A multidisciplinary memory clinic in a neurological setting: diagnostic evaluation of 400 consecutive patients

This report describes the operation of a multidisciplinary university hospital memory clinic in a neurological setting, and the diagnostic evaluations in 400 consecutive patients referred for cognitive symptoms and possible dementia during a period of 27 months (1 September 1995-31 December 1997). The mean age of the patients was 63.6 years (range 19-97). On clinical and neuropsychological examination, 46% of the patients fulfilled DSM IV criteria for dementia, 5% had selective amnesia, and 14% had other selective cognitive deficits. The remaining patients had either no significant cognitive deficits (31%) or were not evaluable (4%). A wide range of disorders from the fields of neurology, psychiatry, neurosurgery and internal medicine were identified as the underlying etiologies for the cognitive symptoms. Potentially reversible conditions were observed in 26% of the patients, not including the 11% in whom no specific underlying disease was identified. Concomitant conditions or risk factors with a potential influence on cognitive functions were identified in 61% of the patients. Diagnostic evaluation of patients with mild to moderate cognitive symptoms and possible dementia is an integrated multidisciplinary task, which should focus on the identification of non-progressive and potentially reversible etiologies, co-morbidity, selective cognitive deficits, and rare or atypical neurological conditions, as well as on the early identification of common progressive dementia disorders.     

Potentially reversible conditions in 1000 consecutive memory clinic patients

OBJECTIVES: To investigate the prevalence and classification of potentially reversible conditions in a prospective memory clinic cohort of younger and elderly patients with cognitive symptoms. PATIENTS: 1000 consecutive patients referred during a period of 54 months to a university hospital multidisciplinary memory clinic based in neurology. METHODS: All patients were referred for diagnostic evaluation and treatment of cognitive symptoms. The multidisciplinary staff prospectively established a standardised consensus report for each patient based on the results of clinical and ancillary investigations with classification of cognitive profile, primary underlying cause, and concomitant conditions. RESULTS: The mean age of the patients was 66.1 years (range 17-98) and 43% met diagnostic criteria for dementia. A potentially reversible primary aetiology for cognitive symptoms was identified in 19% and a potentially reversible concomitant condition in 23% of all patients. In the subgroup of patients with dementia, 4% had a potentially reversible primary aetiology. Careful clinical examination, routine laboratory tests, and cranial computed tomography identified most of these conditions. CONCLUSIONS: Reversible conditions are most often encountered in patients with mild cognitive disturbances. Although treatment may not always result in full reversal of cognitive symptoms, potentially reversible conditions should be identified in the diagnostic evaluation of the patient.     

The association between psychiatric and cognitive symptoms after stroke: a prospective study

BACKGROUND: Stroke patients often have neuropsychiatric symptoms and cognitive deficits. The aim of this study was to investigate whether stroke patients with psychiatric symptoms are at increased risk of developing cognitive deficits. METHODS: Cognitive function (assessed with a neuropsychological test battery) and presence of psychiatric symptoms (assessed with the 90-item Symptom Checklist) were evaluated at 1, 6, 12 and 24 months after stroke. RESULTS: At baseline, 156 patients entered the study, 15 had a diagnosis of vascular dementia, 113 one of post-stroke mild cognitive impairment. Patients with psychiatric symptoms were found to be at increased risk of being diagnosed as having vascular dementia at baseline (OR = 6.9, CI = 1.3-36.8) and showed more decline on cognitive function 6 months after stroke. CONCLUSIONS: Patients with psychiatric symptoms after stroke are at increased risk of cognitive deficits and decline in cognitive functioning.     

Suspected dementia: evaluation of 323 consecutive referrals

A neurological outpatient department studied 323 consecutive referrals for suspected dementia: 135 (41.8%) were not demented. Of the patients 12.1% had diffuse cognitive disorder; 10.2% circumscribed memory disorder; 0.9% other circumscribed cognitive disorder, 14.2% psychiatric disorder, and 4.3% were judged to be normal. Of the nondemented, 44.1% had a potentially treatable cause for their cognitive symptoms; in 27.4% it was depression. The total of demented patients was 188 (58.2%): 38.8% had primary degenerative dementia; 37.2% vascular dementia including combined degenerative and vascular dementia; and 23.4% had a specific cause. Patients with specific cause were significantly younger than those with other causes of dementia. A potentially treatable cause was found in 10.7% of all demented patients, the most common being metabolic disorders, meningioma, hydrocephalus, subdural haematoma, and depressive pseudodementia.     

