [NUHSRO/2022/049/NUSMed/DFM].

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.

Childhood socio-economic disadvantages versus adverse care experiences: Mediation and moderation impacts on late-life depressive symptoms.

BACKGROUND: Whether material deprivation-related childhood socio-economic disadvantages (CSD) and care-related adverse childhood experiences (ACE) have different impacts on depressive symptoms in middle-aged and older people is unclear. METHODS: In the Guangzhou Biobank Cohort Study, CSD and ACE were assessed by 7 and 5 culturally sensitive questions, respectively, on 8,716 participants aged 50+. Depressive symptoms were measured by 15-item Geriatric Depression Scale (GDS). Multivariable linear regression, stratification analyses, and mediation analyses were done. RESULTS: Higher CSD and ACE scores were associated with higher GDS score in dose-response manner (P for trend <0.001). Participants with one point increment in CSD and ACE had higher GDS score by 0.11 (95% confidence interval [CI], 0.09-0.14) and 0.41 (95% CI, 0.35-0.47), respectively. The association of CSD with GDS score was significant in women only (P for sex interaction <0.001; women: ß (95% CI)=0.14 (0.11-0.17), men: 0.04 (-0.01 to 0.08)). The association between ACE and GDS score was stronger in participants with high social deprivation index (SDI) (P for interaction = 0.01; low SDI: ß (95% CI)=0.36 (0.29-0.43), high SDI: 0.64 (0.48-0.80)). The proportion of association of CSD and ACE scores with GDS score mediated via education was 20.11% and 2.28%. CONCLUSIONS: CSD and ACE were associated with late-life depressive symptoms with dose-response patterns, especially in women and those with low adulthood socio-economic status. Education was a major mediator for CSD but not ACE. Eliminating ACE should be a top priority.

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.

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.

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.

Choice intention for the national volume-based procurement drug and its associated factors: a cross-sectional study on patients with late-life depression in China.

BACKGROUND: The national volume-based procurement (NVBP) policy has significantly decreased prices and increased the accessibility of NVBP drugs. Nevertheless, issues such as heightened adverse reactions and suboptimal efficacy have arisen. Concerns regarding the quality of low-cost medications and the absence of long-term research have been widely recognized. This has led to caution among patients with late-life depression (LLD) due to their delicate health and the severity of their condition. This study evaluated the choice intention for NVBP drugs and associated factors in older patients with LLD. METHODS: A weighted sample of 408 participants between December 2022 and March 2023 were included. Data were collected via face-to-face interviews and questionnaires. To identify significant associated factors of choice intention, a multilevel logistic regression model was employed. RESULTS: Over half (53.68%) of older patients with LLD intended to choose NVBP drugs. Associated factors included self-assessed poor economy, higher out-of-pocket expenses, monthly household income exceeding CNY 6000, absence of other non-communicable chronic diseases, ordinary registration, urban employee medical insurance, no requirements for brand-name drugs, adverse reactions after using NVBP drugs, and rejection of physicians' recommendation for NVBP drugs. The interaction effect between the real economic condition and patients self-assessed economy significantly influences choice intention for NVBP drugs. Among 124 patients with self-assessed poor economy, 75 showed a higher intention to use NVBP drugs. In these patients, age, medical insurance reimbursement, and brand awareness were significantly associated with choice intention. CONCLUSION: Economic factors, physical conditions, medical needs, and physician recommendations significantly influenced the choice intention for NVBP drugs. The choice intention can be improved by strengthening physician-patient communication, increasing the scope and proportion of medical insurance reimbursement, improving substitution studies, and conducting post-marketing re-evaluations of NVBP drugs.

Late-Life Blood Pressure and Cerebral Amyloid Angiopathy: Findings from the U.S. National Alzheimer's Coordinating Center Uniform Dataset.

High blood pressure (BP) and cerebral amyloid angiopathy (CAA) are two common risk factors for intracranial hemorrhage, potentially leading to cognitive impairment. Less is known about the relationship between BP and CAA, the examination of which was the objective of this study. We analyzed data from 2510 participants in the National Alzheimer's Coordinating Center (NACC) who had information on longitudinal BP measurements before death and on CAA from autopsy. Using the average of four systolic BPs (SBPs) prior to death, SBP was categorized into three groups: <120 mmHg (n = 435), 120-139 mmHg (n = 1335), and ≥140 mmHg (n = 740). CAA was diagnosed using immunohistochemistry in 1580 participants and categorized as mild (n = 759), moderate (n = 529), or severe (n = 292). When adjusted for age at death, sex, APOE genotype, Braak, CERAD, antihypertensive medication use, and microinfarcts, the odds ratios (95% CIs) for CAA associated with SBPs of 120-139 and ≥140 mmHg were 0.91 (0.74-1.12) and 1.00 (0.80-1.26), respectively. Findings from predictor effect plots show no variation in the probability of CAA between the three SBP categories. Microbleeds had no association with CAA, but among those with SBP ≥ 130 mmHg, the proportion of those with microbleeds was numerically greater in those with more severe CAA (p for trend, 0.084). In conclusion, we found no evidence of an association between SBP and CAA. Future studies need to develop non-invasive laboratory tests to diagnose CAA and prospectively examine this association and its implication on the pathophysiology and outcome of Alzheimer's disease.

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.