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White matter lesions impair initiation of FAS flow.

Word fluency performance is known to rely on left frontal cortical regions and has also been shown to be affected by lesions in the white matter, which may be seen as white matter hyperintensities (WMH) on magnetic resonance imaging. However, word fluency may be divided into two independent components, initial and late performance, separated in time [J Clin Exp Neuropsychol 1998;20:137-143]. The purpose of the current study was to investigate the relationship between the two components of FAS fluency performance and WMH. Patients varying in degree of memory impairment participated: Alzheimer's disease, mild cognitive impairment and subjective memory disorder. WMH were rated with the Scheltens scale in the periventricular and deep subcortical areas. Results demonstrated that WMH in this sample of patients may be summarized in two indices according to a principal factor analysis, one anterior factor mainly related to WMH in the frontal lobes and adjacent to ventricles, and a second posterior factor related to parietal and occipital WMH. The initial FAS performance was related to anterior WMH, in particular left frontal or lateral periventricular hyperintensities, whereas the late FAS performance was not related to any index of WMH.

Aged↗

[New protocol for memory-related potential].

A new P300 testing protocol for evaluating memory function is proposed. Four stimuli (S1, S2, S3 and S4) are presented to the subject at 1.5 sec intervals and the subject is instructed to judge whether S4 was the same (80%) or not (20%) as S1, as well as whether S3 was the same (80%) or not (20%) as S2. The S2-S3 comparison acts as an attention shifting mechanism, and by inserting this comparison between S1 and S4, the subject must memorized S1 at the memory site in the brain until S4 is presented. This protocol was performed using both auditory and visual stimulations with 24 college students (age range: 19-28 years old) and a patient (23 years old) with bilateral medial temporal lobe lesions caused by limbic encephalitis. The P300 brain potentials after S3 and S4 were compared. The Wechsler memory scale-revised (WMS-R) test was also assessed in all subjects. The latency of P300 after S4 had a significantly (p < 0.01) longer than that after S3. The latency of P300 after S4 in the patient, who showed the severe auditory as well as the mild visual memory impairment, was longer than the mean + 2 SD in the normal subjects for auditory stimuli, but not for visual stimuli, whereas the latency of P300 after S3 in the patient was longer than the mean + 2 SD in the normal subjects only for visual stimuli. The brain potential after S4 might be more reflective of a degree of memory disorder as compared with that after S3. Furthermore, the latency of P300 after S4 showed a more significant correlation with some WMS-R scores (verbal memory, general memory and verbal delay) than the latency of P300 after S3. These results suggest that measuring the P300 latency after attention shifting in the new protocol is useful for the evaluation of memory functions.

Acoustic Stimulation↗

Diagnosis-seeking at subspecialty memory clinics: trigger events.

BACKGROUND: Research has shown that dementia often goes unrecognized, and diagnostic assessment is often further delayed. Understanding families' decision to seek care at memory clinics is relevant to efforts to facilitate early diagnosis. OBJECTIVE: To examine the population seeking care at two memory clinics and the triggers causing caregivers to seek diagnostic assessment for a family member. METHOD: We surveyed a consecutive sample of caregivers who accompanied a patient to an assessment at two university memory disorders clinics. Caregivers (n=416) described events that led them to seek a memory assessment for the patient, as well as who first suggested an assessment and diagnosis received. RESULTS: Changes in the patient (cognitive, personality/behavioral, physical, or unspecified) accounted for 81% of 903 trigger events reported. Nearly half of the caregivers noting specific patient changes recorded some combination, rather than cognitive changes alone. Of the 338 respondents who noted a change in the patient as a trigger, 85% specified at least one cognitive change, while 40% specified at least one personality/behavioral change. Memory loss was most frequent trigger reported, followed by disorientation and recommendations (lay or professional). Caregivers themselves and non-specialist physicians were the most frequent sources of recommendations noted by all respondents. CONCLUSION: A broad range of trigger events, beyond cognitive or symptomatic changes, caused caregivers to seek diagnosis at a memory clinic. Awareness of triggers significant to families may help physicians reduce the number and severity of events needed to convince caregivers a memory assessment is indicated.

