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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.