Neuropsychological profile of patients with Parkinson's disease without dementia

Cognitive deficits are often associated with Parkinson's disease (PD), although their prevalence in PD patients without dementia is still unknown. In order to describe the neuropsychological profile of PD patients without dementia, a sample of 103 PD patients was compared with a control group consisting of 38 healthy elderly subjects. Psychometric assessment consisted of the Mini Mental State Examination, the Dementia Rating Scale and a battery of neuropsychological tests. The Beck Depression Inventory was used to assess depression in PD patients. Dementia was diagnosed in 27 patients. Among non-demented subjects, 34 (45%) had no cognitive impairment and 42 (55%) had a mild cognitive impairment. Subjects with mild cognitive impairment were older, had a later onset of the disease, and more severe motor symptoms than cognitively intact subjects. Identification of mild cognitive impairment is important, since these symptoms are important for patient management and may also facilitate to determine prognosis.     

Emotional perception deficits in amyotrophic lateral sclerosis.

OBJECTIVE: Cognitive deficits associated with frontal lobe dysfunction can occur in amyotrophic lateral sclerosis (ALS), particularly in individuals with bulbar ALS who can also suffer pathologic emotional lability. Because frontal pathophysiology can alter emotional perception, we examined whether emotional perception deficits occur in ALS, and whether they are related to depressive or dementia symptoms. METHODS: Bulbar ALS participants (n=13) and age-matched healthy normal controls (n=12) completed standardized tests of facial emotional and prosodic recognition, the Geriatric Depression Scale, and the Mini-Mental State Examination. Participants identified the basic emotion (happy, sad, angry, afraid, surprised, disgusted) that matched 39 facial expressions and 28 taped, semantically neutral, intoned sentences. RESULTS: ALS patients performed significantly worse than controls on facial recognition but not on prosodic recognition. Eight of 13 patients (62%) scored below the 95% confidence interval of controls in recognizing facial emotions, and 3 of these patients (23% overall) also scored lower in prosody recognition. Among the 8 patients with emotional perceptual impairment, one-half did not have depressive, or memory or cognitive symptoms on screening, whereas the remainder showed dementia symptoms alone or together with depressive symptoms. CONCLUSIONS: Emotional recognition deficits occur in bulbar ALS, particularly with emotional facial expressions, and can arise independent of depressive and dementia symptoms or comorbid with depression and dementia. These findings expand the scope of cognitive dysfunction detected in ALS, and bolsters the view of ALS as a multisystem disorder involving cognitive and also motor deficits.     

Cerebral microhemorrhage in Marchiafava–Bignami disease detected by susceptibility-weighted imaging

Marchiafava–Bignami disease (MBD) is a rare alcohol-associated disorder. Clinical features include not only disturbed consciousness, dysarthria, tetraparesis, astasia-abasia, and symptoms of interhemispheric disconnection as initial symptoms but also cognitive deficits as clinical outcomes. The clinical significance of cerebral microhemorrhage (CMH) has been recognized in patients with cognitive deficits; however, the presence of CMH in patients with MBD has not been emphasized. The aim of the present study was to clarify the relationship between CMH and MBD. For this purpose, we report four patients with MBD, who showed asymmetrical hypointense areas in multiple cortico-subcortical regions on susceptibility-weighted imaging (SWI). All cases had a history of chronic alcohol abuse and symmetrical lesions in the entire corpus callosum. These patients’ clinical symptoms included not only coma, dysarthria, and astasia-abasia as initial symptoms but also dementia as a clinical outcome. SWI showed asymmetrical hypointense areas in the multiple cortico-subcortical regions, indicating the presence of CMH. Compared with patients with normal cognitive function, demented patients showed higher severity of CMH. Our report would indicate that CMH is an important factor indicating the severity of dementia in patients with MBD.     

Mild cognitive impairment in old-age depression is associated with increased EEG slow-wave power

Reversible dementia in geriatric depression is known to be a risk factor for irreversible dementia. Whether just mild cognitive deficits in elderly depressed patients hold a similar risk is not known yet. It may be suggested that elderly depressed patients with mild cognitive deficits, who are prone to develop dementia, show EEG alterations similar to those observed in demented patients. We studied the relationships between cognitive performance, severity of depressive symptoms and quantitative EEG parameters in 31 unmedicated, nondemented, depressed patients aged 60 years or more. Twenty-one of the patients showed a cognitive performance characteristic of mild cognitive impairment. In these patients, the mean delta and theta power was significantly higher than in the patients without cognitive impairment. Total delta power was negatively correlated with cognitive performance. There was no relationship between cognitive performance or EEG parameters and the severity of depression.     

