Elizabeth Crocco

Stability of Different Subtypes of Mild Cognitive Impairment among the Elderly over a 2- to 3-Year Follow-Up Period

Background/Aims: To investigate the longitudinal stability and progression of different subtypes of mild cognitive impairment (MCI) in older adults. Methods: We classified 217 individuals with no cognitive impairment (NCI), amnestic MCI (aMCI) based on a single test (aMCI-1) or multiple tests (aMCI-2+), nonamnestic MCI (naMCI) based on a single test (naMCI-1) or multiple tests (naMCI-2+), or amnestic + nonamnestic MCI (a+naMCI), using their baseline neuropsychological test scores, and performed annual follow-up evaluations for up to 3 years. Results: None of the subjects with aMCI-2+ reverted to normal during follow-up, with 50% of these subjects remaining stable and 50% worsening over time. Similarly, less than 20% of subjects with aMCI-2+ and a+naMCI reverted to NCI during the follow-up period, whereas 50% of aMCI-1 and 37% with naMCI-1 reverted to NCI during this same period. Conclusion: Reversion to NCI occurs much more frequently when the diagnosis of MCI is based on the results of a single neuropsychological test than when it is based on the results of more memory tests. In epidemiological studies and clinical trials the diagnosis of MCI will likely be more stable if impairment on more than one test is required for amnestic and/or nonamnestic domains.

Cognitive profiles in Alzheimer's disease and in mild cognitive impairment of different etiologies.

There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer’s disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed.

Repeat expansions in the C9ORF72 gene contribute to Alzheimer's disease in Caucasians

Recently, a hexanucleotide repeat expansion in the C9ORF72 gene has been identified to account for a significant portion of Caucasian families affected by frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Given the clinical overlap of FTD with Alzheimers disease (AD), we hypothesized that C9ORF72 expansions might contribute to AD. In Caucasians, we found C9ORF72 expansions in the pathogenic range of FTD/ALS (>30 repeats) at a proportion of 0.76% in AD cases versus 0 in control subjects (p = 3.3E-03; 1182 cases, 1039 controls). In contrast, no large expansions were detected in individuals of African American ethnicity (291 cases, 620 controls). However, in the range of normal variation of C9ORF72 expansions (0-23 repeat copies), we detected significant differences in distribution and mean repeat counts between Caucasians and African Americans. Clinical and pathological re-evaluation of identified C9ORF72 expansion carriers revealed 9 clinical and/or autopsy confirmed AD and 2 FTD final diagnoses. Thus, our results support the notion that large C9ORF72 expansions lead to a phenotypic spectrum of neurodegenerative disease including AD.

How Late-Life Depression Affects Cognition: Neural Mechanisms

Late-life depression is a major health problem and a significant cause of dysfunction that warrants closer evaluation and study. In contrast to younger depressed patients, most depressed older adults suffer more severe variants of the disorder, including significant cognitive impairments. These cognitive changes add to the severity of symptoms and disability that older depressed patients face and likely reflect compromise of certain neural circuits, linking cognitive impairment to late-life depression. Studies examining clinical correlates, neuropsychological testing, and functional and anatomic imaging have yielded a clearer understanding of the neural mechanisms underlying cognitive deficits in late-life depression. This article discusses cognitive impairment in geriatric depression and how developing a better understanding of its neural correlates may lead to improved understanding and outcome of this specific disorder.

Factors related to medication adherence in memory disorder clinic patients

Medication adherence is a substantial problem in the elderly. It may be even more important among elderly persons with memory problems, since other factors that lead to non-adherence may be compounded with the memory problems themselves. The objective was to determine whether a model that integrates research on medication adherence from several research domains is useful in understanding adherence in elderly patients. The methodology involved a cross-sectional observational study using a convenience sample of 63 patients drawn from a university-affiliated outpatient memory disorders clinic. The primary measure of medication adherence was caregivers’ reports of patients’ medication adherence. Patients and their caregivers were asked questions assessing their beliefs about the seriousness of each condition for which a medication was prescribed and the likely outcome of that condition without treatment. Additional data collected included presence of side effects, total number of medications taken, and patients’ mood and cognitive status. Multilevel path analysis confirmed several model-based predictions. Caregivers’ reports of adherence were predicted by estimates of disease outcome, the presence of side effects, and patients’ relying on themselves to remember to take medications. Results partially confirm the integrative model in understanding medication adherence in these patients. Patients’ beliefs about the likely effect of medication treatment for their condition and the presence of side effects influence reported medication adherence. Results thus suggest that efforts to educate patients about the likely response of their medical condition to treatment and to assess and deal with medication side effects might improve patient adherence.