Aged↗

Misidentification syndromes related to face specific area in the fusiform gyrus.

The "delusional misidentification syndromes" are a group of uncommon and varied disorders in which, in typical form, the patient thinks that a particular familiar person is someone else or a certain familiar place is a duplicate. Although first identified and considered a memory disorder by Pick, evidence in support of this has been difficult to identify. They have been most often seen in various psychotic and organic brain diseases but lesions have been generally diffuse although the right temporal lobe has been implicated. A patient was investigated who abruptly developed a disorder wherein she misidentified her husband as her deceased sister and claimed that her home was a duplicate of her real home that were typical of Frégoli syndrome and Pick's reduplicative paramnesia, respectively. A discrete area of brain damage, probably ischaemic, in this patient was seen on MRI in the anterior part of the right fusiform gyrus and a smaller area in the nearby anterior middle and inferior temporal gyri with associated parahippocampal and hippocampal atrophy. A high order nervous system function that is devoted to the identification of faces is located in the adjacent midportion of the fusiform gyrus and a similar locus for environmental scenes, termed the parahippocampal place area, is present in the bordering parahippocampal gyrus. The misidentification phenomena in this case can be explained by disruption of the connections of these highly specialised areas with the most anterior inferior and medial part of the right temporal lobe where long term memory and mechanisms for the retrieval of information that are required for the visual recognition of faces and scenes are stored.

Aged↗

[Memory clinic in the day hospital].

Our Memory Clinic at the Day Hospital has developed from years of existing services offered for the outpatient diagnosis of memory disorders. This article presents how such two- to three-day outpatient diagnostic programs are held. After an initial consultation, the patient is admitted to the day clinic. Then a survey of the patient's daily activities is taken, a semi-standardized interview is conducted with patients and the caregivers; neuropsychological tests and a somatic examination including a functional assessment are carried out. In the following, we will discuss how the diagnosis is subsequently rendered on the basis of these findings. Frequently asked questions, common problems and diagnostic difficulties will be elucidated, while focusing on diagnostic and therapeutic discussions and the contents of the consultations.

Activities of Daily Living↗

Behavioral characteristics in mice with brain lesions induced by hypertonic saline.

Behavioral and histopathological characteristics were studied in mice treated repeatedly with hypertonic saline. In passive avoidance response using a step-through-type shuttle box, the mice treated with hypertonic saline showed shorter latency than control mice. No changes were observed in active avoidance response using a two-way-type shuttle box, spontaneous motor activity or motor function. Histopathological examination revealed marked and frequent degeneration and loss of neurons in the hippocampus as compared with animals after single treatment. The animals with severe hippocampal lesions showed impairment of passive avoidance response. The present brain lesions resulting from repeated treatment with hypertonic saline in mice are considered to be a possible model for memory disorders caused by hippocampal lesions in humans.

Animals↗

Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia.

The specific neural substrate underlying the amnesia in alcoholic Korsakoff's psychosis is poorly defined because of the considerable brain damage found in many non-amnesic alcoholics, particularly those with Wernicke's encephalopathy. Using operational criteria to identify alcoholics with and without Korsakoff's psychosis, we have shown that many of the cortical and subcortical regions involved in the encoding and retrieval of episodic memory are either unaffected (hippocampus) or damaged to the same extent (prefrontal cortex and the cholinergic basal forebrain) in both amnesic and non-amnesic alcoholics. In the present study we analysed the diencephalic regions involved in episodic memory to determine the neural substrate for the amnesia observed in alcoholic Korsakoff's psychosis. The number of neurons in spaced serial sections containing the hypothalamic mamillary nuclei and the anterior and mediodorsal thalamic nuclei was estimated using unbiased stereological techniques. Neurodegeneration of the hypothalamic mamillary nuclei and the mediodorsal thalamic nuclei was substantial in both non-amnesic and amnesic alcoholics with Wernicke's encephalopathy. However, neuronal loss in the anterior thalamic nuclei was found consistently only in alcoholic Korsakoff's psychosis. This is the first demonstration of a differentiating lesion in alcoholic Korsakoff's psychosis and supports previous evidence that degeneration of thalamic relays are important in this memory disorder.

