BackgroundAmong neuropsychiatric symptoms (NPSs) of Alzheimer's disease (AD), agitation has been shown to occur commonly in the course of AD, overlapping or comorbid with other NPSs.ObjectiveThe proportion of patients with agitation and the severity of agitation appear to differ depending on the neurocognitive stage of AD, and knowledge about the characteristic comorbid symptom pattern may help in elucidation of the underlying mechanism.MethodsAmong 421 clinic-based patients with AD, we re-analyzed the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) to examine the correlations between the scores for agitation and those for other Neuropsychiatric Inventory subscales in each neurocognitive stage of AD (mild, moderate, and severe) classified according to scores in Mini-Mental State Examination.ResultsThe scores for agitation were positively and robustly correlated with the scores for irritability in all stages of AD, and with the scores for anxiety in the moderate and severe stages. The scores for agitation were also correlated with those for sleep disorders in severe AD stage or disinhibition in the moderate AD stage. Multiple regression analysis identified irritability influencing the agitation in moderate and severe stages, and sleep disorders influencing the agitation in the severe stage.ConclusionsAs comorbid NPSs with agitation, characteristic affective, impulsive, and circadian abnormalities may be relevant to generate diverse subsyndromes in AD. Irritability consistently causes agitated behaviors, including refusal to take one's own care, and diurnal rhythm disorder in the severe AD stage may also cause poor acceptance for self-care.

Agitation is a common and difficult-to-manage neuropsychiatric syndrome in dementia. Recently, an association with the autonomous nervous system has been suggested. From the literature researched, however, only two studies investigating autonomic function concomitant to agitation situations appeared; one case series comprised two American veterans with vascular and Alzheimer's dementia, respectively, and in a case series of patients with CLN3 (juvenile neuronal ceroid lipofuscinosis), this was found to be the most common neurodegenerative disease leading to dementia in childhood. In both case series, the measurement of the autonomic system disclosed a parasympathetic withdrawal and sympathetic hyperactivity in the temporal context with agitated behavior. If the time-wise-related autonomic imbalance shown previously can be demonstrated in a larger cohort of patients with Alzheimer's disease, the use of transcutaneous vagal stimulation might be a potential paradigm shift in the treatment of agitation in Alzheimer's disease.

Intracellular alpha-synuclein aggregates, known as Lewy bodies (LB), are commonly observed in Alzheimer's disease (AD) dementia. Post-mortem studies have shown a higher frequency of neuropsychiatric symptoms among individuals with AD and LB co-pathology. However, the effects of in vivo-measured LB pathology on neuropsychiatric symptoms in AD remain underexplored. This study aimed to evaluate cross-sectional and longitudinal effects of in vivo-measured LB pathology on neuropsychiatric symptoms across the AD continuum. We analyzed data from 1,169 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants had in vivo measures of LB pathology (assessed using an alpha-synuclein seed amplification assay), amyloid-beta (Aβ) and phosphorylated tau (p-tau) levels in cerebrospinal fluid (CSF), and neuropsychiatric symptoms evaluated using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Logistic and Cox proportional hazards regression models were used to assess cross-sectional and longitudinal effects, respectively, adjusting for age, sex, and cognitive status. Participants had a mean baseline age of 73.05 (SD 7.22) years, 47.13% were women, 426 (36.44%) cognitively unimpaired, and 743 (63.56%) cognitively impaired. In cross-sectional analyses, LB pathology was associated with higher rates of anxiety, apathy, motor disturbances, and appetite disturbances. In longitudinal analyses, LB pathology increased the risk of developing psychosis and anxiety. These effects were independent of Aβ and p-tau. Our results suggest that in vivo-measured LB pathology is closely associated with neuropsychiatric symptoms across the AD continuum. These findings underscore the potential of in vivo LB detection as a marker for identifying individuals at increased risk of neuropsychiatric symptoms, both in clinical trials and in clinical practice.

Neuropsychiatric symptoms (NPS) are considered diagnostic and prognostic indicators of dementia and are attributable to neurodegenerative processes. Little is known about the prognostic value of early NPS on executive functioning (EF) decline in Alzheimer's disease and related dementias (ADRD). We examined whether baseline NPS predicted the rate of executive function (EF) decline among older adults with ADRD.

Older adults (n = 1625) with cognitive impairment were selected from the National Alzheimer's Coordinating Center database. EF was estimated with a latent factor indicated by scores on Number Span Backward, Letter Fluency, and Trail Making-Part B. A curve of factors (CUFF) latent growth curve model was estimated to examine rate of change over four years. Baseline NPS severity was entered as a predictor in the model to examine its influence on the rate of change in EF over time.

The CUFF models exhibited good fit. EF significantly declined over four waves (slope = -.16, p < .001). Initial visit NPS severity predicted decline in EF (slope = .013, p < .001), such that those with greater baseline NPS severity demonstrated a more rapid decline in EF performance over time. Presence of 2 NPS significantly predicted EF decline, and those with medium total NPS severity (NPS score of 2-4) at baseline exhibited a sharper decline in EF.

Findings underscore the importance of targeting NPS early across ADRD syndromes to minimize EF decline, offering novel insights into how early NPS treatment may alter cognitive trajectories. We provide an innovative, user-friendly web-based application that may be helpful for personalized treatment planning.

Behavioral and psychological symptoms of dementia (BPSD) are a common driver of suffering and high care needs. We describe the Swedish BPSD registry, founded in 2010 to develop an evidence base for quality improvement in the care of patients with BPSD. Further, we illustrate the potential of the registry by evaluating how individual BPSD affects mortality.

The registry provides a framework for documenting the occurrence of BPSD, formulating individual care plans, and following up outcomes. Symptoms are recorded by the nursing home version of the neuropsychiatric inventory (NPI), and data are entered by trained staff, mainly at institutional care facilities.

Enrollment in the registry totaled 114,869 patients with dementia and a mean age of 84 years. Patients were followed until death (median overall survival 2.2 years) or loss to follow-up (median time under observation 4.2 years in patients remaining alive). Common symptoms included agitation/aggression, aberrant motor behavior, and irritability. Mortality increased with NPI severity and use of neuroleptics but decreased in patients receiving cholinesterase inhibitors or memantine.

