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Making sense of mild cognitive impairment: a qualitative exploration of the patient's experience.

PURPOSE: The proposed dementia precursor state of mild cognitive impairment is emerging as a primary target of aging research. Yet, little is known about the subjective experience of living with a diagnosis of mild cognitive impairment. This study examines, from the patient's perspective, the experience of living with and making sense of the diagnosis. DESIGN AND METHODS: We recruited 12 older adults with amnestic or nonamnestic mild cognitive impairment from a university-based memory disorders clinic. We conducted in-home, semistructured interviews in order to elicit rich descriptions of the personal experience of having mild cognitive impairment. We used the qualitative method of grounded theory to analyze narrative data. RESULTS: Understanding and coming to terms with the syndrome, or assigning meaning, constituted a fundamental aspect of living with a diagnosis of mild cognitive impairment. This process comprised interrelated emotional and cognitive dimensions. Participants employed a range of positive, neutral, and negative phrasing in order to depict their emotional reactions to receiving a diagnosis. Cognitive representations of mild cognitive impairment included both prognosis-focused and face-value appraisals. Expectations of normal aging, personal experience with dementia, and concurrent health problems were key contextual factors that provided the backdrop against which participants assigned meaning to a diagnosis of mild cognitive impairment. IMPLICATIONS: Clinicians who disclose diagnoses of mild cognitive impairment need to be mindful of the potential for varying interpretations of the information that is conveyed. Future research needs to include systematic, longitudinal investigations of illness representation and its impact on health behaviors among individuals with mild cognitive impairment.

Aged↗

Visual and verbal short-term memory deficits in childhood leukemia survivors after intrathecal chemotherapy.

Assessed survivors of childhood lymphoblastic leukemia (ALL) treated with intrathecal chemotherapy, using the Wide Range Assessment of Memory and Learning (WRAML), compared to controls without cancer, matched as closely as possible in age, SES, and gender. Mild, but consistent, deficits were found in both visual-spatial and verbal single-trial memory tasks. In multitrial learning, only visual-spatial tasks resulted in deficient scores, while verbal learning was within the normal range. IQ results indicated scores 10-20 points lower in the ALL group. Memory results are related to deficits in strategic planning and attentional distractiveness. The WRAML may be a useful clinical tool to evaluate differential memory deficits in children with ALL.

Adolescent↗

Brief report: effect of intravenous methotrexate dose and infusion rate on neuropsychological function one year after diagnosis of acute lymphoblastic leukemia.

OBJECTIVE: To compare the effects of two intravenous (IV) methotrexate (MTX) infusion protocols on cognitive function in children newly diagnosed with acute lymphoblastic leukemia (ALL). METHODS: We compared 19 children treated with 1 g/m(2) of IV MTX over 24 hr (Group 1) to 13 children treated with 2 g/m(2) of IV MTX over 4 hr (Group 2) on measures of working memory, nonverbal, and verbal skills shortly after diagnosis (Time 1) and 1 year later (Time 2). RESULTS: A significant GroupxTime interaction was found for a composite measure of working memory with Group 2 declining from Time 1 to Time 2. Group 2 performed significantly worse than Group 1 on a composite measure of nonverbal skills at both time points. CONCLUSIONS: Findings suggest that difficulties in working memory and nonverbal skills may be evident during the first year of treatment for ALL and that severity may be dependent on IV MTX dose and/or infusion rate.

Antimetabolites, Antineoplastic↗

Executive memory dysfunctions following mild traumatic brain injury.

OBJECTIVES: To explore the contribution of executive dysfunctions to mnemonic problems in adults with mild traumatic brain injury (MTBI). DESIGN: Prospective quasiexperimental between-groups design. PARTICIPANTS: Ninety-nine persons with MTBI were compared to 90 control group participants matched for gender, age, and education. SETTING: Two Canadian brain injury rehabilitation programs. MAIN OUTCOME MEASURE: California Verbal Learning Test. RESULTS: Participants with MTBI showed a significant deficit in free recall on the California Verbal Learning Test but performed similarly to the comparison group on the recognition task. Furthermore, the participants with MTBI were less likely to use semantic clustering as a memorizing strategy and made more intrusion errors and false-positive errors on the recognition task. CONCLUSIONS: While the scores for the participants with MTBI are only slightly lower than the norm, they demonstrate that MTBI has a negative effect on mnemonic performance. The results are explained in terms of a deficit in registration/retrieval processes rather than a malfunction of the storage processes. This supports the initial hypothesis that executive dysfunctions are detrimental to the quality of mnemonic functions in patients with MTBI.