Cognitive predictors of dementia in Parkinson's disease: a community-based, 4-year longitudinal study

Although mild cognitive impairment and dementia are common and have important clinical consequences for patients with Parkinson's disease (PD) and their caregivers, it is still unclear whether cognitive symptoms may predict the development of dementia in PD patients. The objective of this study was to determine whether cognitive deficits in nondemented PD patients predicted the development of dementia 4 years later. A total of 76 nondemented PD patients from an epidemiological study of PD in the county of Rogaland, Norway, were assessed at baseline and 4 years later with neurological, psychiatric, and neuropsychological evaluations. Twenty-five (42%) new cases of dementia were diagnosed after 4 years. Time to complete the third card of the Stroop test was the only variable that was independently associated with dementia. The authors concluded that poor performance on a test sensitive to executive dysfunction predicted later development of dementia in PD patients. This finding may have important clinical implications as a marker of subsequent development of dementia.     

Prevalence and correlates of behavioral and psychiatric symptoms in community-dwelling elders with dementia or mild cognitive impairment: the Memory and Medical Care Study

BACKGROUND: Little is known about the prevalence and correlates of behavioral and psychiatric symptoms of dementia in community-dwelling elders with dementia or mild cognitive impairment (MCI). METHODS: 512 people with Mini-Mental State Examination (MMSE) scores < 24 or a decline of at least 4 points over two administrations, and their knowledgeable informants (KIs) were enrolled in the MMCS. The classification of subjects as having dementia or MCI was based on a neuropsychological battery of four tests, not a clinical diagnostic evaluation. The sample for this study included 454 subjects (dementia n = 333; MCI n = 121) and their KIs. Demographic and health-related characteristics of subjects and KIs were obtained during KI interviews. Multivariate logistic regression was used in statistical analysis. RESULTS: Compared to dementia subjects, those classified as MCI had a lower prevalence (47.1% vs 66.1%) of any symptoms (psychosis, depression, or agitation), and of agitation (24.8% vs 45.1%). Symptoms of psychosis and depression also were less prevalent, even though differences did not reach statistical significance. In the dementia group symptoms were associated with a report of a physician's diagnosis of dementia, greater functional impairment, and a KI who was a child/child-in-law. In those with MCI, symptoms were correlated with being white, greater functional impairment, and a younger, less educated, KI. CONCLUSIONS: Psychiatric and behavioral symptoms were common in community-residing elders with cognitive impairment, but their prevalence and correlates differed by study classification as having dementia or MCI. Identifying and treating these symptoms may benefit patients with cognitive impairment and their families. Longitudinal studies on the predictors, changes in prevalence, and effectiveness of treatments for psychopathology of dementia are needed.     

Markers of cognitive decline in PD: The case for heterogeneity

Cognitive impairment is highly prevalent and has a severe negative effect on health related and perceived quality of life in Parkinson's disease (PD). It is now established that 20–40% of persons with PD will develop cognitive deficits early in the disease. Moreover, the risk of developing dementia is six times higher in PD patients than in age-matched controls and it is estimated that 80% of patients will develop dementia after 20 years of the disease. In order to address these symptoms properly it is crucial to identify very early in the disease the patients who are most likely to develop dementia rapidly. Persons who meet criteria for mild cognitive impairment (MCI) exhibit measurable cognitive deficits but those deficits are not severe enough to interfere significantly with daily life. While the presence of MCI in PD increases the chance of developing dementia, various studies suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. In this paper we comment on various biomarkers associated with cognitive decline in PD, specifically clinical, neuropathological, genetic and neuroimaging ones. We also discuss disrupted functional connectivity in PD-MCI and reveal preliminary results from our own group. We propose that the current studies looking at different types of biomarkers provide support for different causes being associated with cognitive decline in PD. Large-scale multi-disciplinary and multi-modal longitudinal studies are required to identify more specifically the different phenotypes associated with different cognitive profiles and evolution in PD.     