The scale, completeness, and duration of the registry, together with the possibility of linking to other data sources, offer great potential for data-driven research.

The Swedish BPSD Registry, founded in 2010, has followed over 114,000 patients collecting data on symptoms, care plans, interventions and outcomes.The registry provides a framework for providing and evaluating person-centered care for patients with BPSD, and represents an unparalleled data source for research into BPSD and its management.Mortality increased in patients with more severe BPSD symptoms and for those treated with neuroleptics, but decreased in patients receiving cholinesterase inhibitors or mematine.

In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum. Participants were assigned a Braak stage at baseline and followed for 1.97 (s.d. 0.62) years. NPS were investigated using the Mild Behavioral Impairment Checklist (MBI-C) and the Neuropsychiatric Inventory Questionnaire severity (NPI-Q-S) and distress (NPI-Q-D) scales. Multiple linear regressions (MLR) assessed the association of Braak stages with baseline NPS and the annual change in NPS scores. At baseline, stages I-II, III-IV, and V-VI were associated with higher MBI-C, NPI-Q-S, and NPI-Q-D scores. Stages V-VI were associated with a significant annual increase in MBI-C scores. These findings suggest that tau accumulation may manifest clinically with an increase in NPS, which seems to be an early event in AD pathophysiology. Moreover, PET-based Braak staging appears to be a good predictor of NPS severity progression.

Psychotic symptoms (hallucinations and delusions) are a type of neuropsychiatric symptom found during Alzheimer's Disease (AD).

This systematic review aims to comprehensively capture, analyse, and evaluate the body of evidence that has investigated associations between brain regions/networks and psychotic symptoms in AD.

The protocol, created according to the PRISMA guidelines, was pre-registered on OSF (https://osf.io/tg8xp/). Searches were performed using PubMed, Web of Science and PsycInfo. A partial coordinate-based meta-analysis (CBMA) was performed based on data availability.

Eighty-two papers were selected: delusions were found to be associated mainly with right fronto-temporal brain regions and the insula; hallucinations mainly with fronto-occipital areas; both were frequently associated with the anterior cingulate cortex. The CBMA, performed on the findings of fourteen papers on delusions, identified a cluster in the frontal lobe, one in the putamen, and a smaller one in the insula.

The available evidence highlights that key brain regions, predominantly in the right frontal lobe, the anterior cingulate cortex, and temporo-occipital areas, appear to underpin the different manifestations of psychotic symptoms in AD and MCI. The fronto-temporal areas identified in relation to delusions may underpin a failure to assimilate correct information and consider alternative possibilities (which might generate and maintain the delusional belief), and dysfunction within the salience network (anterior cingulate cortex and insula) may suggest a contribution for how internal and external stimuli are identified; the fronto-occipital areas linked to hallucinations may indicate diminished sensory processing and non-optimal predictive processing, that together contribute to misinterpretation of stimuli and misperceptions; the fronto-temporal and occipital areas, as well as the anterior cingulate cortex were linked to the psychotic cluster.

While antipsychotics are often prescribed for behavioral and psychological symptoms of dementia (BPSD), typically on an off-label basis, these medications have serious adverse effects. This study investigated the long-term use of antipsychotics among inpatients with dementia displaying severe BPSD, focusing on how prescriptions change over time.

Medical charts at Kusakabe Memorial Hospital were retrospectively reviewed from October 2012 to September 2021. The study included patients diagnosed with dementia, admitted for BPSD, and were continuing antipsychotics at 3 months of their admission. Antipsychotic dosages were categorized as high (≥300 mg/d), medium (100-300 mg/d), and low (<100 mg/d) based on chlorpromazine equivalents and tracked until 15 months during hospitalization. Binary logistic regression was used to identify factors associated with dosage reductions between months 3 and 6.

This study involved 188 patients, with an average age of 81.2 years, 67% of whom were diagnosed with Alzheimer's dementia. At 3 months, 15.4% were taking high, 44.1% on medium, and 40.4% on low dosages of antipsychotics. The highest average dosage was observed at 3 months, with a subsequent decrease over time. By the 12th month, 20-30% of patients in all dosage categories had stopped their antipsychotic medication. Significant factors for dosage reduction included higher initial doses (OR 1.003, 95%Cl: 1.001-1.006, P=0.01) and male gender (OR 2.481, 95%Cl: 1.251-4.918, P=0.009).

A trajectory of antipsychotic dosage in inpatients with severe BPSD has rarely been reported. This research emphasizes the need for personalized strategies in managing long-term pharmacotherapy for this vulnerable group of patients.

Alzheimer's disease (AD) is a progressive, degenerative brain disorder that impairs memory and thinking skills, leading to significant economic and humanistic burdens. It is associated with various neuropsychiatric symptoms (NPS) such as anxiety, agitation, depression, aggression, apathy, and psychosis. NPSs are common in patients with AD, affecting up to 97% of individuals diagnosed with AD. The severity of NPS is linked to disease progression and cognitive decline. NPS in Alzheimer's disease leads to increased morbidity, mortality, caregiver burden, earlier nursing home placement, and higher healthcare costs. Despite their significant impact, clinical research on NPS in AD is limited. In clinical settings, accurately distinguishing and diagnosing NPS related to AD remains a challenge. Additionally, conventional treatments for NPS in AD are often ineffective, highlighting the need for new therapies that target these specific symptoms. Understanding these comorbidities can aid in early diagnosis and better management of AD. In this review, we provide a summary of the various neurological and psychiatric symptoms (NPS) associated with AD and new candidates under development for the treatment of NPS based on their therapeutic targets and mechanisms. On top of the conventional NPS studied so far, this review adds recent advancements in the understanding of social functional impairment in AD. This review also provides information that can contribute to the advancement of studies and translational research in this field by emphasizing therapeutic targets and mechanisms of action focused on AD-related NPS rather than conventional mechanisms targeted in AD drug development. Above all, considering the relative lack of research in this new field despite the importance of clinical, medical, and translational research, it may increase interest in NPS in AD, its pathophysiological mechanisms, and potential therapeutic candidates such as molecules with antioxidant potential.