Adolescent↗

The effect of chronic alcohol treatment on the radial maze performance of rats.

The effect of chronic alcohol drinking on maze behaviour was studied in laboratory rats. Thirteen animals received 20% alcohol for 15 weeks ad libitum, and 18 were kept under identical conditions drinking tap water. Both groups were then tested twice within one day for performance in an 8 arm radial maze after 48 h fluid deprivation. Reinforcing fluid droplets were placed at the end of each arm only at the beginning of the test. Total and erroneous entries to the arms, total time spent until reaching the criterion, and strategy of arm choice was recorded for each animal. Activity of the groups did not differ significantly, nor were differences in choosing strategy found. Alcoholic rats, however, showed a significant loss of performance in the second test: they frequently entered arms already visited, and in a number of cases were unable to complete the test within time. These and earlier findings suggest no impairment of learning ability or short term memory, but rather some kind of rigidity and invariability of behaviour.

Alcoholism↗

5-HT4 receptor stimulation facilitates acetylcholine release in rat frontal cortex.

The effect of the serotonergic 5-HT4 receptor agonists BIMU 1 and BIMU 8 on in vivo acetylcholine (ACh) release in brain hemispheric regions of freely moving rats was investigated using the microdialysis technique. Both agonists, applied intracerebroventricularly, facilitated the release of ACh selectively in the frontal cortex and were ineffective in the striatum or dorsal hippocampus. The facilitatory effect of BIMU 1 in frontal cortex was prevented by the selective 5-HT4 receptor antagonists GR 125487 and GR 113808 which by themselves did not alter basal release. the results provide the first evidence that serotonin facilitates ACh release in frontal cortex through stimulation of 5-HT4 receptors which are not tonically activated. 5-HT4 receptor agonists might thus offer a novel means of boosting central cholinergic function to overcome the cholinergic deficit in memory disorders.

Acetylcholine↗

Working memory failure by stimulation of hippocampal adenosine A1 receptors in rats.

THE highly selective adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA) significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterally at 0.3 and 1.0 microgram per side into the dorsal hippocampus. Pretreatment with the selective adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 1 mg kg-1, i.p.) prevented the increase in working memory errors induced by intrahippocampal administration of CHA (1.0 microgram per side). CGS-21680, a highly selective agonist for adenosine A2 receptors, had no effect on the number of working memory errors, when administered intrahippocampally at a dose of 1.0 microgram per side. These results suggest that activation of hippocampal adenosine A1 receptors interferes with neural processes involved in working memory function.

Adenosine↗

Short-term memory for colour following posterior hemispheric lesions in man.

Short-term memory for colour was studied in five patients with circumscribed posterior hemispheric lesions. It was impaired independently of colour discrimination in one and more than colour discrimination in two patients. Two patients were normal in colour short-term memory, one with normal and one with deficient colour discrimination performance. Deficient performance in colour short-term memory was associated with bilateral lesions of the inferior occipitotemporal junction including the lateral part of the fusiform gyrus or with a unilateral lesion of the left parieto-occipital convexity. An additional colour constancy deficit was found in the former but not the latter condition. Thus, colour short-term memory can be affected independently of colour discrimination or colour constancy, and may depend on at least two distinct neural circuits.

Adult↗

Impaired P600 in neuroleptic naive patients with first-episode schizophrenia.

Deficits of working memory (WM) are recognized as an important pathological feature in schizophrenia. Since the P600 component of event related potentials has been hypothesized that represents aspects of second-pass parsing processes of information processing, and is related to WM, the present study focuses on P600 elicited during a WM test in drug-naive first-episode schizophrenics (FES) compared to healthy controls. We examined 16 drug-naive first-episode schizophrenic patients and 23 healthy controls matched for age and sex. Compared with controls schizophrenic patients showed reduced P600 amplitude on left temporoparietal region and increased P600 amplitude on left occipital region. With regard to the latency, the patients exhibited significantly prolongation on right temporoparietal region. The obtained pattern of differences classified correctly 89.20% of patients. Memory performance of patients was also significantly impaired relative to controls. Our results suggest that second-pass parsing process of information processing, as indexed by P600, elicited during a WM test, is impaired in FES. Moreover, these findings lend support to the view that the auditory WM in schizophrenia involves or affects a circuitry including temporoparietal and occipital brain areas.

