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Auditory sensory ("echoic") memory dysfunction in schizophrenia.

OBJECTIVE: Studies of working memory dysfunction in schizophrenia have focused largely on prefrontal components. This study investigated the integrity of auditory sensory ("echoic") memory, a component that shows little dependence on prefrontal functioning. METHOD: Echoic memory was investigated in 20 schizophrenic subjects and 20 age- and IQ-matched normal comparison subjects with the use of nondelayed and delayed tone matching. RESULTS: Schizophrenic subjects were markedly impaired in their ability to match two tones after an extremely brief delay between them (300 msec) but were unimpaired when there was no delay between tones. CONCLUSIONS: Working memory dysfunction in schizophrenia affects brain regions outside the prefrontal cortex as well as within.

Acoustic Stimulation↗

Would caregivers of Alzheimer disease patients involve their relative in a decision to use an AD-slowing medication?

OBJECTIVES: The authors examined the factors associated with 1) caregivers' willingness to involve a relative with Alzheimer disease (AD) in a decision to use an AD-slowing treatment; and 2) how caregivers would resolve a disagreement over this decision with the their relative. METHODS: This was a cross-sectional interview study of 102 caregivers of patients with mild-to-severe-stage AD, enrolled in a University Memory Disorders Clinic. RESULTS: Forty-four percent of caregivers (45/102) said that his or her relative would participate in a decision to use an AD-slowing treatment. Logistic regression showed that having less dementia severity, being a female caregiver, and a spousal relationship were all associated with caregivers' involving their relative in this decision. Among the caregivers who said they would involve their relative, the majority said they would resolve disagreements over whether to use the treatment in favor of what the patient wanted, versus what the family wanted for the patient. Male caregivers were less likely to resolve disagreements in favor of the patients' preferences. CONCLUSION: Although most caregivers of patients in mild-to-moderate stages would include these patients in an AD treatment decision, certain caregiver characteristics, such as gender and relationship, are associated with not involving patients in this decision. Physicians working with dementia patients and their family members should take these characteristics into account when discussing treatment options and work with patient-caregiver dyads to improve the communication of preferences.

Adult↗

How do patients with Alzheimer disease rate their overall quality of life?

OBJECTIVE: The authors asked how Alzheimer disease (AD) patients assess their overall quality of life (QOL) and sought to determine the characteristics associated with this assessment. METHODS: The authors performed a cross-sectional survey of 193 persons with mild-to-severe-stage AD in a University Memory Disorders Clinic using a single-item self-assessment of overall QOL. RESULTS: The 181 of 193 patients (94%) able to complete a single-item QOL self-rating had less severe dementia than patients not able to complete, but some had Mini-Mental State Exam scores as low as 0. Most patients rated their QOL as "good" (35%) or "very good" (36%). Latino patients, patients with less education, and depressed patients were more likely to rate their QOL lower. Among patients able to estimate how they thought their family caregiver would rate their QOL (N=173; 90%), there was moderate agreement between this estimate and their self-ratings. CONCLUSION: A single-item global rating of patient QOL could prove useful in assessing QOL of most mild-to-severe-stage AD patients. Affective impairment, more than cognitive or functional impairment, drives this assessment. Screening for and addressing depressive symptoms could improve AD patients' QOL. Despite impairments in insight, patients see a difference in how their caregivers would rate their QOL.

Aged↗

Compromised memory function in schizophrenia and temporal lobe epilepsy.

The purpose of this study was to investigate compromised memory function of schizophrenia patients in comparison with temporal lobe epilepsy patients, whose memory impairments result from a clear lesion. The authors hypothesized that schizophrenia patients would show poorer immediate and delayed recall performances in verbal and visual memory tasks. The study sample consisted of a healthy comparison group of 30 subjects and three patient groups comprising 76 schizophrenia patients, 93 left temporal lobe epilepsy patients, and 72 right temporal lobe epilepsy patients. The authors assessed immediate recall, delayed recall, and delayed retention. Tasks were subdivided into two categories (easy and difficult), and then patient memory dysfunction was compared among the memory tests. The authors observed material-specific memory impairment, where the left temporal lobe epilepsy group showed severe verbal memory impairment and the right temporal lobe epilepsy group showed severe visual memory impairment. A moderate impairment was found in immediate and delayed verbal memory in schizophrenia patients, and the impairment of visual memory was amplified with delayed recall. Such a result can be interpreted not only as a generalized cognitive deficit, but also as an integrative dysfunction involving the mesial temporal and frontal lobes in the left and right hemispheres, whereby the lesion site cannot be determined selectively. Our results show that the selection of a memory task that cannot be influenced by verbal mediation is very important for analyzing memory dysfunction in schizophrenia patients.