Aged↗

Experimental dissociation of memory systems in mice: behavioral and neurochemical aspects.

Evidence for different types of memory in mice may lead to development of animal models for human memory disorders and provides informations on neurobiological systems underlying these processes. Series of experiments in mice, using a 8-arm radial maze with or without cholinergic drugs or chronic alcohol consumption supply arguments for multiple memory stores and for cholinergic influence greatest for short-term system. Studies of differential cholinergic activation following training militate for dissociation in time of hippocampal and cortical cholinergic pathways. Age-related memory involvement seems to be associated with an attenuation of central cholinergic activation. Several problems inherent to sensitivity and selectivity of the tasks remain in discussion.

Animals↗

[Mnemonic performance in patients following surgery to treat an aneurysm affecting the anterior circulation of the brain].

INTRODUCTION: Patients submitted to surgery to treat a brain aneurysm, who have suffered a subarachnoid haemorrhage, sometimes present cognitive disorders that can affect their social, familial, academic or occupational relationships. Memory disorders are frequent, although other cognitive functions may also be affected. AIMS: The purpose of this research work was to study performance in logical verbal memory and visual-constructional memory in subjects following a surgical intervention (at least a year ago) to treat an aneurysm in the territory of the anterior circulation of the brain. We also wanted to analyse whether the location of the aneurysm in the brain had any effect on memory performance. PATIENTS AND METHODS: We examined a sample of 24 adult subjects of both sexes, with no previous history of cognitive or psychiatric disorders, who had undergone surgical treatment of brain aneurysms in the middle cerebral, anterior communicating and posterior communicating arteries. Neuropsychological tests were performed to assess the general cognitive status, as well as logical verbal and visual-constructional memory. RESULTS: 79% of the patients present a general cognitive status within the range of what could be considered to be normal. In logical verbal memory, 92% present performances within the limits of the expected range of values and 83% did the same in visual-constructional memory. Depending on the location of the aneurysm, significant differences were only found in the delayed evocation of logical verbal material. CONCLUSIONS: A year after the intervention, most of the patients present a pattern of normality in the general cognitive status, and in logical verbal and visual-constructional memory. Yet, in spite of the good neurological resolution, alterations to memory are still to be found, although less frequently. The anatomical location of the aneurysm in the brain affects performance in tasks involving delayed logical verbal memory.

Adult↗

Effects of AF102B and tacrine on delayed match-to-sample in monkeys.

1. Object working memory, a function which declines in aging and dementia, was tested in young and aged pretrained monkeys using a delayed match-to-sample task. 2. During drug treatment, monkeys were given the m 1 muscarinic agonist AF102B (0.1-2.1 mg/kg i.m.), the cholinesterase inhibitor tacrine (0.5-2.0 mg/kg p.o.), or vehicle controls in a repeated measures design to assess putative cognitive enhancement. 3. Both agents improved task performance in both young and aged monkeys, AF102B yielding equivalent or greater, and less variable, improvement than tacrine. 4. AF102B may represent a low-toxicity alternative to tacrine for the treatment of age-related memory disorders.

Age Factors↗

No association between subjective memory complaints and apolipoprotein E genotype in cognitively intact elderly.

