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This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)—parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners. [ABSTRACT FROM AUTHOR]

• Serum citrate concentrations in mild dementia could be associated with subsequent cognitive decline. • In mild dementia APOE- ε4 carriers, serum isocitrate concentrations could be associated with subsequent cognitive decline. • Downregulation of the first half of the TCA cycle with upregulation in the latter half, might be indirectly reflected in serum metabolites' networks. Abnormalities in the Tri-Carboxylic-Acid (TCA) cycle have been documented in dementia. Through network analysis, TCA cycle metabolites could indirectly reflect known dementia-related abnormalities in biochemical pathways, and key metabolites might be associated with prognosis. This study analyzed TCA cycle metabolites as predictors of cognitive decline in a mild dementia cohort and explored potential interactions with the diagnosis of Lewy Body Dementia (LBD) or Alzheimer's Disease (AD) and APOE-ε4 genotype. We included 145 mild dementia patients (LBD = 59; AD = 86). Serum TCA cycle metabolites were analyzed at baseline, and partial correlation networks were conducted. Cognitive performance was measured annually over 5-years with the Mini-mental State Examination. Longitudinal mixed-effects Tobit models evaluated each baseline metabolite as a predictor of 5-years cognitive decline. APOE-ε4 and diagnosis interactions were explored. Results showed comparable metabolite concentrations in LBD and AD. Multiple testing corrected networks showed larger coefficients for a negative correlation between pyruvate – succinate and positive correlations between fumarate – malate and citrate – Isocitrate in both LBD and AD. In the total sample, adjusted mixed models showed significant associations between baseline citrate concentration and longitudinal MMSE scores. In APOE-ε4 carriers, baseline isocitrate predicted MMSE scores. We conclude that, in mild dementia, serum citrate concentrations could be associated with subsequent cognitive decline, as well as isocitrate concentrations in APOE-ε4 carriers. Downregulation of enzymatic activity in the first half of the TCA cycle (decarboxylating dehydrogenases), with upregulation in the latter half (dehydrogenases only), might be indirectly reflected in serum TCA cycle metabolites' networks. [ABSTRACT FROM AUTHOR]

Background and Aims: In older adults with dementia, low body mass index (BMI) is associated with higher mortality and other adverse health outcomes. BMI or nutritional status trajectories from diagnosis have not yet been well described in dementia, especially in people with Lewy body dementia (LBD); a group that has a poorer prognosis. With this study, we aimed to evaluate the BMI trajectory in people diagnosed with mild LBD and Alzheimer's disease (AD). Methods: The Dementia Study of Western Norway is a cohort study with annual assessments. Five‐year measurements of BMI from 196 patients (LBD = 85 and AD = 111) diagnosed with mild dementia were analyzed using adjusted linear mixed‐effects models. Results: There were no differences between LBD and AD in baseline BMI, age, or mini‐mental status examination (MMSE). During the follow‐up, we observed a significant decrease in BMI in the LBD group across the study period (estimation [Est.]: −0.63, SE: 0.14; p < 0.001). By contrast, there was no significant change in BMI trajectory associated with AD diagnosis (Est.: 0.05, SE: 0.15; p = 0.730). Further, the introduction of an interaction term between diagnosis and time in the study showed that this difference (BMI trajectories) was significant (Est.: −0.63, SE: 0.14; p < 0.001). In addition, there was a significant interaction between MMSE total score and the follow‐up time; the lower the MMSE, the lower the BMI (Est.: 0.01, SE: 0.01; p = 0.044). Conclusion: In LBD, BMI significantly decreased with disease progression. In addition, low cognitive performance was associated with a reduction in BMI. These results highlight the importance of BMI evaluation in people with dementia, particularly patients diagnosed with LBD, and suggest that patients with LBD could be targeted for dietary intervention to maintain body weight. [ABSTRACT FROM AUTHOR]

Purpose: The present study aims to explore the association between the quality of life (QoL) score and the clinical and sociodemographic variables in patients with the PSEN1-E280A mutation. We also seek to evaluate the differences between the QoL reported by the patients (P-QoL) and the scores reported by the caregivers (C-QoL). Methods: An analysis of 75 patients with the PSEN1-E280A mutation with mild cognitive impairment and dementia was performed. We used the Quality of Life in Alzheimer Disease (QoL-AD) survey to evaluate QoL as an outcome and evaluated its association with sociodemographic, lifestyle, clinical, and past medical history variables. Results: The largest difference in the median of the QoL-AD score was in those who needed help to eat, those with moderate or severe dementia, those classified as frail or pre-frail, those with moderate social risk, and those with depression. Also, C-QoL was lower than the P-QoL, and the QoL-AD of individuals with severe dementia was lower than for milder forms of the disease. Not needing help to eat, not having a stressful situation in the past 3 months, and the years of education were positively correlated with QoL-AD in the linear model. Conclusion: As studies in similar populations with AD, factors with more impact on QoL are those related to loss of functionality and independence. These factors are also associated with variables related to the current literature with the burden of the disease for the caregivers. [ABSTRACT FROM AUTHOR]