Alzheimer's disease (AD) is associated with gradual memory loss and anxiety which affects ~75% of AD patients. This study investigated whether AD-associated anxiety correlated with modulation of extrasynaptic δ-subunit-containing GABAA receptors (δ-GABAARs) in experimental mouse models of AD.

We combined behavioural experimental paradigms to measure cognition performance, and anxiety with neuroanatomy and molecular biology, using familial knock-in (KI) mouse models of AD that harbour β-amyloid (Aβ) precursor protein App (AppNL-F) with or without humanized microtubule-associated protein tau (MAPT), age-matched to wild-type control mice at three different age windows.

AppNL-F KI and AppNL-F/MAPT AD models showed a similar magnitude of cognitive decline and elevated magnitude of anxiety correlated with neuroinflammatory hallmarks, including triggering receptor expressed on myeloid cells 2 (TREM2), reactive astrocytes and activated microglia consistent with accumulation of Aβ, tau and down-regulation of Wnt/β-catenin signalling compared to aged-matched WT controls. In both the CA1 region of the hippocampus and dentate gyrus, there was an age-dependent decline in the expression of δ-GABAARs selectively expressed in parvalbumin (PV)-expressing interneurons, encapsulated by perineuronal nets (PNNs) in the AD mouse models compared to WT mice. In vivo positive allosteric modulation of the δ-GABAARs, using a δ-selective-compound DS2, decreased the level of anxiety in the AD mouse models, which was correlated with reduced hallmarks of neuroinflammation, and 'normalisation' of the expression of δ-GABAARs.

Our data show that the δ-GABAARs could potentially be targeted for alleviating symptoms of anxiety, which would greatly improve the quality of life of AD individuals.

Supportive Care is a person-centred approach encompassing non-pharmacological interventions targeted towards persons with dementia to contain the effects of their behavioural disorders, improving their quality of life.

To investigate the effects of lockdown restrictions during the first wave of COVID-19 pandemic on behavioural symptoms of patients involved in a Supportive Care programme in an Italian nursing home.

Analysis is based on Neuropsychiatric Inventory (NPI) scores and related symptoms data collected before (October/November 2019) and after (July 2020) the introduction of COVID-19 restrictions on a non-random sample of 75 patients living in two units of the facility: 38 involved in a Supportive Care programme and 37 receiving standard care (Control). Group performances were compared over time according to univariate statistics and Latent Class Analysis (LCA).

NPI scores and number of reported symptoms in NPI evaluations increased over time among Supportive Care patients with dementia and decreased in the Control group. Differences are statistically significant. LCA resulted in 3-classes and 5-classes specifications in the two time-occasions.

Supportive Care patients showed a worsening in behavioural and psychological symptoms after the first pandemic wave, as opposed to the elderly not involved in the programme. LCA showed that patients in the two groups differed according to the combinations of NPI symptoms.

The discontinuation of a Supportive Care programme due to COVID-19 restrictions had strong negative effects on nursing home persons with dementia involved in the programme: Supportive Care interventions are important in controlling the psycho-behavioural symptoms associated with dementia.

Anxiety is a neuropsychiatric symptom (NPS) of Alzheimer disease (AD) patients which has been studied primarily in prospective and retrospective studies of clinically diagnosed AD. However, this can be confounded by other primary etiologies. Moreover, anxiety has not been comprehensively studied in autopsy-confirmed AD cases across subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia stages. We conducted a retrospective longitudinal analysis of 212 participants with autopsy-confirmed AD, followed from 1986-2013 at the NYU Alzheimer's Disease Research Center with staging via the Global Deterioration Scale and NPS assessed via BEHAVE-AD. We found that anxiety varied uniquely with stage and was the most common NPS in SCD and MCI (35-40% prevalence). ApoE4 carriage associated with a higher rate of anxiety only at mild dementia. Anxiety in SCD associated with cerebral amyloid angiopathy and arteriosclerosis on brain autopsy, but there were no such associations with concomitant neuropathology at MCI and mild dementia. Anxiety associated with increased progression rate (∼2.5-fold) from SCD to MCI/dementia stages, but not from MCI to dementia. These results suggest an important relationship between anxiety and AD, especially at the preclinical stage. This warrants further study of anxiety as a possible modifiable factor of disease experience and course.

Neuropsychiatric symptoms (NPS) are nearly universal in dementia; some cross-sectional studies of NPS in dementia have found racial/ethnic differences, though it is unknown if NPS prevalence differs among racial/ethnic groups before and after dementia diagnosis.

Participants were followed annually at Alzheimer's Disease Centers and were assessed on the Neuropsychiatric Inventory-Questionnaire (NPI-Q) with at least one follow-up visit at which they were diagnosed with dementia. Descriptive statistics were generated by race/ethnicity. NPS were modeled over time as a function of race/ethnicity and with diagnosis date as the baseline.

NPS were present in 95% in at least one time point. After adjusting for covariates, there were no statistically significant differences in NPI-Q total scores among racial/ethnic groups at the time of and after dementia diagnosis.

Findings from our prospective cohort study suggest that when individuals are matched at the time of conversion to dementia, there are no racial/ethnic differences in NPS.

Neuropsychiatric symptoms of dementia are frequent and increase caregiver burden.Prior studies reported more neuropsychiatric symptoms (NPS) in Black compared to White individuals with dementia.National Alzheimer's Coordinating Center Black, White, and Hispanic participants did not differ in NPS at the time of dementia diagnosis.

In psychogeriatric units for patients with dementia and behavioral problems, aggression is prevalent. Predictions and timely interventions of aggression are essential to create a safe environment and prevent adverse outcomes. Our study aimed to determine whether aggression severity early during admission to these units could be used as an indicator of adverse outcomes.

During one year, all aggressive incidents on a psychogeriatric unit were systematically recorded using the Revised Staff Observation of Aggression Scale (SOAS-R). The study investigated the link between the severity of incidents within the first 48 hours of admission and adverse outcomes.

All patients included in the study were admitted to a psychogeriatric unit for dementia and behavioral problems between November 2020 and October 2021.