A New Scale for the Evaluation of Proactive and Retroactive Interference in Mild Cognitive Impairment and Early Alzheimer’s Disease

Objective: The authors evaluated the psychometric properties and clinical utility of the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), in patients with amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer’s disease (AD). Methods: Subjects were administered Target List A and instructed to remember 15 common words belonging to a specific semantic category, using multi-modal, active encoding procedures. After free recall and cued recall trials of the target list, a second learning trial was offered, followed by a cued recall trial, to facilitate the initial acquisition of targets. Thereafter, the subject was exposed to a semantically-related List B, which was administered in the same manner as Target List A. Test-retest reliability, concurrent and discriminative validity were assessed. LASSI-L measures were then correlated with Magnetic Resonance Imaging (MRI) measurements of medial temporal lobe atrophy (MTA). Results: High test-retest, concurrent and discriminative validity was obtained for LASSI-L subscales, and MTA atrophy scores were highly and negatively correlated with LASSI-L indices. Conclusion: Subtests of the LASSI-L demonstrate high reliability and validity, and are strongly associated with MRI biomarkers of early neurodegenerative disease. It is concluded that the LASSI-L is a highly promising test for the assessment of mild cognitive impairment and early AD among the elderly.

APOE ε4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease

Pathogenesis of Alzheimers disease (AD) in apolipoprotein E ε4 (APOE ε4) carriers remains unclear. We hypothesize that APOE isoforms have differential effects on synaptic function.

Pharmacological Management of Anxiety Disorders in the Elderly

Opinion statementAnxiety disorders are common in the elderly. Additionally, anxiety symptoms often accompany comorbid psychiatric, medical, as well as neurodegenerative diseases in the older population. Anxiety in the elderly, often accompanied by depression, can lead to worsening physical, cognitive, and functional impairments in this vulnerable population. Antidepressants are considered first-line treatment. Both selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are efficacious and well-tolerated in the elderly. Some SSRIs are strong inhibitors of the cytochrome P450 hepatic pathway whereas others have less potential for drug interaction. Those antidepressants with more favorable pharmacokinetic profiles should be considered first-line in the treatment of anxiety. Mirtazapine and vortioxetine are also considered safe treatment options. Buspirone may have a benefit, but lacks studies in elderly populations. Although tricyclic/tetracyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) may be effective in the elderly, their side effect and safety profiles are suboptimal and thus are not recommended in late-life. Benzodiazepines and beta-blockers should generally be avoided when treating anxiety in the elderly. There is not enough evidence to support the use of antipsychotics or mood stabilizers given their risk of problems in both the long- and short-term. In addition, antipsychotics have a black box warning for increased mortality in elderly patients with dementia.

A novel cognitive assessment paradigm to detect Pre-mild cognitive impairment (PreMCI) and the relationship to biological markers of Alzheimer's disease

OBJECTIVE A number of older adults obtain normal scores on formal cognitive tests, but present clinical concerns that raise suspicion of cognitive decline. Despite not meeting full criteria for Mild Cognitive Impairment (MCI), these PreMCI states confer risk for progression to Alzheimers disease (AD). This investigation addressed a pressing need to identify cognitive measures that are sensitive to PreMCI and are associated with brain biomarkers of neurodegeneration. METHOD Participants included 49 older adults with a clinical history suggestive of cognitive decline but normal scores on an array of neuropsychological measures, thus not meeting formal criteria for MCI. The performance of these PreMCI participants were compared to 117 cognitively normal (CN) elders on the LASSI-L, a cognitive stress test that uniquely assesses the failure to recover from proactive semantic interference effects (frPSI). Finally, a subset of these individuals had volumetric analyses based on MRI scans. RESULTS PreMCI participants evidenced greater LASSI- L deficits, particularly with regards to frPSI and delayed recall, relative to the CN group. No differences on MRI measures were observed. Controlling for false discovery rate (FDR), frPSI was uniquely related to increased dilatation of the inferior lateral ventricle and decreased MRI volumes in the hippocampus, precuneus, superior parietal region, and other AD prone areas. In contrast, other LASSI-L indices and standard memory tests were not related to volumetric findings. CONCLUSIONS Despite equivalent performance on traditional memory measures, the frPSI distinguished between PreMCI and CN elders and was associated with reductions in brain volume in numerous AD-relevant brain regions.

A Novel Method for Direct Assessment of Everyday Competence Among Older Adults

BACKGROUND Recent findings indicate that impairments in functional performance do occur among individuals diagnosed with mild cognitive impairment (MCI). Most assessment strategies for everyday competence are associated with challenges with reliability, are typically in paper and pencil format, or require in-person administration by a trained professional. OBJECTIVE This paper reports on a novel technology-based assessment battery of everyday competence that includes ecologically valid simulations of daily activities important to independence. METHODS The sample included 85 non-cognitively impaired older adults aged 65+ and 62 older adults diagnosed with amnestic MCI (aMCI). Participants completed standard measures of cognitive abilities and the computerized battery of everyday tasks, which included simulations of a doctors visit; and medication and financial management tasks. RESULTS The older adults with aMCI performed significantly poorer on all three tasks in the everyday task battery. Performance on these measures were also moderately correlated with standard measures of cognitive abilities and showed good test-retest reliability. CONCLUSIONS The results show that it is feasible to use a technology-based assessment battery of everyday tasks with both non-cognitively impaired older adults and older adults with MCI. The use of this type of battery can overcome many of the logistic constraints associated with current functional assessment protocols.