The International Psychogeriatric Association (IPA) published a provisional consensus definition of agitation in cognitive disorders in 2015. As proposed by the original work group, we summarize the use and validation of criteria in order to remove “provisional” from the definition.

This report summarizes information from the academic literature, research resources, clinical guidelines, expert surveys, and patient and family advocates on the experience of use of the IPA definition. The information was reviewed by a working group of topic experts to create a finalized definition.

We present a final definition which closely resembles the provisional definition with modifications to address special circumstances. We also summarize the development of tools for diagnosis and assessment of agitation and propose strategies for dissemination and integration into precision diagnosis and agitation interventions.

The IPA definition of agitation captures a common and important entity that is recognized by many stakeholders. Dissemination of the definition will permit broader detection and can advance research and best practices for care of patients with agitation.

To develop an agitation reduction and prevention algorithm is intended to guide implementation of the definition of agitation developed by the International Psychogeriatric Association (IPA)

Review of literature on treatment guidelines and recommended algorithms; algorithm development through reiterative integration of research information and expert opinion

IPA Agitation Workgroup

IPA panel of international experts on agitation

Integration of available information into a comprehensive algorithm

None

The IPA Agitation Work Group recommends the Investigate, Plan, and Act (IPA) approach to agitation reduction and prevention. A thorough investigation of the behavior is followed by planning and acting with an emphasis on shared decision-making; the success of the plan is evaluated and adjusted as needed. The process is repeated until agitation is reduced to an acceptable level and prevention of recurrence is optimized. Psychosocial interventions are part of every plan and are continued throughout the process. Pharmacologic interventions are organized into panels of choices for nocturnal/circadian agitation; mild-moderate agitation or agitation with prominent mood features; moderate-severe agitation; and severe agitation with threatened harm to the patient or others. Therapeutic alternatives are presented for each panel. The occurrence of agitation in a variety of venues—home, nursing home, emergency department, hospice—and adjustments to the therapeutic approach are presented.

The IPA definition of agitation is operationalized into an agitation management algorithm that emphasizes the integration of psychosocial and pharmacologic interventions, reiterative assessment of response to treatment, adjustment of therapeutic approaches to reflect the clinical situation, and shared decision-making.

To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study.

Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed.

Community-based multi-centered study based in Toronto across 5 academic sites.

Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls.

We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores.

A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD.

This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.

Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation.

To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer’s disease (AD).

Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta–gamma coupling were assessed at the same time points using the N-back task and EEG.

There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta–gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta–gamma coupling.

This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586)

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.

Lacunar stroke is a small (<2 cm) infarction that accounts for approximately 20% of all strokes. While a third of all stroke patients experience depressive symptoms, the prevalence of depression in the lacunar stroke patient population is unclear. This meta-analysis aimed to synthesize the evidence on the effect of lacunar stroke and deep white matter disease on depressive symptoms.

A systematic search of electronic databases was conducted, resulting in the inclusion of 12 studies. Analyses were performed on the effects of lacunar stroke, volume and location of lacunes on depression prevalence, and the effect on depression severity. The effects estimates were calculated in random-effects models.

None of the analyses produced statistically significant results. Lacunar stroke patients had a non-significantly higher prevalence of depression compared to patients with non-lacunar cerebrovascular diseases (OR = 1.46, 95% CI: 0.88–2.43, p = 0.15). Neither thalamic (OR = 1.37 (0.85–2.20), p = 0.19), deep white matter (RR = 1.16 (0.85–1.57), p = 0.35), multiple lacunes (OR = 1.34 (0.81–2.22), p = 0.25), or the volume of lacunes (MD = −4.71 (−351.59–342.18), p = 0.98) had an effect on depression prevalence. Lastly, lacunar stroke did not influence depressive symptom severity (MD = 0.96 (−1.57–3.48), p = 0.46).

The pooled group of patients with lacunar stroke and deep white matter disease appear to have a similar prevalence of depression compared to those with other types of cerebrovascular diseases. However, the small number of studies, heterogeneous comparison groups, and high statistical heterogeneity between studies posed an obstacle to the meta-analysis. To determine appropriate screening and treatment approaches, future research will need to separate lacunar stroke and deep white matter disease patients, and include larger sample sizes and healthy control groups to determine their distinct contributions to depression.

Dementia affects 15% of Canadians 65 and older, and the prevalence is expected to double over the next two decades. Low socioeconomic status (SES) can increase the risk of Alzheimer's disease (AD) and the precursor mild cognitive impairment (MCI), but it is unknown what the relationship of SES is on initial clinical presentation to a memory disorders clinic.

Data from 127 AD and 135 MCI patients who presented to our Memory Disorders Clinic from 2004 to 2013 were analyzed retrospectively. We examined the relationship between SES (measured using Hollingshead two-factor index) and (1) diagnosis of either AD or MCI; (2) age when first presented to clinic; (3) objective cognitive tests to indicate clinical severity; and (4) the use of cognitive enhancers, medication for treating mild-to-moderate AD patients.

AD patients had lower SES than MCI patients (p < 0.001, r = 0.232). Lower SES was associated with a greater age at initial time of diagnosis (χ2 = 11.5, p = 0.001). In MCI patients, higher SES individuals outperformed lower SES individuals on the BNA after correcting for the effect of age (p = 0.004). Lower SES was also associated with decreased use of cognitive enhancers in AD patients (p < 0.001, r = 0.842).

Individuals with lower SES come into memory clinic later when the disease has progressed to dementia, while higher SES individuals present earlier when the disease is still in its MCI stage. There were more higher SES individuals who presented to our memory clinic. Higher SES is associated with better cognitive functioning and increased use of cognitive enhancers. The health policy implication is that we need to better engage economically disadvantaged individuals, perhaps at the primary care level.