The study population was categorized into groups according to the level of aggression severity during the first 48 hours of admission. The impact of aggression severity on the duration of admission, aggression frequency and severity during admission, medication usage at discharge, discharge destination, and mortality risk were examined.

During the initial 2 days of admission, 9 of 88 patients had 1 or more severe aggression incidents. An early manifestation of severe aggression was significantly associated with more incidents during hospitalization, a higher total SOAS-R score, and a sevenfold higher 1-year mortality risk compared with patients who did not or only mildly manifested aggression in the first 48 hours of admission.

An early manifestation of aggression not only poses a direct safety risk to all involved but is also an early indicator of patients at risk for more detrimental outcomes, specifically mortality risk. By identifying patients at higher risk for adverse outcomes early, health care providers can provide preventive or timelier interventions, mitigating the risk of adverse outcomes and optimizing care services.

Alzheimer's Disease (AD) is characterized by a range of behavioral alterations, including memory loss and psychiatric symptoms. While there is evidence that molecular pathologies, such as amyloid beta (Aβ), contribute to AD, it remains unclear how this histopathology gives rise to such disparate behavioral deficits. One hypothesis is that Aβ exerts differential effects on neuronal circuits across brain regions, depending on the neurophysiology and connectivity of different areas. To test this, we recorded from large neuronal populations in dorsal CA1 (dCA1) and ventral CA1 (vCA1), two hippocampal areas known to be structurally and functionally diverse, in the APP/PS1 mouse model of amyloidosis. Despite similar levels of Aβ pathology, dCA1 and vCA1 showed distinct disruptions in neuronal population activity as animals navigated a virtual reality environment. In dCA1, pairwise correlations and entropy, a measure of the diversity of activity patterns, were decreased in APP/PS1 mice relative to age-matched C57BL/6 controls. However, in vCA1, APP/PS1 mice had increased pair-wise correlations and entropy as compared to age matched controls. Finally, using maximum entropy models, we connected the microscopic features of population activity (correlations) to the macroscopic features of the population code (entropy). We found that the models' performance increased in predicting dCA1 activity, but decreased in predicting vCA1 activity, in APP/PS1 mice relative to the controls. Taken together, we found that Aβ exerts distinct effects across different hippocampal regions, suggesting that the various behavioral deficits of AD may reflect underlying heterogeneities in neuronal circuits and the different disruptions that Aβ pathology causes in those circuits.

Mild behavioural impairment (MBI) is an emergent and persistent neuropsychiatric symptom (NPS) in subjects aged 50 and older who are at risk for cognitive decline. We examined the prevalence of MBI across the spectrum from cognitively normal (CN), mild cognitive impairment (MCI), to dementia, and further investigated the association between the MBI domain and cognitive and functional impairment.

MBI was assessed in 2337 elderly patients in the Alzheimer's Disease Neuroimaging Initiative database (mean age, 73.04 years; 52.8% male). Among the subjects, 868 (37.1%) had normal cognition, 1066 (45.6%) had MCI, and 403 (17.2%) had mild Alzheimer's dementia (AD). MBI was evaluated in accordance with the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment diagnostic criteria for MBI, utilising the Neuropsychiatric Inventory. We compared the prevalence of the MBI domain with CN using multinominal logistic regression analysis and further quantified the magnitude of the association between MCI/AD and the MBI domains by calculating the population attributable risk (PAR). We assessed the association between the MBI domains and cognitive and functional impairment using simultaneous linear regression analysis.

The most common MBI domains in each diagnostic group were affective dysregulation followed by impulse dyscontrol, decreased motivation, social inappropriateness, and abnormal perception or thought content. The PARs for MBI domains in subjects with MCI or AD were respectively: 16.60% and 24.34% for affective dysregulation; 3.72% and 18.06% for impulse dyscontrol; 4.78% and 14.13% for decreased motivation, 1.91% and 2.29% for social inappropriateness; and 0.68% and 3.85% for abnormal perception or thought content. All MBI domains except for social inappropriateness were significantly associated with a higher 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale total score. All MBI domains were significantly associated with a higher Functional Activities Questionnaire total score.

Our findings show that MBI is highly prevalent across subjects with CN, MCI, and AD and is associated with cognitive and functional decline. MBI could be a crucial clinical phenotype relevant to the risk of cognitive and functional impairment, and provides a useful dimension pertinent to diagnostic approaches.

Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes.

Genome-wide association meta-analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P).

AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations.

AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development.

It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not.Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations.

Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are two common atypical Alzheimer's disease (AD) variants. Little is known about behavioral and neuropsychiatric symptoms or activities of daily living (ADLs) in PCA and LPA, and whether they differ across syndromes.

To characterize the behavioral and neuropsychiatric profiles and ADLs of PCA and LPA and compare presence/absence and severity of symptoms between syndromes.

Seventy-eight atypical AD patients, 46 with PCA and 32 with LPA, completed the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Cambridge Behavioral Inventory-Revised (CBI-R) at baseline and longitudinally over-time. Mann-Whitney U and Fisher's Exact Tests assessed for differences in symptoms between the two syndromes with significance set at p≤0.01. To eliminate demographic differences as confounders the groups were matched, and differences reanalyzed.

PCA were younger at onset (p = 0.006), at time of baseline assessment (p = 0.02) and had longer disease duration (p = 0.01). Neuropsychiatric symptoms were common in PCA and LPA, although more common and severe in PCA. At baseline, PCA had a higher NPI-Q total score (p = 0.01) and depression subscore (p = 0.01) than LPA. Baseline total CBI-R scores were also higher in PCA than LPA (p = 0.001) with PCA having worse scores in all 10 CBI-R categories. Longitudinally, there was no difference between groups on the NPI-Q. However, on the CBI-R, PCA had faster rates of worsening on self-grooming (p = 0.01) and self-dressing (p = 0.01) compared to LPA.

Behavioral and neuropsychiatric symptoms are common in PCA and LPA although these symptoms are more common and severe in PCA.

Delusional ideations, one of neuropsychiatric symptoms (NPSs), are frequently shown in the long-term progression of Alzheimer's disease (AD), and comorbid with other NPSs including depression or agitation. Despite various types of delusional ideations, the comorbidity between each delusional ideation and depressive symptoms has not been discussed.