Acoustic Stimulation↗

Endomorphin-1 improves scopolamine-induced impairment of short-term memory via mu1-opioid receptor in mice.

The effects of intracerebroventricular injection of endomorphin-1 and 2, endogenous mu-opioid receptor agonists, on the scopolamine-induced impairment of spontaneous alternation performance associated with short-term memory were investigated in mice. Endomorphin-1 (0.03 microg) inhibited scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting total arm entries, while endomorphin-2 (0.01-10 microg) failed to significantly influence the scopolamine (1 mg/kg)-induced impairment. Endomorphin-1 (0.03 microg) itself had no marked effects on spontaneous alternation performance in intact mice. Although beta-funaltrexamine (5 microg), a mu-opioid receptor antagonist, did not significantly affect the inhibitory effects of endomorphin-1 (0.03 microg) on the scopolamine (1 mg/kg)-induced impairment, naloxonazine (35 mg/kg), a mu1-opioid receptor antagonist, significantly reversed the inhibitory effects of endomorphin-1 (0.03 microg) on the impairment. Naloxonazine (35 mg/kg) unlike beta-funaltrexamine (5 microg) did not significantly influence the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. These results suggest that endomorphin-1 improves the disturbance of short-term memory resulting from cholinergic dysfunction through the mediation of mu1-opioid receptors.

Analgesics, Opioid↗

Psychological morbidity in caregivers is associated with depression in patients with dementia.

The relationship between psychological morbidity in caregivers and depression in patients with dementia was examined using data collected on 193 patient-caregiver dyads attending a memory disorders clinic. Caregivers had high rates and levels of psychological morbidity which were associated with the severity of dementia (but neither the type nor duration), with the caregiver being a spouse and female and living with the person with dementia. A logistic regression analysis identified clinician-rated patient depression score and demanding problem behaviors as being independently and significantly associated with caregiver psychological morbidity. This new finding of a link between patient depression and caregiver psychological morbidity has implications for more focused treatment programs for both caregivers and patients.

Activities of Daily Living↗

Depressive symptomatology in first-degree family caregivers of Alzheimer disease patients: a cross-ethnic comparison.

This study investigated the prevalence of depressive symptoms among White Hispanic (WH) and White non-Hispanic (WNH) first-degree family caregivers. We screened 653 primary caregivers of family members with possible or probable Alzheimer disease who presented at our outpatient memory disorders clinic. Caregiver depression was assessed utilizing the Center for Epidemiologic Studies-Depression (CES-D) Scale. Overall, depression (CES-D scores > or = 16) was more common among WH (45%) than among WNH (36%) caregivers (p < 0.05). Elevated CES-D scores among the entire caregiving sample were also linked with being a female spouse (p=0.002), increased level of patient cognitive impairment (p=0.002), and patient psychosis (p=0.002). Risk factors for caregiver depression were identified and compared when the sample was stratified by ethnicity (WH and WNH) and generation (spouses and children). Patient cognitive impairment was a predictor of caregiver depression only among WH spouses and children, whereas patient psychosis was a predictor only among WNH spouses. Female caregiver gender was the most robust risk factor for caregiver depression, being a predictor in all groups except WH children. Implications of this study include the need for increased clinical sensitivity to depression in ethnic minority caregivers, treatment of psychiatric morbidity in dementia caregivers, and respite care for caregivers with high risk for depression.

Adult↗

How should clinicians discuss hospice for patients with dementia? Anticipating caregivers' preconceptions and meeting their information needs.

This study was designed to determine whether Alzheimer disease (AD) caregivers view the benefits of hospice as more relevant to themselves or to patients, to identify the features of hospice care that are most important to caregivers, and to determine how often these features are described in hospice promotional materials. Telephone interviews were conducted with AD caregivers from a Memory Disorders Clinic of an urban academic medical center (N = 45). A nationwide mail survey of randomly selected hospices was also conducted (N = 66). Caregivers were twice as likely to say that hospice would benefit them than they were to say it would benefit the patient (26 vs. 13; p = 0.002). The features of hospice that were most important to caregivers were continued follow-up evaluation by the patient's primary care provider and hospice's emphasis on helping patients to avoid hospital admission. The least important was the availability of a chaplain. There was moderate agreement between the importance of various hospice features to caregivers, and the representation of that feature in hospice promotional materials. AD caregivers have generally positive opinions about hospice's benefits for themselves. In discussing hospice with AD caregivers, clinicians may want to emphasize selected features of hospice that are particularly important to caregivers.

