Absence Of Cognitive Impairment Research Articles

Progress in clinical neurosciences: the evidence for ALS as a multisystems disorder of limited phenotypic expression.

Traditionally, amyotrophic lateral sclerosis (ALS) is considered to be a unique neurodegeneration disorder in which motor neurons are selectively vulnerable to a single disease process. Our current understanding of ALS, however, suggests that this is far too limited an approach. While motor neuron degeneration remains the central component to this process, there is considerable phenotypic variability including broad ranges in survivorship and the presence or absence of cognitive impairment. The number of familial variants of ALS for which unique genetic linkage has been identified is increasing, attesting further to the biological heterogeneity of the disorder. At the cellular level, derangements in cytoskeletal protein and glutamate metabolism, mitochondrial function, and in glial interactions are clearly evident. When considered in this fashion, ALS can be justifiably considered a disorder of multiple biological processes sharing in common the degeneration of motor neurons.

Further experience of nonagenarians with hip fractures

Our purpose was to investigate the factors after predictive outcome 3 months after the injury in terms of mortality and effective independent walking of nonagenarians with hip fracture. A prospective study was carried out for 2 yr in the orthopaedic wards on patients referred to geriatricians. The data were subjected to logistic regression forward stepwise analysis. Eighty-nine patients were included in the study; 55 (61.8%) had a trochanteric fracture and 86 required a surgical procedure. Before the fracture, 83 patients (93.3%) were able to walk by themselves or with minimal supervision. Forty-three patients (48.3%) had an American Society of Anaesthesiologists’ of III–IV score. The mean number of postoperative complications was four. Mean hospital stay was 18.2 days. Within 3 months, 19 patients (21.3%) had died and 58 (69%) were living in their previous residence. Thirty-three (50% of living patients) were able to walk by themselves or with minimal help within 3 months of the fracture. Predictive variables for 3-month mortality were pre-fracture dependence on others for personal toilet and the presence of cognitive impairment. Predictive variables for independent efficient walking were bowel control and absence of cognitive impairment before the fracture, as well as no development of bed sores during hospitalization. These nonagenarian patients with hip fractures show low perioperative mortality, frequently return to their previous accommodation and present a limited recovery of walking ability.

Absence of cognitive impairment or decline in preclinical Alzheimer's disease.

To determine whether clinically nondemented elderly individuals with pathologically confirmed preclinical AD are characterized by cognitive decline as measured by psychometric tests before death. Psychometric performance was examined retrospectively in 14 individuals who were nondemented at time of death and grouped in accordance with their neuropathologic findings: 1) Healthy brain (n = 9) was characterized by the absence of senile plaques or by only patchy neocortical deposits of plaques; 2) preclinical AD (n = 5) was characterized by neuritic and diffuse plaques distributed throughout the neocortex. All individuals showed neurofibrillary pathologic change in medial temporal lobe structures. For comparison, we also evaluated 10 individuals who died in the earliest symptomatic stage of dementia of the Alzheimer type (DAT). All individuals had been assessed by clinical and psychometric measures during life. The psychometric measures yielded a standardized factor score that represented global cognitive performance. At the last assessment before death, individuals with very mild DAT were impaired on the factor score and on individual psychometric measures with respect to the nondemented individuals. Those nondemented individuals with preclinical AD did not differ in performance from those with healthy brains. For individuals with at least three psychometric assessments during life, there was no decline in performance for either those with healthy brains (n = 5) or preclinical AD (n = 3), although decline was evident for very mild DAT individuals (n = 5). Pathologically confirmed preclinical AD is not associated with cognitive impairment or decline, even on measures shown to be sensitive to very mild DAT.

Predictive validity of the Neurobehavioural Cognitive Status Examination (NCSE) in a post-acute rehabilitation setting

Within the context of a post-acute rehabilitation setting, association and agreement between results from the Neurobehavioural Cognitive Status Examination (NCSE) and from the neuropsychological (NP) evaluation are examined. All participants (n = 48) had sustained a severe traumatic brain injury and NCSE testing preceded NP testing by an average of 1 month. A significant relationship and fair classification agreement (i.e. presence or absence of cognitive impairment) was found between the overall results from NCSE and NP evaluation. Significant relationships were also observed between most NCSE subtests and paired NP tests thought to be assessing the same cognitive domains. However, the classification agreement (i.e. the presence or absence of deficient performance) between most NCSE subtests and paired NP tests was poor. The findings are discussed from the standpoint of individual treatment planning.

Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV+ patients.