Introduction: The amygdala is implicated in psychiatric illness. Even as the amygdala undergoes significant atrophy in mild dementia, amygdala volume is underexplored as a risk factor for neuropsychiatric symptoms (NPS). Objective: To analyze the association between baseline amygdala volume and the longitudinal trajectories of NPS and cognitive decline in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) over 5 years. Methods: Eighty-nine patients with mild dementia were included (AD = 55; DLB = 34). Amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi-automatic method (Freesurfer 6.0) and normalized by intracranial volumes. The intracranial volume-normalized amygdala was used as a predictor of the Neuropsychiatric Inventory (NPI) total score, ordinal NPI item scores (0 = absence of symptoms, 1–3 = mild symptoms, ≥4 = clinically relevant symptoms), and Mini-Mental State Examination (MMSE) as measured annually over 5 years using gamma, ordinal, and linear mixed-effects models, respectively. The models were adjusted for demographic variables, diagnosis, center of sMRI acquisition, and cognitive performance. Multiple testing-corrected p -values (q -values) are reported. Results: Larger intracranial volume-normalized amygdala was associated with less agitation/aggression (odds ratio (OR) = 0.62 [0.43, 0.90], p = 0.011, q = 0.038) and less MMSE decline per year (fixed effect = 0.70, [0.29, 1.03], p = 0.001, q = 0.010) but more depression (OR = 1.49 [1.09, 2.04], p = 0.013, q = 0.040). Conclusions: Greater amygdala volume in mild dementia is associated with lower odds of developing agitation/aggression, but higher odds of developing depression symptoms during the 5-year study period. [ABSTRACT FROM AUTHOR]

Objectives: We aim to study the effects of the prescription of benzodiazepines and antidepressants on cognitive and functional decline in older adults living with Alzheimer's disease (AD) and Lewy body dementia (LBD) over a 5‐year follow‐up. Methods: This is a longitudinal analysis of a Norwegian cohort study entitled "The Dementia Study of Western Norway" (DemVest). We included 196 patients newly diagnosed with AD (n = 111) and LBD (n = 85), followed annually for 5 years. Three prescription groups were defined: only benzodiazepines (BZD), only antidepressants (ADep), and the combination of benzodiazepines and antidepressants (BZD‐ADep). Linear mixed‐effects models were conducted to analyze the effect of the defined groups on the outcomes. The outcomes were functional decline, measured by the Rapid Disability Rating Scale—2, and cognition measured with the Mini‐Mental State Examination. Results: Prescription of the combination of benzodiazepines and antidepressants in LBD was associated with faster functional decline. In AD, the prescription of BZD and BZD‐ADep was associated with greater functional deterioration. ADep alone did not show positive or negative significant associations with the studied outcomes. Conclusions: BZD and especially the combination of BZD and ADep are associated with functional decline in AD and LBD and should be used cautiously. Key Points: Combination of benzodiazepines and antidepressants in Lewy body dementia was associated with faster functional declineBenzodiazepines and the combination of benzodiazepines and antidepressants in Alzheimer's disease were associated with greater functional deteriorationThe consumption of antidepressants alone did not show positive or negative significant associations with cognitive or functional decline [ABSTRACT FROM AUTHOR]

Background: In dementia, functional status depends on multiple factors in addition to cognition. Nutritional status is a potentially modifiable factor related to homeostasis and proper functioning of body systems and may contribute to cognitive and functional decline.Objective: This paper aims to analyze the association of malnutrition with the course of cognitive and functional decline in people living with dementia.Methods: This is an analysis of a longitudinal cohort study, the Dementia Study of Western Norway. Data of 202 patients diagnosed with mild dementia were analyzed; Alzheimer's disease (AD) (n = 103), Lewy body dementia (LBD) (n = 74), and other dementias (OD) (n = 25). Cognition was assessed with the Mini-Mental State Examination and functional decline through the activities of daily living included in the Rapid Disability Rating Scale. The Global Leadership Initiative on Malnutrition Index was used to determine nutritional status. Associations of nutritional status with cognitive and functional decline were evaluated through adjusted linear mixed models.Results: At baseline, the prevalence of general malnutrition was 28.7%; 17.3% were classified as moderate malnutrition and 11.38% as severe malnutrition (there were no significant differences between AD and LBD). Malnutrition at diagnosis and over follow-up was a significant predictor of functional-decline, but not of cognitive decline.Conclusion: According to our results malnutrition was associated with faster functional loss but, not cognitive decline in older adults with dementia. A more comprehensive dementia approach including nutritional assessments could improve prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Frailty is recognized as a clinical condition associated with increased vulnerability for developing negative health outcomes but has been little studied in patients with Parkinson's disease (PD). Here, we investigated the risk of frailty in de novo PD patients and its association with subsequent development of dementia.Methods: We conducted a three-year longitudinal population-based study of 192 drug-naive newly diagnosed PD patients and 172 controls (No-PD) matched for age, sex, and education. Frailty was measured using the frailty index (FI). Logistic regression models, adjusting for potential confounders, were conducted to assess the association between frailty at the time of PD diagnosis and the subsequent odds for developing PD dementia during follow-up.Results: The mean baseline FI score was higher in the PD (0.21 ± 0.10) than in the No-PD group (0.11 ± 0.07, p < 0.001). One-third of PD patients had high-FI (>0,25), compared to 5% in the no-PD group. Participants with PD had an increased risk to present frailty with an odds ratio (OR) of 6.68 (SE 2.70 IC 95% [3.15; 15.62], p-value <0.001) compared to the No-PD group. PD Participants with greater FI measured at baseline had increased odds of having dementia within three years of follow-up, after adjustment for age and sex (OR 2.91 SE 1.00 IC 95% [1.54; 5.99] p-value = 0.002).Conclusion: Frailty is common in people with newly diagnosed PD and associated with increased odds for subsequent development of dementia in a three-year follow-up. This study emphasizes the prognostic importance of frailty in PD from the earliest clinical stages. [ABSTRACT FROM AUTHOR]