The present cross-sectional study is aimed at testing the hypothetical mechanism of comorbid pattern in AD.

Among 421 patients with AD, we analyzed the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease to compare age, sex, racial type, Mini-Mental State Examination (MMSE) scores, and Neuropsychiatric Inventory (NPI) depression score of between the presence and absence of each delusional ideation (delusion of persecution, theft, jealousy, abandonment, phantom boarder, Capgras syndrome, misidentification of place, or television sign). Next, with the stratification based on MMSE score of < or > = 15 points, we further explored association between delusional ideation and depressive symptom that was found significances in the primary analysis.

Among eight subtypes of delusional ideations, depression score was higher in those with persecution delusion or Capgras syndrome. Moreover, the Capgras syndrome was associated with presence of depression in severer global cognitive impairment status.

As comorbid NPSs of delusional ideation in AD, depressive severity is associated with specific delusional subtype: persecution delusion and Capgras syndrome. Capgras syndrome may be attributable to severe cognitive impairment in addition to depressive symptom. The consideration of pathogenetic differences in the distinct delusional ideations may be helpful for clinicians to select the treatment strategy.

Behavioral symptoms are commonly observed in the course of dementia. This study aimed to assess the association of the diagnosis of a cluster of behavioral symptoms (e.g., agitation, aggression, psychotic symptoms, and delirium/wandering) with the likelihood of subsequent institutionalization.

A retrospective cohort study of adults aged 65 and above diagnosed with dementia identified in the IBM® MarketScan® Multistate Medicaid database between October 01, 2015, and September 30, 2019, was conducted. The index date was defined as the first diagnosis date of dementia. The presence or absence of behavioral symptoms was identified in the 6 months prior to the index date (baseline). Institutionalization was evaluated 12 months (follow-up) post the index date. The association between diagnosed behavioral symptoms during the baseline period and institutionalization in the follow-up period was assessed using a multivariable logistic regression, adjusting for baseline sociodemographic and clinical characteristics.

The study cohort included 40,714 patients with dementia. A diagnosis of behavioral symptoms was found among 2,067 (5.1%) patients during the baseline period. An increased likelihood of institutionalization was found during the follow-up among patients with agitation and aggression in baseline (OR = 1.51 (95% CI: 1.18-1.92)) compared to patients without these symptoms at baseline. Patients with psychotic symptoms in baseline had significantly higher odds of getting institutionalized during the follow-up compared to patients without psychotic symptoms in baseline (OR = 1.36 (95% CI: 1.20-1.54)). Similarly, patients with symptoms of delirium and wandering in baseline had a higher likelihood of institutionalization than patients without these symptoms at baseline (OR = 1.61 (95% CI: 1.30-1.99)).

Several diagnosed behavioral symptoms were associated with a higher risk of institutionalization among older adults with dementia and should be considered when planning treatment strategies for the effective management of the condition.

Neuropsychiatric symptoms (NPSs) are common in neurodegenerative diseases; however, little is known about the prevalence of NPSs in Hispanic populations.

Using data from community-dwelling participants age 65 years and older enrolled in the 10/66 study (N = 11,768), we aimed to estimate the prevalence of NPSs in Hispanic populations with dementia, parkinsonism, and parkinsonism-dementia (PDD) relative to healthy aging. The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPSs.

NPSs were highly prevalent in Hispanic populations with neurodegenerative disease; approximately 34.3%, 56.1%, and 61.2% of the participants with parkinsonism, dementia, and PDD exhibited three or more NPSs, respectively. NPSs were the major contributor to caregiver burden.

Clinicians involved in the care of elderly populations should proactively screen for NPSs, especially in patients with parkinsonism, dementia, and PPD, and develop intervention plans to support families and caregivers. Highlights Neuropsychiatric symptoms (NPSs) are highly prevalent in Hispanic populations with neurodegenerative diseases. In healthy Hispanic populations, NPSs are predominantly mild and not clinically significant. The most common NPSs include depression, sleep disorders, irritability, and agitation. NPSs explain a substantial proportion of the variance in global caregiver burden.

Depression is among the most frequent psychiatric comorbid conditions in Alzheimer disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge, and the data on the efffcacy of current antidepressants used clinically for depressive symptoms in patients with AD remain inconclusive. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD. Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 24 months of age and age- and sex-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT) were implemented to assess the abilities of learning and memory, and the open field test (OFT) and the tail suspension test (TST) were used to assess depression-like behavior. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identified by orthogonal projections to latent structures discriminant analysis (OPLS-DA). Most neurotransmitters exert their effects by binding to the corresponding receptor, so the expression of relative receptors in the hippocampus of mice was detected using Western blot. Compared to WT mice, 3×Tg-AD mice displayed significant cognitive impairment in the PAT and depression-like behavior in the OFT and TST. They also showed significant decreases in the levels of L-tyrosine, norepinephrine, vanillylmandelic acid, 5-hydroxytryptamine, and acetylcholine, in contrast to significant increases in 5-hydroxyindoleacetic acid, L-histidine, L-glutamine, and L-arginine in the hippocampus. Moreover, the expression of the alpha 1a adrenergic receptor (ADRA1A), serotonin 1 A receptor (5HT1A), and γ-aminobutyric acid A receptor subunit alpha-2 (GABRA2) was significantly downregulated in the hippocampus of 3×Tg-AD mice, while histamine H3 receptor (H3R) expression was significantly upregulated. In addition, the ratio of phosphorylated cAMP-response element-binding protein (pCREB) and CREB was significantly decreased in the hippocampus of 3×Tg-AD mice than WT mice. We demonstrated in the present study that aged female 3×Tg-AD mice showed depression-like behavior accompanied with cognitive dysfunction. The complex and diverse mechanism appears not only relevant to the imbalance of multiple neurotransmitter pathways, including the transmitters and receptors of the monoaminergic, GABAergic, histaminergic, and cholinergic systems, but also related to the changes in L-arginine and CREB signaling molecules.

Due to the increasing prevalence of Alzheimer's disease (AD) and the limited efficacy of pharmacological treatment, the interest in non-pharmacological interventions, e.g., cognitive stimulation therapy (CST), to improve cognitive dysfunction and the quality of life of AD patients are on a steady rise.