Adult↗

Limitation of the Mini-Mental State Examination for the detection of amnesia.

The present study demonstrates the limitation of the Mini-Mental State Examination (MMSE) for detecting the amnestic syndrome. Although neuropsychological testing yielded severe memory deficits in all of the 11 amnesic patients tested, six of the patients obtained total MMSE scores above the standard cutoff score of 24. Further, only six patients completely failed the MMSE recall item, and three patients performed errorlessly on this item. Results from one postencephalitic patient are presented in detail. She performed the serial sevens task very quickly and subsequently recalled all three of the to-be-remembered words. Her performance on other memory tests confirmed that a longer retention interval than that provided by the MMSE is necessary to elicit her memory disorder.

Aged↗

Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats.

Although many studies have examined the acute behavioural effects of cannabinoids in rodents, few have examined the lasting effects of cannabinoids at different developmental ages. This study compared lasting effects of cannabinoid exposure occurring in adolescence to that occurring in early adulthood. Forty, 30-day old (adolescent) and 18, 56-day old (adult) female albino Wistar rats were injected with vehicle or incremental doses of the cannabinoid receptor agonist (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55,940) once per day for 21 consecutive days (150, 200 and 300 microg/kg i.p. for 3, 8 and 10 days, respectively). Following a 21-day drug-free period, working memory was assessed using an object recognition task. Locomotor activity was also measured in the object recognition apparatus via a ceiling-mounted passive infrared sensor. Three days later, anxiety was assessed using a social interaction test. In the object recognition task, significantly poorer working memory was observed in the adolescent but not adult CP 55,940-treated rats. Adolescent, but not adult CP 55,940-treated rats, also exhibited a significant decrease in social interaction with a novel conspecific. These results suggest that chronic exposure to a cannabinoid receptor agonist well after the immediate postnatal period, but before reaching sexual maturity, can lead to increased anxiety and a lasting impairment of working memory.

Aging↗

Symptoms underlying unawareness of memory impairment in patients with mild Alzheimer's disease.

Patients with Alzheimer's disease (AD) are often unaware of their cognitive impairment. This unawareness might have a multifactorial etiology, including impairment of cognitive domains and psychiatric symptoms. We conducted this study to determine the factors underlying unawareness of memory impairment (UMI) in patients with AD. In 103 patients with mild AD, the UMI was quantified as the difference between the patient's self-rating and the rating of the patient's caregiver on a standardized memory questionnaire system, the Everyday Memory Checklist. We then examined the relationships between UMI and memory, attention, language, visuospatial/constructive perception, frontal lobe function, and psychiatric symptoms. UMI was positively associated with memory impairment and delusions when effects of age, sex, and education were partialled out, suggesting that these symptoms are involved in the formation of UMI in the patients. Thus, existing treatments for memory impairment and delusions may be beneficial for increasing the awareness of mild AD patients of their cognitive impairment.

Affective Symptoms↗

Association between premorbid history of depression and current depression in Alzheimer's disease.

The relationship between a premorbid history of depression and the depressive syndrome in Alzheimer's disease (AD) remains equivocal. In the current study, we compared the prevalence of depression among patients with and without a history of mood disturbance prior to the onset of dementia. The sample comprised 243 AD outpatients evaluated consecutively at a university-affiliated memory disorders center. The results indicated that a positive history of depression was more common among patients with current depression compared to those without current depression (23% vs 11%, Fisher's Exact Test, P = .03). This relationship remained significant after controlling for the effects of age, education, gender, ethnicity, and level of cognitive impairment (odds ratio = 2.6, 95% confidence interval = 1.01-6.61, P = .04). Neither gender nor the interaction of gender and history of depression was shown to confer risk for current depressive symptoms. The present investigation suggests that premorbid depression may alter the risk for mood disturbance in AD.

Aged↗

Possible short-term memory loss associated with nafarelin acetate.