Dementia as a complication of schizophrenia

OBJECTIVES: Cognitive impairment is known to occur in schizophrenia, and may be marked in institutionalised patients. The aim of this study was to determine whether it ever warrants an additional diagnosis of dementia. METHODS: A population of chronic schizophrenic patients who were aged 65 or younger and showed no organic risk factors for dementia were screened for presence of disorientation. Any showing this underwent neuropsychological testing, physical investigations, and structural and functional neuroimaging. Information about day to day cognitive function was also obtained from carers. RESULTS: Eight patients aged 28 to 64 were identified who showed disorientation; in all cases this was accompanied by general intellectual impairment and objective evidence of a dementia syndrome. The patients' schizophrenic symptoms were unexceptional and did not seem sufficient to account for their cognitive impairment. Neuropsychological testing disclosed relative sparing of visual and visuospatial function and language syntax, but pervasive deficits in memory and executive function. Brain CT demonstrated only minor abnormalities but most of the patients showed frontal or temporal hypoperfusion on SPECT. CONCLUSIONS: Dementia in schizophrenia seems to be a real entity with a neuropsychological signature similar to that of frontotemporal dementia. Functional but not structural imaging abnormalities may also be characteristic.     

Autonomic and Cognitive dysfunction in Parkinson’s disease

Objective To investigate whether there is an association between autonomic failure and cognitive impairment in patients with idiopathic Parkinson’s disease (PD) Methods 40 PD patients and 30 age matched controls were assessed for cognitive and behavioral manifestations using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), the Blessed scale and Cornell scale for depression. The subjects were also assessed for orthostatic hypotension (OH), postprandial hypotension (PPH), heart rate responses to deep breathing (HR_DB) and autonomic symptoms using the Scale for Outcomes in PD for autonomic symptoms (SCOPA AUT). Results There was a correlation between the severity of motor symptoms and cognitive impairment in our PD patients. Eleven of the 40 PD patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria of dementia. The presence of OH or PPH did not correlate with the severity of cognitive impairment in our PD cases. However, PD patients with dementia reported more cardiovascular symptoms than PD patients without dementia. There was no correlation between gastrointestinal or urologic symptoms and cognitive impairment in our PD cases. Conclusion The results of this limited study indicate that despite the higher incidence of cardiovascular symptoms in PD patients with dementia than in those without dementia, there is no consistent association between OH or PPH and cognitive deficits in PD. The lack of correlation between OH, gastrointestinal and urinary symptoms with cognitive impairment suggests that cognitive and autonomic involvement progresses independently from each other and variably among PD patients.     

Mental changes in patients with AIDS

Mental changes are common in patients with acquired immunodeficiency syndrome (AIDS). Neuropsychological data of 32 patients with AIDS and cognitive symptoms were reviewed. All patients were neurologically examined and ancillary investigations were performed. According to the neuropsychological data three groups could be distinguished: I) 4 patients with dementia and cortical deficits; II) 16 patients with subcortical dementia; III) 12 patients with subcortical cognitive deficits without global intellectual deterioration. AIDS Dementia Complex (ADC) was diagnosed in 12 patients and occurred in all three groups. The most frequent form of dementia in patients with AIDS is of a subcortical type. Impaired memory or reduced psychomotor speed, or both, are common in patients without global intellectual deterioration. ADC seems an unlikely diagnosis in patients with cortical dementia. Neuropsychological examination is important for diagnosing ADC but the diagnosis cannot be made without regarding the neurological findings and ancillary investigations.     

A perspective on psychosis in late life and deficits in social cognition

The etiology of new psychotic symptoms in late life, including subtle changes in cognition, is a controversial emerging area of study. The development of psychotic symptoms, particularly paranoia, is a common occurrence in late life, and the symptoms of cognitive dysfunction and psychosis are often prominent in dementia, schizophrenia, and mood disorders. This intermixing of symptoms has inescapably led to diagnostic confusion with regard to elderly patients with new-onset psychosis. The complex relationship among different domains of psychopathology makes it difficult to tease apart disorders of affect from psychosis, affect from cognition, and psychosis from cognition. It is therefore potentially useful to modify and expand our approach to how we conceptualize these patients. Emerging evidence suggests that those with dementia, psychotic disorders, and mood disorders suffer from growing cognitive deficits. The article suggests that deficits in social cognition, in particular, may be the unifying deficit that helps to explain why heterogeneous patients may develop paranoia and psychotic symptoms in late life.     