OBJECTIVE: This cross-sectional study examined the relationship between subjective memory complaints and the apolipoprotein epsilon 4 allele (epsilon4), a genetic risk factor for Alzheimer's disease (AD), among cognitively normal subjects identified from a community memory screening. DESIGN: The sample comprised 232 consecutive white non-Hispanic older adults who presented to a free community-based memory-screening program at a University affiliated memory disorders center. Participants were classified as cognitively normal based on scores on the age and educated adjusted Folstein Mini-Mental Status Exam (MMSAdj) and a brief Delayed Verbal Recall Test (DRT). Subjects were assessed for APOE genotype, subjective memory complaints (Memory Questionnaire, MQ), depressive symptoms (Hamilton Depression Rating Scale, HDRS), and history of four major medical conditions that have been associated with memory loss (stroke/transient ischemic attack [TIA], atherosclerotic heart disease, hypertension, and diabetes). A hierarchical regression analysis was performed to examine the association between APOE genotype and memory complaints after controlling for a host of potential confounding factors. RESULTS: The APOE epsilon4 allele frequency for cognitively normal subjects was 0.13. Subjective memory complaints were predicted by depressive symptoms and a history of stroke/TIA. They were not associated with APOE genotype, MMSAdj score, DRT score, age, education, gender, and reported history of atherosclerotic heart disease, hypertension, or diabetes. CONCLUSION: The results did not suggest an association between subjective memory complaints and the APOE epsilon4 allele in this sample of cognitively intact subjects. This indicates that memory complaints may confer risk for future dementia through pathways independent of APOE genotype. The results also show that older adults with memory complaints are at increased risk for underlying depression.

Aged↗

BIMU 1 and RS 67333, two 5-HT4 receptor agonists, modulate spontaneous alternation deficits induced by scopolamine in the mouse.

The present study was conducted to determine the effects of two potent 5-HT4 receptor agonists, BIMU 1 (1 (3-ethyl-2,3-dihydro-N-[endo-8-methyl-8-azabicyclo (3.2.1)-oct-3-yl]-2-oxo-1H) benzimidazole-1-carboxamide hydrochloride; 1, 3, 10 mg/kg, i.p.) and RS 67333 (1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-butyl-4-piperidinyl)-1-propanone; 0.25, 0.5, 1 mg/kg, i.p.) on the learning impairment induced by the muscarinic acetylcholine receptor antagonist, scopolamine (1 mg/kg) in mice. Working memory was examined by observing spontaneous alternation behavior in the Y-maze test. Both BIMU 1 (10 mg/kg) and RS 67333 (1 mg/kg) prevented the scopolamine-induced alternation deficits, whereas no effect could be evidenced on locomotor or emotional indices. The reversal actions of BIMU 1 and RS 67333 on this cognitive dysfunction were abolished by the selective 5-HT4 receptor antagonist GR 125487 (1-[2-[(methyl sulfonyl)-amino]-ethyl]-4-piperidinyl-methyl-5-fluoro-2-methoxy-1H-indole-3-carboxylate; 10 mg/kg, i.p.). When given alone at the same doses, none of the three serotonergic agents had any measurable effect. These results demonstrate the ability of 5-HT4 receptor agonists to reverse spontaneous working memory deficits and further confirm the therapeutic potential of such ligands in the treatment of cognitive alterations that associate short-term working memory disorders and cholinergic hypofunction.

Aniline Compounds↗

Evaluation of the errorless learning technique in children with traumatic brain injury.

OBJECTIVE: To compare errorless learning with trial-and-error (T&E) learning of declarative facts in children with memory disorders secondary to traumatic brain injury (TBI). DESIGN: Retrospective within-subjects concurrent treatment design. SETTING: Participants' school or home. PARTICIPANTS: Thirty-four children, ages 6 to 18 years, with mild, moderate, or severe postacute TBI who met criteria for memory impairment. INTERVENTION: Conditions consisted of an errorless learning method and a T&E method. Within a session, half the items were taught with the errorless learning method and half with the T&E method. Each child received two 1-hour sessions a week for 7 weeks. MAIN OUTCOME MEASURES: Relative effectiveness of errorless learning and T&E methods for (1) initial learning and (2) retention over time for learned items. RESULTS: There was an advantage for T&E on initial learning. In children with mild, but not moderate or severe TBI, 2-day retention was better with the errorless learning technique; 7-day retention was better with errorless learning in young children with mild TBI. Seventy-seven-day retention revealed an advantage for errorless learning in younger children with severe TBI. CONCLUSIONS: Findings did not support errorless learning as a generalized intervention for learning difficulties after TBI or identify specific age- or injury-severity groups that benefited from this technique.

Adolescent↗

Frontal-type memory impairment associated with thalamic damage.

