Corinne E. Fischer

Neurocognitive profiles in older adults with and without major depression

To delineate the differences between older persons with and without a diagnosis of major depression.

Neurobiology of Delusions in Alzheimer’s Disease

Alzheimer’s disease (AD) is associated with cognitive and functional impairment as well as neuropsychiatric sequelae, including psychotic symptoms such as delusions and hallucinations. Strong evidence supports the need to study delusions separate from hallucinations. Integrating the epidemiology, clinical correlates, and neuropathological and genetic literature for delusions in AD allows us to speculate on etiology and mechanisms. Plaque and tangle deposition in individuals with susceptible alleles of serotonergic, muscarinic, nicotinic, or Apoε4 genes appears to result in disruption of cortical circuitry, culminating in delusions. While delusions in AD correspond to a phenotype distinct from AD without delusions, subtypes of delusions may also define further distinct clinical entities. Persecutory delusions may occur earlier in the illness and have a more significant genetic component than misidentification delusions, which are associated with increased cognitive impairment and advanced dementia. Clearly distinguishing between these two syndromes is essential to making progress in the area of delusions in AD.

Musical and auditory hallucinations: A spectrum.

Abstract  Musical hallucinosis is a rare and poorly understood clinical phenomenon. While an association appears to exist between this phenomenon and organic brain pathology, aging and sensory impairment the precise association remains unclear. The authors present two cases of musical hallucinosis, both in elderly patients with mild–moderate cognitive impairment and mild–moderate hearing loss, who subsequently developed auditory hallucinations and in one case command hallucinations. The literature in reference to musical hallucinosis will be reviewed and a theory relating to the development of musical hallucinations will be proposed.

Prevalence of Depression in Patients With Mild Cognitive Impairment: A Systematic Review and Meta-analysis

Importance Depression is common in individuals with mild cognitive impairment (MCI) and may confer a higher likelihood of progression to dementia. Prevalence estimates of depression in those with MCI are required to guide both clinical decisions and public health policy, but published results are variable and lack precision. Objective To provide a precise estimate of the prevalence of depression in individuals with MCI and identify reasons for heterogeneity in the reported results. Data Sources A search of literature from database inception to March 2016 was performed using Medline, Embase, and PsycINFO. Hand searching of all included articles was performed, including a Google Scholar search of citations of included articles. Study Selection Articles were included if they (1) were published in English, (2) reported patients with MCI as a primary study group, (3) reported depression or depressive symptoms using a validated instrument, and (4) reported the prevalence of depression in patients with MCI. Data Extraction and Synthesis All abstracts, full-text articles, and other sources were reviewed, with data extracted in duplicate. The overall prevalence of depression in patients with MCI was pooled using a random-effects model. Heterogeneity was explored using stratification and random-effects meta-regression. Main Outcomes and Measures The prevalence of depression in patients with MCI, reported as a percentage with 95% CIs. Estimates were also stratified by population source (community-based or clinic-based sample), method of depression diagnosis (clinician-administered, informant-based, or self-report), and method of MCI diagnosis (cognitive vs global measure and amnestic vs nonamnestic). Results Of 5687 unique abstracts, 255 were selected for full-text review, and 57 studies, representing 20 892 patients, met all inclusion criteria. The overall pooled prevalence of depression in patients with MCI was 32% (95% CI, 27-37), with significant heterogeneity between estimates (I2 = 90.7%). When stratified by source, the prevalence of depression in patients with MCI in community-based samples was 25% (95% CI, 19-30) and was 40% (95% CI, 32-48) in clinic-based samples, which was significantly different (P < .001). The method used to diagnose depression did not significantly influence the prevalence estimate, nor did the criteria used for MCI diagnosis or MCI subtype. Conclusions and Relevance The prevalence of depression in patients with MCI is high. A contributor to heterogeneity in the reported literature is the source of the sample, with greater depression burden prevalent in clinic-based samples.

The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia Populations.

BACKGROUND Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimers Research and Treatment - Alzheimers Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described. OBJECTIVE To develop an instrument based on ISTAART-AA MBI criteria. METHODS Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults. RESULTS We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician. CONCLUSION The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes.