Here, we examined the efficacy of a CST program specifically conceptualized for AD dementia patients and the neural mechanisms underlying cognitive or behavioral benefits of CST.

Using neuropsychological tests and MRI-based measurements of functional connectivity, we examined the (neuro-) psychological status and network changes at two time points: pre vs. post-stimulation (8 to 12 weeks) in the intervention group (n = 15) who received the CST versus a no-intervention control group (n = 15).

After CST, we observed significant improvement in the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale, cognitive subsection (ADAS-cog), and the behavioral and psychological symptoms of dementia (BPSD) scores. These cognitive improvements were associated with an up-regulated functional connectivity between the left posterior hippocampus and the trunk of the left postcentral gyrus.

Our data indicate that CST seems to induce short-term global cognition and behavior improvements in mild to moderate AD dementia and enhances resting-state functional connectivity in learning- and memory-associated brain regions. These convergent results prove that even in mild to moderate dementia AD, neuroplasticity can be harnessed to alleviate cognitive impairment with CST.

Neuropsychiatric symptoms (NPS) are a risk factor for dementia; however, their prevalence and severity among ethnoracial groups are poorly understood.

We used data from the National Alzheimer's Coordinating Center (NACC) (n = 6958; ≥50 years old). Cognitively normal participants at baseline, without any NPS or dementia diagnosis, had at least one follow-up. Survival analyses assessed the hazard ratio for 12 NPS models and progression to cognitive impairment. Propensity score weighting (PSW) matched participants on age, sex, education, and race/ethnicity.

All 12 NPS were significantly associated with progression to cognitive impairment. In the PSW models, compared to whites, Black/African Americans were more likely to progress to cognitive impairment across all 12 NPS models, followed by Hispanic, and then Asian participants.

PSW minimized selection bias to provide robust risk estimates. There is a higher risk of progressing to cognitive impairment for ethnoracial groups with NPS. Tailored screening of NPS and cognitive impairment should incorporate patient and caregiver reports.

Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely provision of pharmacological interventions for apathy is greatly needed.

A systematical literature review of existing studies was conducted up to 30 May 2023 in several databases (PubMed, PsychInfo, Cochrane, Google Scholar, etc.) that included randomized controlled trials (RCTs) and meta-analyses assessing pharmacological treatments for apathy in aging neurocognitive disorders. The quality of the studies was appraised.

In patients with Alzheimer's Disease (AD), donepezil, galantamine, rivastigmine, methylphenidate, and gingko biloba were proven efficacious for apathy, while rivastigmine, cognitive enhancer IRL752 and piribedil were found to be beneficial in patients with Parkinson's Disease (PD) and agomelatine in patients with Frontotemporal Dementia (FD). The extensive proportion of RCTs in which apathy was used as a secondary outcome measure, along with the considerable methodological heterogeneity, did not allow the evaluation of group effects.

Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital.

Up to 90% of people with dementia experience behavioural and psychological symptoms of dementia (BPSD) as part of their illness. Psychotropics are not recommended as the first-line treatment of BPSD because older people are more prone to adverse reactions. In this study, we evaluate the impact of the Finnish clinical guidelines of BPSD (published in 2017) on psychotropic use in people with dementia.

This study is based on Finnish Prescription Register data from 2009 to 2020. The data included all community-dwelling Finnish people aged ≥65 and who had anti-dementia medication purchases (n = 217,778). We used three-phased interrupted time series design to evaluate the changes in levels and trends of monthly (n = 144) psychotropic user rates compared with the predicted trends. In addition, we evaluated the changes in levels and trends of monthly new psychotropic user rates.

The level of monthly psychotropic user rate decreased non-significantly during the intervention period (β -0.057, P = 0.853), and during the post-intervention period, there was an increase in the level (β 0.443, P = 0.091) and slope (β 0.199, P = 0.198), but not statistically significant. The level of monthly new psychotropic user rate (β -0.009, P = 0.949) during the intervention period and the level (β 0.044, P = 0.714) and slope (β 0.021, P = 0.705) during the post-intervention period were almost unchanged.

Results may indicate possible challenges in deprescribing and better adherence to the guidelines at the beginning of BPSD treatment. Further research into the barriers to implement BPSD guidelines and the availability of non-pharmacological treatments is needed.

Repetitive transcranial magnetic stimulation is a noninvasive intervention, can significantly reduce behavioral and psychological symptoms and cognitive impairment in AD patients. Only few cases have been reported the adverse reactions after the treatment. This report described the different adverse reactions after repetitive transcranial magnetic stimulation with different parameters.

This article reports a patient with dementia complicated with mental behavior disorder who was treated with repetitive transcranial magnetic stimulation (rTMS) in spite of poor drug response. First, 1 Hz rTMS was initiated. After 1 month, the patient showed improved symptoms of mental behavior, decreased cognitive function and prolonged sleep duration. After switched to 10 Hz rTMS, the patient's cognitive function and mental behavior abnormalities improved, and the sleep time returned to normal. However, epilepsy occurred after one session and was changed to 0.8 Hz rTMS treatment. The patient's symptoms improved and did not have seizure.

Repetitive transcranial magnetic stimulation has a positive effect on cognitive function and Behavioral And Psychological Symptoms Of Dementia, and adverse reactions are inevitable. Playing personalized treatment according to the patients can reduce occurrence of adverse reactions.

While racial, ethnic, and socioeconomic group disparities in cognitive impairment and dementia prevalence are well-documented among community-dwelling older adults, little is known about these disparity trends among older adults receiving Medicaid-funded home- and community-based services (HCBS) in lieu of nursing home admission. The authors determined how dementia prevalence and cognitive impairment severity compare by race, ethnicity, educational attainment, and neighborhood context in a Medicaid HCBS population.

A cross-sectional study in Connecticut.

Adults age ≥65 in the HCBS program, January-March 2019 (N = 3,520).

The data source was Connecticut's HCBS program Universal Assessment tool. The authors employed two outcomes: Cognitive Performance Scale (CPS2), a 9-point measure ranging from cognitively intact-very severe impairment; and presence or not of either diagnosed dementia or CPS2 score ≥4 (major impairment). Neighborhood context was measured using the Social Vulnerability Index (SVI).