OBJECTIVE AND DESIGN: A survey was conducted to determine the occurrence of short-term memory loss in patients using nafarelin acetate nasal spray. SETTING AND PATIENTS: A list of all patients receiving nafarelin acetate from our pharmacy over a four-month period was generated. We contacted and surveyed 16 women. INTERVENTIONS: Each patient was asked to repeat three words at the beginning of the survey and after a series of questions, each patient was asked to recall the three words. Patients were also asked if they believed that their memory was affected by nafarelin acetate nasal spray. RESULTS: Eleven patients (69 percent) recalled three words, 3 (19 percent) recalled two words, and 2 (13 percent) recalled one word at the conclusion of the survey. Nine of 16 patients (56 percent) reported some type of memory difficulty. CONCLUSIONS: Nafarelin acetate nasal spray may adversely affect short-term memory. This effect is not documented in current literature and further investigation is warranted in the possible relationship between gonadotropin releasing hormone agonists, estrogen deficiency, menopause, and short-term memory. Our survey also demonstrates the significance of communication between pharmacists and patients on newly marketed medications.

Administration, Inhalation↗

WAIS digit span-based indicators of malingered neurocognitive dysfunction: classification accuracy in traumatic brain injury.

The present study determined specificity and sensitivity to malingered neurocognitive dysfunction (MND) in traumatic brain injury (TBI) for several Wechsler Adult Intelligence Scale (WAIS) Digit Span scores. TBI patients (n = 344) were categorized into one of five groups: no incentive, incentive only, suspect, probable MND, and definite MND. Performance of 1,063 nonincentive patients (e.g., cerebrovascular accident, memory disorder) was also examined. Digit Span scores included reliable digit span, maximum span forward both trials correct, maximum span forward, combined maximum forward and backward span, Digit Span scaled score, maximum span backward both trials correct, and maximum span backward. In TBI, sensitivity to MND ranged from 15% to greater than 30% at specificities of 92% to 98%. Patient groups with documented brain pathology had higher false-positive error rates. These results replicate previous known-groups malingering studies and provide valuable data supporting the WAIS Digit Span scores in detection and diagnosis of malingering.

Adolescent↗

Extrapyramidal symptoms and signs in Alzheimer's disease: prevalence and correlation with the first symptom.

OBJECTIVES: To determine the prevalence and clinical correlates of extrapyramidal signs (EPS) in outpatients with probable Alzheimer's disease (AD); to examine the appearance of EPS in association with the first symptom that led the patient or family to ask for medical help; to examine the association of the prevalence of EPS with gender, age at onset of the disease, duration of the disease, severity of dementia, functional disability, and potential use of neuroleptics; and to address the issue of the possible role of EPS as a predictive factor for the clinical course of the disease. PATIENTS AND METHODS: We examined 126 patients meeting NINCDS-ADRDA* criteria for probable AD and 29 healthy, nondementia controls of comparable age and gender. Thirteen of the patients taking neuroleptics at the time of the examination were excluded from the main study group and formed a separate subgroup of AD/neuroleptics-positive. Twenty-eight of the AD/neuroleptics-free patients were re-examined during an 18-month period in order to determine the possible role of EPS as a predictive factor of the clinical course of the disease. RESULTS: Only 8 percent of the AD/neuroleptics-free patients were free of EPS, while the corresponding percentage in the control group was 61.5 percent. The most common types of EPS presented in the patient group were hypomimia ([facial mask] 60 percent), difficulty in talking (53.66 percent), bradykinesia (51.4 percent), postural instability (47.33 percent), abnormal gait (34.66), and rigidity (26 percent), respectively. No significant differences were found when examining for the presence of resting tremor, other tremors, dystonias, and dyskinesias. With regard to the presence of EPS and the first symptom, no significant difference was found among patients whose first complaint was memory disorder (probable AD) and patients with other symptoms. When examining the association between the prevalence of EPS and gender or age at onset of the disease, no special correlation was detected. However, such a correlation was found between the prevalence of EPS and duration of the disease, as indicated by the fact that EPS appear in 78.9 percent of the patients with a duration of illness less than two years, but in 97 percent of the patients with a corresponding duration of two years or more. The mean duration of the disease in patients appearing with EPS is found to be 2.68 +/- 1.98 years. The presence of EPS increases proportionally with the progression of the disease and cognitive and functional decline. Patients with poor results in the MMSE (score of less than 11) appear to present EPS at a greater percentage than those with better performance on the examination (MMSE scores greater than 11). With regard to the association between EPS and functional ability in AD, it seems that the presence of EPS imposes difficulties in daily activities, as seen by the fact that patients with EPS have lower FRSSD scores (mean +/- SD: 14.87 +/- 10.53) than patients without EPS (5 +/- 2.58). After controlling for duration of the disease, the use of neuroleptics is found to influence the appearance of EPS in patients with AD. Almost all of the patients AD/neuroleptics-positive patients presented EPS (100 percent), while 92 percent of the AD/neuroleptics-free patients manifested such symptoms. Finally, we re-evaluated 28 patients, who were part of the initial AD/neuroleptics-free group, in order to determine whether the appearance of EPS could have prognostic value for the clinical course of the disease. Patients who presented EPS at initial examination appeared to deteriorate faster, mainly cognitively, but also functionally. The mean decrease in MMSE scores in patients with EPS was found to be 2.65 +/- 3.46; while in patients without EPS at initial visit, MMSE scores were 0.63 +/- 3.88. The functional decline seems to be less influenced by the presence of EPS. The corresponding mean decrease in FRSSD scores of the two groups was 2.1 +/- 5.55 and 1.8 +/- 2.1, respectively.