To determine whether the concentrations of the neuronal marker N-acetylaspartate (NAA) and the choline-containing metabolites (Cho) are altered in the subcortical brain of HIV+ patients who are cognitively normal and clinically asymptomatic, and to determine whether these alterations are greater in the presence of cognitive impairments and clinical symptoms. Pathologic studies suggest that subcortical gray matter carries a heavy HIV load, and neuropsychological test results are consistent with involvement of subcortical and frontostriatal brain systems in HIV disease. Noninvasive proton magnetic resonance spectroscopy (1H MRS) suggests neuronal preservation and macrophage infiltration in the subcortical brain of clinically symptomatic and cognitively impaired HIV+ individuals. Improved 1H MRS methods may allow the early detection of metabolite alterations in the subcortical brain of asymptomatic HIV+ individuals. Two-dimensional 1H MRS imaging was performed on 30 HIV- control subjects and 70 HIV+ patients with varying severities of systemic disease and neuropsychological impairments, but without cerebral opportunistic infections. Subcortical Cho was elevated in HIV+ patients compared with control subjects regardless of the presence or absence of cognitive impairment or clinical symptoms. Subcortical NAA was lower than control NAA only in severely cognitively impaired HIV+ subjects. Subcortical NAA correlated with performance on a variety of neuropsychological tests but not with Centers for Disease Control clinical stage, whereas high-thalamic Cho was associated with low CD4 lymphocyte counts. 1H MRS imaging detects higher Cho in subcortical brain early in HIV disease, when individuals are clinically and neuropsychologically asymptomatic, whereas lower NAA is only found in subcortical brain in individuals with severe neuropsychological impairments. Quantitative 1H MRS imaging may play a role in the objective assessment of the presence, magnitude, and progression of brain involvement in HIV infection.

Cognitive and physical measures in rehabilitation of patients with lupus.

During the past 2 years, four papers describing new research studies and three papers reviewing the literature were published. These seven papers address longstanding issues, including 1) the presence or absence of cognitive impairment in systemic lupus erythematosus (SLE), 2) the prevalence of such impairment within SLE and related conditions (eg, antiphospholipid antibody syndrome, active vs inactive SLE), 3) the specific pattern of cognitive functions impaired and the possibility of a "lupus-specific" pattern, 4) the etiopathogenesis of cognitive impairments and the potential role of confounding factors such as corticosteroid use or depression, and 5) longitudinal studies examining the course of SLE-related cognitive impairment. The review period also includes two studies using both static and functional neuroimaging to identify the potential relation between neuroanatomic or neurophysiologic abnormalities and cognitive impairment in patients with SLE. No papers specific to Sjögren's syndrome were identified.

What is the accuracy of the clinical diagnosis of multiple system atrophy? A clinicopathologic study.

The presentation of symptoms for multiple system atrophy (MSA) varies. Because there are no specific markers for its clinical diagnosis, the diagnosis rests on the results of the neuropathologic examination. Despite several clinicopathologic studies, the diagnostic accuracy for MSA is unknown. To determine the accuracy for the clinical diagnosis of MSA and to identify, as early as possible, those features that would best predict MSA. One hundred five autopsy-confirmed cases of MSA and related disorders (MSA [n=16], non-MSA [n=89]) were presented as clinical vignettes to 6 neurologists (raters) who were unaware of the study design. Raters identified the main clinical features and provided a diagnosis based on descriptions of the patients' first and last clinic visits. Interrater reliability was evaluated with the use of kappa statistics. Raters' diagnoses and those of the primary neurologists (who followed up the patients) were compared with the autopsy-confirmed diagnoses to estimate the sensitivity and positive predictive values at the patients' first and last visits. Logistic regression analysis was used to determine the best predictors to diagnose MSA. For the first visit (median, 42 months after the onset of symptoms), the raters' sensitivity (median, 56%; range, 50%-69%) and positive predictive values (median, 76%; range, 61%-91%) for the clinical diagnosis of MSA were not optimal. For the last visit (74 months after the onset of symptoms), the raters' sensitivity (median, 69%; range, 56%-94%) and positive predictive values (median, 80%; range, 77%-92%) improved. Primary neurologists correctly identified 25% and 50% of the patients with MSA at the first and last visits, respectively. False-negative and -positive misdiagnoses frequently occurred in patients with Parkinson disease and progressive supranuclear palsy. Early severe autonomic failure, absence of cognitive impairment, early cerebellar symptoms, and early gait disturbances were identified as the best predictive features to diagnose MSA. The low sensitivity for the clinical diagnosis of MSA, particularly among neurologists who followed up these patients in the tertiary centers, suggests that this disorder is underdiagnosed. The misdiagnosis of MSA is usually due to its confusion with Parkinson disease or progressive supranuclear palsy, thus compromising the research on all 3 disorders.

Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study.