Cohort characteristics: 75.7% female; mean(SD) age = 79.1(8.2); Non-Hispanic White = 47.8%; Hispanic = 33.6%; Non-Hispanic Black = 15.9%. Covariate-adjusted multivariate analyses revealed no dementia/major impairment prevalence differences among White, Black, and Hispanic individuals, but impairment severity was greater among Hispanic participants (b = 0.22; p = 0.02). People with more than HS education had less severe impairment (b = -0.12; p <0.001) and lower likelihood of dementia/major impairment (AOR = 0.61; p <0.001). Dementia/major impairment likelihood and impairment severity were greater in less socially vulnerable neighborhoods.

Racial and ethnic group differences in cognitive impairment are less pronounced in Medicaid-funded HCBS cohorts than in other community-dwelling older adult cohorts. SVI results suggest that, among other possible explanations, older adults with dementia may move to lower social vulnerability neighborhoods where supportive family members reside.

This study examined relationships between personality disorder (PD) features, Big Five personality traits, and interpersonal problems with anxiety.

Older adults (N = 130) completed the Geriatric Anxiety Scale, Coolidge Axis Two Inventory, Big Five Inventory-2, and Circumplex Scales of Interpersonal Problems. Pearson correlation analyses were used to assess simple relationships between anxiety with PD features (CATI scales), Big Five personality domains (BFI-2 scales), and interpersonal problems (CSIP scales). Multiple linear regression analyses were performed to determine the extent to which the PD scales of the CATI, the personality scales of the BFI-2, and the scales of the CSIP explained variance in anxiety.

Anxiety was positively correlated with 13 of 14 PD scales, ranging from .23 (Narcissistic) to .61 (Depressive). Regarding Big Five personality traits, anxiety was negatively associated with Agreeableness (-.23), Conscientiousness (-.30), and Extraversion (-.31) but was positively associated with Negative Emotionality (.56). Regarding interpersonal problems, anxiety was positively related to all eight CSIP scales, ranging from Self-sacrificing (.30) to Distant/Cold (.62). Regression analyses indicated that PD features accounted for the most variance in anxiety symptoms (53%), followed by interpersonal problems (46%), and Big Five personality traits (33%).

Anxiety appears to be meaningfully associated with PD features, several aspects of Big Five personality traits, and interpersonal problems, suggesting that these variables may play important roles in the development and maintenance of anxiety, or vice versa. Our findings especially speak to the growing awareness of the deleterious impact of PD features on clinical syndromes in later life, as evidenced by strong comorbidities with anxiety.

With the geriatric population in the United States growing rapidly, the prevalence of dementia is expected to rise concomitantly. As dementia is an invariably progressive and terminal illness, planning for and managing end of life care in dementia is an important part of the overall process of dementia care. Unfortunately, this is often neglected outside of formal palliative and hospice medicine training programs and geriatric psychiatrists are left without preparation on how to manage, as well as counsel patients and families on, this important phase of dementia care. This review aims to explore the potential contributors to this historic disparity in geriatric education and care delivery, as well as its impact, while also attempting to shift the field's focus toward a palliative approach to dementia care. To begin to accomplish this, this review explores the natural illness history/disease trajectory of the various dementing illnesses, as well as the topic of prognostication as it pertains to the end of life for patients with dementia and how this information can be used in advanced care planning and symptom management.

To examine whether associations between individual neuropsychiatric symptoms (NPS) and incident Alzheimer's dementia (AD) differ in men versus women.

Data were acquired from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set. Two sets of older (≥ 60 years) participants were formed: one of cognitively unimpaired (CU) individuals, and one of participants with mild cognitive impairment (MCI). NPS were assessed using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models examined associations between individual NPS and AD incidence separately for each participant set. These models featured individual NPS, sex, NPS by sex interactions as well as a number of covariates.

The analysis involved 9,854 CU individuals followed for 5.5 ± 3.8 years and 6,369 participants with MCI followed for 3.8 ± 3.0 years. NPS were comparably associated with future AD in men and women with MCI. Regarding CU participants, the following significant sex by NPS interactions were noted: female sex moderated the risk conferred by moderate/severe apathy (HR = 7.36, 3.25-16.64) by 74%, mitigated the risk conferred by moderate/severe depression (HR = 3.61, 2.08-6.28) by 52%, and augmented the risks conferred by mild depression (HR = 1.00, 0.60-1.68) and agitation (HR = 0.81, 0.40-1.64) by 83% and 243%, respectively.

Apathy, depression and agitation were differentially associated with incident AD in CU men and women. No individual NPS was associated with different risks of future AD in men versus women with MCI.

Major depressive disorder and Alzheimer's disease are common among older people, frequently co-occur and severely impact the quality of life. Unfortunately, data on the efficacy of pharmacologic treatment of depressive symptoms in patients with the neurodegenerative disease remain inconclusive. The heterogeneity of treatment study designs, from varying diagnostic specificity to diverse outcome measures, contributes to conflicting evidence across single trials and meta-analyses. In this literature review, we focus on commercially available products for antidepressant treatment in demented individuals and show how insights from randomized controlled trials could still guide and be aligned with common clinical practice.

Few studies have examined the association of comorbid depression with health-care utilization among dementia patients. This study compared health-care utilization between dementia patients with and without comorbid depression.

Using Taiwan's National Health Insurance Research Database, we identified 10,710 patients with newly diagnosed dementia between 2005 and 2014: 1785 had comorbid depression (group 1) and 8925 did not (group 2). Patients were tracked for 1 year to evaluate outpatient, emergency, and inpatient service utilization and length of hospital stay (LOS). Multivariable regression was applied to examine the association between comorbid depression and health-care utilization and analyze factors associated with inpatient visits and LOS.

Group 1 had significantly fewer outpatient visits (β = -0.115; p < 0.001), more inpatient visits (β = 0.157; p = 0.005), and a longer LOS (β = 0.191; p < 0.001) than did group 2. The groups did not differ significantly in emergency visits (β = 0.030; p = 0.537). In group 1, age, gender, and specific comorbidities were predictors of inpatient visits; those factors and salary-based insurance premiums were predictors of LOS.

