Apathy, characterized by diminished motivation, is a highly prevalent neuropsychiatric symptom in dementia. However, there is a substantial knowledge gap with regard to prevalence rates, neurobiological underpinnings, and effective treatments for apathy in pre-dementia states, including mild cognitive impairment (MCI) and mild behavioral impairment (MBI).

We conducted a comprehensive literature search using MEDLINE, Embase, and PsycINFO databases to identify available research on apathy in prodromal dementia.

Apathy has consistently been detected in individuals with MCI with varying prevalence rates, and only recently has literature discussed the prevalence of apathy in MBI. Few pharmacological treatments have been utilized for apathy, with galantamine and risperidone showing mild reductions in apathetic behaviors. Non-pharmacological interventions in prodromal dementia are beginning to be explored and show promise, but few studies have replicated those results.

More comprehensive guidelines for diagnosing apathy and further research investigating neurobiological mechanisms of apathy in MCI and MBI are required in order to effectively treat apathetic patients in prodromal dementia.

Affective and emotional symptoms such as depression, anxiety, euphoria, and irritability are common neuropsychiatric symptoms (NPS) in pre-dementia and cognitively normal older adults. They comprise a domain of Mild Behavioral Impairment (MBI), which describes their emergence in later life as an at-risk state for cognitive decline and dementia, and as a potential manifestation of prodromal dementia. This selective scoping review explores the epidemiology and neurobiological links between affective and emotional symptoms, and incident cognitive decline, focusing on recent literature in this expanding field of research.

Existing literature in prodromal and dementia states was reviewed, focusing on epidemiology, and neurobiology. Search terms included: “mild cognitive impairment,” “dementia,” “prodromal dementia,” “preclinical dementia,” “Alzheimer's,” “depression,” “dysphoria,” “mania,” “euphoria,” “bipolar disorder,” and “irritability.”

Affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often being harbingers of neurodegenerative change and progressive cognitive decline. Nosological constraints in distinguishing between pre-existing psychiatric symptomatology and later life acquired NPS limit historical data utility, but emerging research emphasizes the importance of addressing time frames between symptom onset and cognitive decline, and age of symptom onset.

Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies.

New onset of mood and behavioral changes in middle-aged patients are frequently the first manifestations of an unrecognized neurocognitive disorder. Impairment of social cognition, the cognitive ability to process social information coming from others, such as emotions, to attribute mental states to others, and to respond appropriately to them, is often at the origin of behavioral manifestations in neurodegenerative disorders.

This paper reviews the current literature on social cognition impairment in neurocognitive disorders, particularly in prodromal stages of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), idiopathic Parkinson's disease (IPD), and Lewy body dementia (LBD). The concepts of social cognition will be reviewed, including its impairment and neural basis, its clinical assessment, and the different therapeutic interventions available clinically.

Socially inappropriate behaviors, such as loss of empathy, inappropriateness of affect, and disinhibition are frequently reported in prodromal bvFTD and in prodromal AD. Lack of self-control, reduced perception of social cues, such as recognition of facial emotions and sarcastic speech, and impaired Theory of Mind all contribute to the neuropsychiatric symptoms and are secondary to neurodegeneration in specific brain regions. In contrasts to bvFTD and AD, deficits in social cognition in IPD occur later in the course of the disease and are often multifactorial in origin.

Through various manifestations, social inappropriateness is frequently the first clinical sign of a neurodegenerative process, especially in AD and bvFTD, years before noticeable impairment on classical neuropsychological assessment and brain atrophy on imaging.

Progression of dementia is often associated with the emergence of neuropsychiatric symptoms (NPS), though there is recent evidence that NPS may occur in prodromal dementia (PrD) and impact clinical course. Mood and anxiety symptoms are the NPS that tend to occur most frequently in PrD and thus have been most extensively studied. Comparatively, there has been little focus on psychotic symptoms in PrD.

The authors review the existing literature on psychosis in PrD, including the functional psychosis of early and late onset, with a focus on epidemiology, phenomenology, and clinical course and treatment considerations.

Patients with psychotic disorders at baseline such as schizophrenia may be more at risk for developing dementia over time, although this is not completely clear. Psychotic symptoms are likely more common in PrD than previously understood based on factor analysis studies, although they are much more common in established dementia. Variability in findings may reflect the heterogeneous nature of PrD studies to date and the lack of inclusion of patients with late onset psychosis in most clinical studies. The presence of psychosis in patients with PrD may be associated with a worse prognosis in terms of mortality and conversion to dementia.

Research to date suggests that psychosis in PrD may be more common than previously thought and impact clinical course negatively. Future studies incorporating patients with late onset psychotic disorders, and focusing on the impact of early recognition and treatment, are required to more fully understand the role of psychosis in PrD.

A dearth of population-based epidemiological research examines neuropsychiatric symptom (NPS) in sub-clinical populations across the spectrum from normal aging to mild cognitive impairment (MCI). The construct of mild behavioral impairment (MBI) describes the emergence of sustained and impactful NPS in advance of or in combination with MCI. This is the first epidemiological study to operationalize the recently published diagnostic criteria for MBI and determine prevalence estimates across the spectrum from cognitively normal to MCI.

MBI was assessed in 1,377 older (age range 72–79 years; 52% male; MCI ;= 133; cognitively normal, but-at-risk = 397; cognitively healthy = 847). MBI was assessed in accordance with the ISTAART-AA diagnostic criteria for MBI using the neuropsychiatric inventory.