PET measurements of regional cerebral blood flow (rCBF) were used to explore frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS). An activation paradigm of executive frontal lobe function (verbal fluency), which contrasted rCBF during word generation and word repetition, was used. Two groups of ALS patients, defined by the presence or absence of cognitive impairment (ALSi) (impaired, n = 6: ALSu unimpaired, n = 6) were compared with healthy age-matched controls (n = 6). Patient selection was based on prior performance on a written test of verbal fluency. Additional neuropsychological assessment of the patients revealed evidence of executive and memory dysfunction in the ALSi group only, with marked deficits in tests of intrinsic generation. The ALSi patients displayed significantly (P < 0.001) impaired activation in cortical and subcortical regions including the dorsolateral prefrontal cortex (DLPFC; areas 46 and 9), lateral premotor cortex (areas 8 and 6), medial prefrontal and premotor cortices (areas 8 and 9), insular cortex bilaterally and the anterior thalamic nuclear complex. Although the three groups showed matched word generation performance on the scanning paradigm, the ALSu group displayed a relatively unimpaired pattern of activation. These results support the presence of extra-motor neuronal involvement, particularly along a thalamo-frontal association pathway, in some non-demented ALS patients. In addition, this study suggests dysfunction of DLPFC in some ALS patients with associated cognitive impairments.

A positron emission tomography study of frontal lobe function (verbal fluency) in amyotrophic lateral sclerosis

Positron emission tomography (PET) was used to investigate the location of cerebral cortical and subcortical abnormalities in non-demented patients with amyotrophic lateral sclerosis (ALS). Involvement of the frontal lobes was investigated with a task of executive frontal lobe function (verbal fluency/word generation), using a PET activation paradigm. Two groups of ALS patients defined by the presence or absence of cognitive impairment were tested. ALS patients who had cognitive impairments showed a region of cortical and subcortical dysfunction which extended across a wide area of the frontal lobes, and included the insular cortex and thalamic nuclear complex. These findings support the notion that extra-motor involvement is relatively common in ALS and broadens concepts of selective vulnerability in ALS.

Subtle extrapyramidal signs can predict the development of dementia in elderly individuals.

To assess the significance of mild extrapyramidal signs (EPSs) in aging, we prospectively followed 228 elderly individuals without dementia or major neurologic disease at baseline. Seventy-three (32%) showed mild idiopathic EPSs at baseline assessment and 32 (14%) of these 228 individuals met NINCDS-ADRDA criteria for probable or possible Alzheimer's disease on follow-up. While none of these individuals developed Parkinson's disease, those with more than one EPS at baseline were significantly more likely to become demented during follow-up than were those with one or no EPS, an association not confounded by age, education, or gender. Individuals with more than one EPS and with cognitive impairment (CI) at baseline were at highest risk for dementia. EPSs were also independently associated with incident dementia in the absence of CI at baseline. We conclude that mild EPSs are a significant predictor of dementia in elderly individuals.

Cognitive impairment in the elderly medically ill: How often is it missed?

AbstractOne hundred and sixty‐three patients over 65 years of age admitted to the acute medical wards of a district teaching hospital were studied for prevalence and type of cognitive impairment. Findings from research assessments, where possible using a cognitive rating scale, were compared with detection of impairment by medical and nursing staff involved in patients' clinical management. 30.7% of patients were judged by us to show definite or probable cognitive impairment, a figure substantially higher than that detected by hospital staff. Outcomes in terms of death, duration of admission and discharge location were related to the presence or absence of cognitive impairment and whether impairment was due to delirium, dementia or a mixed syndrome. The low rate of detection of cognitive impairment is discussed, and suggestions made to improve detection in acute elderly medical inpatients.

Late paraphrenia, advanced schizophrenic deterioration and dementia

AbstractThis is a report of a clinical case presentation from the Neuropsychiatry Conference held at Fulbourn Hospital, Cambridge on March 13, 1992. The conference, chaired by Dr Nigel Hymas, was asked to comment on the diagnosis of a case first referred during September 1990. A 60‐year‐old man with no previous history of psychiatric illness presented with persecutory ideation, delusions and hallucinations in the absence of cognitive impairment. At the time, the initial tentative psychiatric diagnosis was one of late paraphrenia, but it later became clear that the patient was dementing. Were the paraphrenia and dementia related? If so, how? What was the nature of the dementing illness? Could life‐long personality abnormalities have been the earliest expression of cerebral abnormalities predisposing him to his current illness? Incompatible evidence from clinical features, functional brain scanning and comprehensive neuropsychological testing demonstrates the inadequacy of current diagnostic criteria.

Absence of cognitive impairment after more than 100 lifetime ECT treatments

The cognitive function scores and subjective memory complaints of eight patients who had each received more than 100 treatments with bilateral modified since wave ECT were equivalent to those of matched patients who had never received ECT. The results suggest that patients given many ECT treatments over several courses do not manifest measurable cognitive impairment at long-term follow-up.