The present case report adds further evidence to the hypothesis that material-specific memory problems arise from unilateral thalamic damage and that frontal cortical dysfunction may affect the nature of the memory disorder. A 64-year old patient who had suffered an ischemic lesion limited to the right anterior thalamus showed marked deficits in immediate and delayed recall of visuospatial material and face recognition. In addition, there was evidence of frontal-type memory problems including impaired spatial working memory, increased forgetting rates, poor prospective memory and inadequate elaborative encoding. Concomitant behavioral changes characterized by increased irritability and disinhibition also supported the hypothesis of frontal lobe dysfunction after thalamic damage.

Brain Diseases↗

The effect of a memory screening program on the early diagnosis of Alzheimer disease.

CONTEXT: Alzheimer Disease (AD) is often diagnosed at a moderately advanced stage, even though its early detection has become increasingly important, because of the continuing development of treatments that may improve its outcome. OBJECTIVE: To determine if a free memory screening program is associated with an earlier diagnosis of AD, compared with traditional referral methods, such as by physicians and family members. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of 1489 consecutive patients with AD who presented to an outpatient memory disorders clinic between 1993 and 2002. Subjects were classified according to referral source (memory screening, physician, family/friend, other), and self-reported ethnicity (white non-Hispanic, white Hispanic). The associations between referral source and the presenting cognitive and behavioral status of subjects were evaluated using analysis of variance and logistic regression analyses, after controlling for potentially confounding factors. MAIN OUTCOME MEASURES: Score on the Folstein Mini-Mental State Examination (MMSE), duration of cognitive symptoms, and presence of psychosis, defined as delusions and/or hallucinations. RESULTS: After controlling for ethnicity, gender, and the year of diagnosis, subjects with AD, who were referred by the memory screening program, scored significantly higher at presentation on the MMSE (20.8 +/- 5.7), than those referred by physicians (18.8 +/- 6.6), family/friends (16.8 +/- 6.6), or other referral sources (15.3 +/- 7.1). Subjects with AD, referred by the memory screening program, also had a lower reported duration of illness at presentation, and a decreased frequency of psychosis compared with those referred by family/friend and other methods. Other factors related to a diagnosis of AD at a later stage included female gender, Hispanic ethnicity, and a diagnosis early in the 1993 to 2002 time period. CONCLUSIONS: The memory screening program referred patients with AD to a memory clinic at an earlier phase of illness compared with traditional methods such as physician referral.

Aged↗

[Severe mental disorders after prolonged post-traumatic coma].

Using observation in a number of patients with severe closed head injuries followed by prolonged coma and of which three are reported in detail, the authors present an analysis of the resulting psychiatric problems. After a brief review of the literature they suggest a central psychopathological "core" common to such head injuries beneath their seemingly diverse symptomatology. This "core" seems to be built up around the following disturbances: 1) Memory disorders; 2) Perceptual problems and difficulties with the association of ideas; 3) Excessive tiredness and concomitant reduction in the powers of concentration.

Adult↗

Selective dorsolateral frontal lobe dysfunction associated with diencephalic amnesia.

We report three cases with unilateral thalamic ischemic lesions that resulted in lasting material-specific memory impairments and concomitant selective frontal lobe-related cognitive deficits. In two cases the lesions were limited to the left thalamus, and in the third the right thalamus was involved. These deficits were associated with ipsilateral diencephalic, striatal, and dorsolateral prefrontal hypoperfusion. The damage implicated the ventral anterior nucleus, the mamillothalamic tract, and the rostroventral internal medullary lamina. These findings suggest that medial thalamic damage involving the ventral and rostral sector of the dorsal thalamus will concurrently affect functionally and neurally distinct limbodiencephalic pathways and diencephalic connections with the frontal cortex. A review of the neuropsychological and neuroimaging findings from previously reported cases with vascular lesions of the thalamus further supports this contention. The presence of frontal lobe-related cognitive deficits, though not obligatorily related to the memory problems, may contribute to some aspects of the memory deficits and affect the nature of the memory disorder observed in some cases with diencephalic amnesia.

Aged↗