34.1% of participants met the criteria for MBI. High prevalence of MBI across the cognitive spectrum was reported (48.9% vs. 43.1% vs. 27.6%). Irrespective of level of cognitive impairment, impulse dyscontrol (33.8% vs. 28.7% vs. 17.2%) and decreased motivation (32.3% vs. 26.2% vs. 16.3%) were the most frequently met MBI domains. MBI was more prevalent in men (χ2 = 4.98, p = 0.026), especially the domains of decreased motivation and impulse dyscontrol.

This study presents the first population-based prevalence estimates for MBI using the recently published ISTAART-AA diagnostic criteria. Findings indicate relatively high prevalence of MBI in pre-dementia clinical states and amongst cognitively healthy older adults. Findings were gender-specific, with MBI affecting more men than women. Knowing the estimates of these symptoms in the population is essential for understanding and differentiating the very early development of clinical disorders.

Mild behavioral impairment (MBI) describes later life acquired, sustained neuropsychiatric symptoms (NPS) in cognitively normal individuals or those with mild cognitive impairment (MCI), as an at-risk state for incident cognitive decline and dementia. We developed an operational definition of MBI and tested whether the presence of MBI was related to caregiver burden in patients with subjective cognitive decline (SCD) or MCI assessed at a memory clinic.

MBI was assessed in 282 consecutive memory clinic patients with SCD (n = 119) or MCI (n = 163) in accordance with the International Society to Advance Alzheimer's Research and Treatment – Alzheimer's Association (ISTAART–AA) research diagnostic criteria. We operationalized a definition of MBI using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Caregiver burden was assessed using the Zarit caregiver burden scale. Generalized linear regression was used to model the effect of MBI domains on caregiver burden.

While MBI was more prevalent in MCI (85.3%) than in SCD (76.5%), this difference was not statistically significant (p = 0.06). Prevalence estimates across MBI domains were affective dysregulation (77.8%); impulse control (64.4%); decreased motivation (51.7%); social inappropriateness (27.8%); and abnormal perception or thought content (8.7%). Affective dysregulation (p = 0.03) and decreased motivation (p=0.01) were more prevalent in MCI than SCD patients. Caregiver burden was 3.35 times higher when MBI was present after controlling for age, education, sex, and MCI (p < 0.0001).

MBI was common in memory clinic patients without dementia and was associated with greater caregiver burden. These data show that MBI is a common and clinically relevant syndrome.

Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons.

We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB−) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex.

Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00–1.06) and BAI (OR = 1.04; 1.01–1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83–2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET− group but the difference was not significant (OR = 1.77; 0.97–3.22).

As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.

We apply recently recommended Parkinson's disease mild cognitive impairment (PD-MCI) classification criteria from the movement disorders society (MDS) to PD patients and controls and compare diagnoses to that of short global cognitive scales at baseline and over time. We also examine baseline prevalence of neuropsychiatric symptoms across different definitions of MCI.

51 PD patients and 50 controls were classified as cognitively normal, MCI, or demented using MDS criteria (1.5 or 2.0 SD below normative values), Clinical Dementia Rating Scale (CDR), and the Dementia Rating Scale (DRS). All subject had parallel assessment with the Neuropsychiatric inventory (NPI).

We confirmed that PD-MCI (a) is frequent, (b) increases the risk of PDD, and (c) affects multiple cognitive domains. We highlight the predictive variability of different criteria, suggesting the need for further refinement and standardization. When a common dementia outcome was used, the Level II MDS optimal testing battery with impairment defined as two SD below norms in 2+ tests performs the best. Neuropsychiatric symptoms were more common in PD across all baseline and longitudinal cognitive classifications.

Our results advance previous findings on the utility of MDS PD-MCI criteria for PD patients and controls at baseline and over time. Additionally, we emphasize the possible utility of other cognitive scales and neuropsychiatric symptoms.

To investigate the differential associations between sensory loss and neuropsychiatric symptoms among older adults with and without diagnosed neurocognitive disorder.

The sample comprised 1,393 adults (52.3% men) aged between 72 and 79 years from a community-based cohort study. There were 213 cases of mild and 64 cases of major neurocognitive disorders. The main outcome was number of informant reported symptoms on the Neuropsychiatric Inventory (NPI). Sensory loss was defined by visual acuity worse the 0.3 logMAR (6/12 or 20/40) and self-reported hearing problems.

Clinically relevant NPI symptoms were reported in 182 (13.1%) participants, but no individual symptom occurred in more than 5% of the total sample. Among participants diagnosed with a major neurocognitive disorder, those with any sensory loss had over three times (95%CI: 1.72–11.78) greater rates of NPI symptoms than those with unimpaired levels of sensory functioning. There were no differences in the number of neuropsychiatric symptoms by type of sensory loss, and no additional risk associated with a dual sensory loss compared to a single sensory loss. There was no evidence of an association between sensory loss and number of neuropsychiatric symptoms among cognitively healthy adults.

The extent to which this association is the result of underlying neuropathology, unmet need, or interpersonal factors is unclear. These findings have significant implications for dementia care settings, including hospitals and respite care, as patients with sensory loss are at increased risk of neuropsychiatric symptoms and may require additional psychosocial support. Interventions to manage sensory loss and reduce the impact of sensory limitations on neuropsychiatric symptoms are needed.