Aged↗

Challenges in the clinical diagnosis of Alzheimer's disease: influence of "family coaching" on the mini-mental state examination.

The Mini-Mental State Examination (MMSE) is a commonly used clinical tool for evaluating the cognitive aspects of mental function. In this study, 40 consecutive patients presenting to a memory disorder clinic and their caregivers were evaluated for coaching of the patient with respect to MMSE content over the 24 hours prior to clinical evaluation. Caregivers completed a questionnaire concerning MMSE practice sessions with the patient prior to the physician encounter; then, the patients were asked to spell the word "WORM" backwards instead of "WORLD" during the MMSE test. Some or all of the MMSE content was reviewed with the patient prior to the interview by 42.5 percent of the caregivers; 17.5 percent of patients spelled or attempted to spell "WORLD" backwards instead of "WORM". These results demonstrate that coaching of patients prior to administration of the MMSE is not uncommon, and that this needs to be taken into consideration when forming therapeutic decisions based on MMSE results.

Aged↗

Synaptic protein CSF levels relate to memory scores in individuals without dementia.

BACKGROUND: We investigated how cerebrospinal fluid levels of synaptic proteins associate with memory function in normal cognition (CN) and mild cognitive impairment (MCI), and investigated the effect of amyloid positivity on these associations. METHODS: We included 242 CN (105(43%) abnormal amyloid), and 278 MCI individuals (183(66%) abnormal amyloid) from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). For 181 (EMIF-AD MBD) and 36 (ADNI) proteins with a synaptic annotation in SynGO, associations with word learning recall were analysed with linear models. RESULTS: Subsets of synaptic proteins showed lower levels with worse recall in preclinical AD (EMIF-AD MBD: 7, ADNI: 5 proteins, none overlapping), prodromal AD (EMIF-AD MBD only, 27 proteins) and non-AD MCI (EMIF-AD MBD: 1, ADNI: 7 proteins). The majority of these associations were specific to these clinical groups. CONCLUSIONS: Synaptic disturbance-related memory impairment occurred very early in AD, indicating it may be relevant to develop therapies targeting the synapse early in the disease.

Humans↗

The role of electroconvulsive therapy in the treatment of depressive illness in old age.

Electroconvulsive therapy is an important treatment in the depressive states of late life, and there is general agreement about the indications for its use in old age psychiatry. Indeed, old age may be associated with a better response to ECT than that in younger age groups. The additional risk involved through physical problems in the elderly is not great when compared with that of continuing depression and of the side-effects of alternative treatments. Temporary memory disorders and confusion may occur, but are minimised if unilateral electrode placement is used. Some patients treated with unilateral ECT do not respond, but will respond to bilateral treatment. Anxiety over unwanted treatment effects, which can lead to ineffective treatment of depressive illness, must be outweighed by knowledge of the dangers of leaving depression untreated in old age.

Aged↗

Neuropsychology.

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Brain↗

Evaluation of a neural network model of amnesia in diffuse cerebral atrophy.

A digital computer program generating a simulated neural network was used to construct a model which can show behaviour resembling human associative memory. The experimental network uses distributed storage, and, in this respect, its functional organisation resembles that suggested by reported observations of neuronal activity in the human temporal lobe during memory storage and recall. Inactivation of increasing numbers of randomly distributed network units simulated advancing cerebral atrophy. This caused progressive impairment of performance, resembling the gradual deterioration of memory function observed in chronic diffuse cerebral degeneration. Unit inactivation had similar effects on recall whether the same units were inactivated before or after learning. This differs from most relevant observations of amnesia resulting from diffuse cerebral disease. While the model may functionally resemble long-term information storage sites in the brain, other cerebral mechanisms participating in learning and remembering are also damaged by diffuse cerebral atrophy.

Amnesia↗