A systematic review and meta-analysis of on-road simulator and cognitive driving assessment in Alzheimer's disease and mild cognitive impairment

BACKGROUND Many individuals with Alzheimers disease (AD) and mild cognitive impairment (MCI) are at an increased risk of driving impairment. There is a need for tools with sufficient validity to help clinicians assess driving ability. OBJECTIVE Provide a systematic review and meta-analysis of the primary driving assessment methods (on-road, cognitive, driving simulation assessments) in patients with MCI and AD. METHODS We investigated (1) the predictive utility of cognitive tests and domains, and (2) the areas and degree of driving impairment in patients with MCI and AD. Effect sizes were derived and analyzed in a random effects model. RESULTS Thirty-two articles (including 1,293 AD patients, 92 MCI patients, 2,040 healthy older controls) met inclusion criteria. Driving outcomes included: On-road test scores, pass/fail classifications, errors; caregiver reports; real world crash involvement; and driving simulator collisions/risky behavior. Executive function (ES [95% CI]; 0.61 [0.41, 0.81]), attention (0.55 [0.33, 0.77]), visuospatial function (0.50 [0.34, 0.65]), and global cognition (0.61 [0.39, 0.83]) emerged as significant predictors of driving performance. Trail Making Test Part B (TMT-B, 0.61 [0.28, 0.94]), TMT-A (0.65 [0.08, 1.21]), and Maze test (0.88 [0.60, 1.15]) emerged as the best single predictors of driving performance. Patients with very mild AD (CDR = 0.5) mild AD (CDR = 1) were more likely to fail an on-road test than healthy control drivers (CDR = 0), with failure rates of 13.6%, 33.3% and 1.6%, respectively. CONCLUSION The driving ability of patients with MCI and AD appears to be related to degree of cognitive impairment. Across studies, there are inconsistent cognitive predictors and reported driving outcomes in MCI and AD patients. Future large-scale studies should investigate the driving performance and associated neural networks of subgroups of AD (very mild, mild, moderate) and MCI (amnestic, non-amnestic, single-domain, multiple-domain).

What Characterizes Late-Life Depression?

This article analyzes late-life depression, looking carefully at what defines a person as elderly, the incidence of late-life depression, complications and differences in symptoms between young and old patients with depression, subsyndromal depression, bipolar depression in the elderly, the relationship between grief and depression, along with sleep disturbances and suicidal ideation.

Delusions Increase Functional Impairment in Alzheimer’s Disease

Background/Aims: Delusions in Alzheimer’s disease (AD) may be associated with functional impairment. No studies to date have used functional instruments sensitive to changes in frontal executive function, possibly underestimating the impact. Methods: Patients with AD with and without delusions were administered cognitive tests and questionnaires to assess depression and quality of life. Caregivers were administered questionnaires to assess functional impairment, caregiver burden and behavioural symptoms. Results: AD patients with delusions (n = 19) when compared to AD patients without delusions (n = 19) matched for age, education and global cognitive function were significantly more functionally impaired based on performance on the Disability Assessment for Dementia Scale (p < 0.005). Conclusion: AD patients with delusions have significantly worse functional performance.

Grey matter atrophy in mild cognitive impairment / early Alzheimer disease associated with delusions: a voxel-based morphometry study.

OBJECTIVES Grey matter atrophy in the right hemisphere has been shown to be more severe in dementia patients with delusions, suggesting a neuroanatomical localization that may be pertinent to impending neurodegeneration. Delusional symptoms may arise when atrophy in these areas reduces the regulatory functions of the right hemisphere, in tandem with asymmetric neuropathology in the left hemisphere. We hypothesized that delusional patients with either amnestic mild cognitive impairment (MCI) or early Alzheimer Disease (AD) would experience more pronounced grey matter atrophy in the right frontal lobe compared with matched patients without delusions. METHODS We used neuroimaging and clinical data obtained from the Alzheimers Disease Neuroimaging Initiative. A comparison group of twenty-nine nondelusional MCI/early AD participants were compared with twenty-nine delusional participants using voxel-based morphometry, matched at baseline by age, sex, education, and Mini-Mental State Exam score. All included participants were diagnosed with amnestic MCI at study baseline. RESULTS Fifteen voxel clusters of decreased grey matter in participants with delusions were detected. Prominent grey matter decrease was observed in the right precentral gyrus, right inferior frontal gyrus, right insula, and left middle occipital gyrus, areas that may be involved in control of thought and emotions. CONCLUSION Greater right fronto-temporal grey matter atrophy was observed in MCI or early AD participants with delusions compared to matched patients without delusions. Consistent with our predictions, asymmetric grey matter atrophy in the right hemisphere may contribute to development of delusions through loss of executive inhibition.

Impact of socioeconomic status on initial clinical presentation to a memory disorders clinic.

BACKGROUND 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 Alzheimers 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. METHODS 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. RESULTS 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). CONCLUSION 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.