A follow-up study of cognitive impairment due to inferior capsular genu infarction

Abulia, memory loss, other cognitive deficits, and behavioral changes consistent with dementia can follow an inferior capsular genu infarction, but only little is known about the time course of these disturbances. The present study describes the long-term outcome of cognitive defects in four patients with inferior capsular genu infarction who underwent a neuropsychological examination within 3 and 12 months of onset. Three patients had infarcts in the inferior genu of the left internal capsule and had similar symptoms in the acute phase: disorientation, memory loss, language impairment, and behavioral changes. The patient with right-side infarct showed memory impairment and behavioral changes. Three patients had deficits in one or more cognitive domains on the first assessment, but none was demented. By the second evaluation all subjects had improved. In two patients there were a moderate memory defect persisted and a language disturbance. Improvement in these disturbances during long-time follow-up demonstrates that there are alternative pathways that reestablish the functional connections damaged by the strategically located capsular genu infarct. Inferior capsular genu infarction is not a cause of persisting “strategic infarct dementia.” Received: 20 October 1998 Received in revised form: 30 December 1998 Accepted: 11 February 1999     

The rate of conversion of mild cognitive impairment to dementia: predictive role of depression

BACKGROUND: Mild cognitive impairment (MCI) is a condition referring to the persons with cognitive deficits measurable in some form or another, but not meeting criteria for dementia, and who have an increased risk of becoming demented. OBJECTIVE: To establish the rate of progression to dementia in MCI, to investigate the risk of conversion for amnestic vs multiple-domains subtypes, and to identify the predictors of progression. METHODS: MCI (n = 105) individuals enrolled in a longitudinal study received annual clinical and psychometric examinations for up to a mean of 3 years. The diagnosis of MCI according to Mayo Clinic Petersen's Criteria was conducted by a panel of specialists. RESULTS: After 3 years of follow-up, 23 of 105 subjects with MCI were diagnosed with dementia. 40 showed cognitive decline not dementia, 34 were stable and showed no cognitive decline or improvement, while eight showed cognitive improvement. CONCLUSIONS: We conclude that conversion rate from MCI to DSM-IIIR dementia was 21.9% over a period of 3 years. The occurrence of depressive symptoms may constitute a predictor for those who are more likely to progress to dementia. The risk of conversion to dementia was higher among the subjects with an evidence of impairment extending beyond memory than with those who suffered only from memory deficits, and the subjects who converted to dementia in this subtype had significantly higher baseline plasma total homocysteine levels than non-converters.     

The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis

BACKGROUND: Late-onset GM2 gangliosidosis (LGG) is a rare disease that is often considered in the differential diagnosis of adolescents and young adults who present with multiple realms of neurologic dysfunction. Cognitive disturbances are common but have not been systematically studied. OBJECTIVE: To determine the natural history of cognitive dysfunction in patients with LGG. DESIGN: Case series and literature review. SETTING: Urban tertiary referral clinic. PATIENTS: Individuals with hexosaminidase A deficiency as the origin of LGG. MAIN OUTCOME MEASURES: Cognitive dysfunction, psychiatric symptoms, and cerebellar, upper motor neuron, lower motor neuron, or extrapyramidal symptoms and signs. RESULTS: Historical and examination data from 62 patients were found. Forty-four percent of LGG patients had some degree of cognitive dysfunction. Cognitive dysfunction was associated with a greater number of other elemental neurologic deficits. In 21 patients with acceptable longitudinal information, 8 (38%) had a static cognitive disorder, whereas progressive dementia was evident in 13 patients (62%), including 2 of our cases with serial neuropsychological testing. Neuroimaging often showed nonspecific cerebellar and/or cerebral atrophy. CONCLUSIONS: Cognitive dysfunction is a frequent manifestation of LGG. Patients who experience cognitive dysfunction are more likely to have a greater number of other neurologic manifestations of the disease. Cognitive dysfunction may take the form of static encephalopathy, but progressive dementia is more often encountered. The pathogenesis of cognitive dysfunction in this disease is unknown, highlighting the need for further study.     

Essential tremor--a neurodegenerative disorder associated with cognitive defects?

In the past decade, the hypothesis that essential tremor is a monosymptomatic tremorogenic disorder has been questioned. New clinical, neuroimaging, electrophysiological and pathological studies indicate that essential tremor is associated with subtle neurological deficits and could be considered a slowly progressive neurodegenerative disorder. The aim of this Review is to describe the nonmotor neurological symptoms that are commonly associated with essential tremor, and highlight the cognitive deficits associated with this condition. Several clinical studies have demonstrated that essential tremor is associated with mild deficits in attention, executive functions, memory and, possibly, other cognitive processes. Population-based surveys have confirmed that dysfunction in these cognitive domains affects patients both with severe and mild essential tremor. Clinical studies have also indicated that cognitive deficits associated with essential tremor are progressive and that patients with this condition have an increased risk of dementia. Mood and cognitive deficits commonly observed in patients with essential tremor are similar to symptoms of cerebellar cognitive affective syndrome. Further evidence is required from prospective studies to support the interpretation that essential tremor is a slowly progressive neurodegenerative disorder.