Group 1 utilized less outpatient care but more inpatient care, suggesting health-care service for these patients may be needed to improvement.

Limited research is available on the real-world experiences of patients with dementia with Lewy bodies (DLB). This study evaluated clinical events, healthcare utilization, and healthcare costs of patients with DLB vs other dementia types with psychosis (ODP). Study patients included commercial and Medicare Advantage with Part D enrollees aged ≥40 years with evidence of DLB and ODP from 6/01/2015‒5/31/2019. Compared with patients with ODP, more patients with DLB had clinical events including anticholinergic effects, neurologic effects, and cognitive decline. Patients with DLB used more healthcare resources with greater dementia-related office and outpatient visits and psychosis-related inpatient stays and office, outpatient, and emergency visits compared with their ODP patient counterparts. Patients with DLB also incurred higher healthcare costs for all-cause and dementia-related office visits and pharmacy fills, and psychosis-related total costs. Understanding the clinical and economic impact of DLB and ODP is important to improve care for patients with dementia.

Despite the burden on patients and caregivers, there are no approved therapies for the neuropsychiatric symptoms of Alzheimer's disease (NPS-AD). This is likely due to an incomplete understanding of the underlying mechanisms.

To review the neurobiological mechanisms of NPS-AD, including depression, psychosis, and agitation.

Understanding that genetic encoding gives rise to the function of neural circuits specific to behavior, we review the genetics and neuroimaging literature to better understand the biological underpinnings of depression, psychosis, and agitation.

We found that mechanisms involving monoaminergic biosynthesis and function are likely key elements of NPS-AD and while current treatment approaches are in line with this, the lack of effectiveness may be due to contributions from additional mechanisms including neurodegenerative, vascular, inflammatory, and immunologic pathways.

Within an anatomic-genetic framework, development of novel effective biological targets may engage targets within these pathways but will require a better understanding of the heterogeneity in NPS-AD.

This study aimed to systematically review and meta-analyse the prevalence of sleep disturbances in people with dementia and examine demographic predictors and whether overall prevalence has changed over time. We searched Embase, MEDLINE and PsycINFO for studies reporting the prevalence of sleep disturbances in people with dementia living at home. We meta-analysed the data and calculated the pooled prevalence of sleep disturbances in people with dementia overall and in dementia subtypes. We used meta-regressions to investigate the effects of study characteristics, publication dates and participant demographics. Eleven studies fulfilled the inclusion criteria. The pooled prevalence of any symptoms of sleep disturbance was 26 % (95 % confidence intervals, CI: 23-30 %; n = 2719) and of clinically significant sleep disturbance 19 % (13-25 %; n = 2753). The pooled prevalence of sleep disturbance symptoms was significantly lower among people with Alzheimer's disease (24 %; 16-33 %, n = 310) than Lewy body dementia (49 %; 37-61 %, n = 65). Meta-regression analysis did not find that publication year, participant's age, sex and study quality predicted prevalence. Sleep disturbances are common among people with dementia living in the community, especially in Lewy body dementia. There was no change in prevalence according to publication dates, suggesting treatment has not improved over time.

Younger-onset dementia accounts for about 5-10% of all dementias in Australia. Little data is available on neuropsychiatric symptoms in people with younger-onset dementia compared to those with older-onset dementia. This study aims to compare the types of neuropsychiatric symptoms and their clinico-demographic characteristics of people with younger-onset dementia and older-onset dementia who are referred to a specific dementia support service.

A 2-year retrospective observational cross-sectional analysis was undertaken on referrals with neuropsychiatric symptoms from Dementia Support Australia programmes. Neuropsychiatric symptoms were measured using the Neuropsychiatric Inventory total severity scores and distress scores. Contributing factors to neuropsychiatric symptoms for dementia groups were examined. Logistic regression was used to examine the relationship between individual neuropsychiatric symptoms and having older-onset dementia vs younger-onset dementia.

Of the 15,952 referrals, about 5% (n = 729, mean age: 60.7 years, standard deviation = 5.4) were individuals with younger-onset dementia. Referrals with older-onset dementia were more likely to be female (56%), whereas referrals with younger-onset dementia were more likely to be male (54%). There was a four times greater rate of frontotemporal dementia for those with younger-onset dementia (16.0%, n = 117) compared to those with older-onset dementia (2.8%, n = 427), χ² (1) = 366.2, p < 0.001. Referrals with younger-onset dementia were more likely to be referred from community settings and those with older-onset dementia were more likely to be from residential aged care. Overall, there was no difference in the severity and distress of neuropsychiatric symptoms between the two groups. Contributing factors to neuropsychiatric symptoms were different between the groups, with pain being more frequently endorsed for individuals with older-onset dementia whereas communication difficulties were more commonly identified for those with younger-onset dementia.

Clinico-demographics of referrals with younger-onset dementia differ from those with older-onset dementia. There were some differences in the characteristics of neuropsychiatric symptoms between younger-onset dementia and older-onset dementia. Our findings have implications for service provision and support for people with dementia at different ages.

Depressive symptomatology is associated with caregiver burden and poor health outcomes among dementia caregivers. Scholars called for a paradigm shift to focus on positive aspects of caregiving, in particular, meaning making during the caregiving journey. This study draws on the meaning making model and a generation perspective to predict depression among dementia caregivers from two generations, including Baby Boomers who were born between 1946 and 1964 and Generation X who were born between 1965 and 1980, using a configuration approach. Data was collected in a two-wave longitudinal design, from December 2019 to March 2021 in Hong Kong. A fuzzy-set qualitative comparative analysis resulted in six configurations with an overall solution consistency and overall solution coverage of 0.867 and 0.488, respectively. These configurations consist of a different combination of conditions that predict high depressive symptomatology among dementia caregivers in two generations. Specifically, generation is related to five out of six configurations. This study is the first to predict depression among dementia caregivers using a meaning making model from a generation perspective. It advances the understanding of factors contributing to high depressive symptomatology among dementia caregivers from two generations, thus contributing to the future development of generation-responsive assessments, interventions, and policies.