Adult↗

Combination therapy of donepezil and vitamin E in Alzheimer disease.

A retrospective chart review was performed on 130 patients from the Ohio State University Memory Disorders Clinic to examine the long-term effects of combination therapy with donepezil and vitamin E on patients with Alzheimer disease. Subjects were included if they met National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease, had taken at least 5 mg donepezil and at least 1000 U vitamin E daily, had at least a 1-year follow-up while continuing these medications, and had a Mini-Mental State Examination score of 10-24. The Mini-Mental State Examination was then recorded annually thereafter. These data were compared with the Consortium to Establish a Registry for Alzheimer's Disease database for patients collected prior to the availability of these treatment options. Patients declined at a significantly lower rate as compared with the Consortium to Establish a Registry for Alzheimer's Disease data. The long-term combination therapy of donepezil and vitamin E appears beneficial for patients with Alzheimer disease. Future prospective studies would be needed to compare combination treatment to vitamin E and donepezil alone.

Aged↗

Short-term memory in Parkinson's disease after withdrawal of long-term anticholinergic therapy.

We assessed the short-term memory (STM) using the Visual Paired Associates and the Verbal Paired Associates test, and the motor status at the end of 7.8 +/- 3.7 years of anticholinergic therapy in 22 nondemented patients with Parkinson's disease (PD). Eighteen patients managed to stop anticholinergic therapy. During anticholinergic therapy, STM in PD is significantly worse than in normal controls (CS). Two months after the withdrawal of anticholinergic drugs, the STM retest gain is significantly greater in PD than in CS, and at that time STM in PD did equal CS levels. After withdrawal of anticholinergic therapy, thirteen patients noticed a deterioration of motor function; the dose of levodopa had to be increased in seven patients. We conclude that in nondemented PD patients, long-term anticholinergic therapy probably does not result in irreversible damage to STM, and withdrawal of long-term anticholinergic therapy is feasible in the majority of PD patients.

Aged↗

Brain correlates of memory processes in patients with dementia of Alzheimer's type: a SPECT Activation Study.

Task-induced changes in regional cerebral blood flow (rCBF) during verbal episodic memory activation were compared in 17 right-handed patients with dementia of the Alzheimer's type (DAT) and 20 healthy volunteers. Regional cerebral blood flow was assessed using single photon emission computed tomography (SPECT) and an injection of 133Xe (xenon, isotope of mass 133) in 21 regions of interest (ROI) during rest, passive listening to 36 words, and memorizing of a 12-word list repeated three times. In healthy subjects, memory-listening comparison showed activation of a distributed system involving several left-sided ROI, especially the posterior inferior frontal region. In patients with DAT, the same pattern of activation was found for listening-rest comparison, and no significant changes were found in memory-listening comparison. During listening compared with rest, significant activation was observed in left-sided hypoperfused regions. A significant correlation between memory performance and rCBF recorded in patients with DAT during the memory task was found only in the right lateral frontal region, a region that was not hypoperfused significantly in patients. The involvement of this region might relate to either retrieval effort or actual performance of patients with DAT on the memory task.

Aged↗

The effects of piracetam in children with dyslexia.

Following previous research which suggests that piracetam improves performance on tasks associated with the left hemisphere, a 12-week, double-blind, placebo-controlled study of developmental dyslexics was conducted. Six study sites treated 257 dyslexic boys between the ages of 8 and 13 years who were significantly below their potential in reading performance. Children were of at least normal intelligence, had normal findings on audiologic, ophthalmologic, neurologic, and physical examination, and were neither educationally deprived nor emotionally disturbed. Piracetam was found to be well tolerated in this study population. Children treated with piracetam showed improvements in reading speed. No other effects on reading were observed. In addition, improvement in auditory sequential short-term memory was observed in those piracetam-treated patients who showed relatively poor memory at baseline. It is suggested that longer term treatment with piracetam may result in additional improvements.

Adolescent↗