Analyzing the subcortical dementia syndrome of Parkinson's disease using the RBANS.

On mental status examinations, groups of equally impaired patients with subcortical (Huntington's disease, HD; Parkinson's disease, PD) or cortical (Alzheimer's disease, AD) dementias exhibit different patterns of neuropsychological deficits. Using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), classification accuracies of 90% or greater have been reported for individual patients with AD or HD. To test the generality of the RBANS classification algorithm, we studied patients with dementia (AD and PDD) and without dementia (PDND). Classification accuracies were AD: 87%, PDD: 78%, and PDND: 39%. Comparisons of performance on subtests of the RBANS showed that all groups performed more poorly on tests that require motor skill or rapid information processing and that memory performance by the PD groups was not improved by procedures that enhance encoding and facilitate retrieval. The RBANS is useful for discriminating patterns of cognitive impairment in PD and AD, but only if the diagnosis of dementia is established independent of the RBANS test results. Cognitive slowing is not specific to subcortical dementia and current concepts of memory dysfunction in PD may require re-examination.     

Profile of dementia in a Nigerian community--types, pattern of impairment, and severity rating.

Out of 2494 subjects screened in a Nigerian community, 28 patients with dementia were identified. Alzheimer''s disease was diagnosed in 18 patients (64.3%), 16 of whom had probable Alzheimer''s disease. Eight patients (28.6%) had vascular dementia while one patient each had parkinsonism with dementia and depression with dementia. Patients with Alzheimer''s disease were significantly older, predominantly females and illiterates. Cognitive deficit commonly took the form of memory and judgment impairment while financial mismanagement was the most frequent impaired activity of daily living. More than half of the cases had mild disease on severity rating and were comprised mainly of Alzheimer''s disease subjects. These results confirm the higher frequency of Alzheimer''s disease over the other types as reported in other communities.     

Verbal memory impairment in subcortical ischemic vascular disease: A descriptive analysis in CADASIL

In the elderly, the high prevalence of Alzheimer's disease neuropathology presents a major challenge to the investigation of memory decline in common diseases such as small vessel disease. CADASIL represents a unique clinical model to determine the spectrum of memory impairment in subcortical ischemic vascular dementia (SIVD). One hundred and forty CADASIL patients underwent detailed clinical, neuropsychological and imaging analyses. The Free and Cued Selective Reminding Test was used as a measure of verbal memory. Forty-four out of 140 CADASIL patients (31.4%) presented with memory impairment according to this test. Eight out of 44 (18.2%) subjects with memory impairment matched the definition of the amnestic syndrome of hippocampal type. While alterations in spontaneous recall were related to the severity of subcortical ischemic lesions, the profile of memory impairment, particularly the sensitivity to cueing was found related to other factors such as hippocampal atrophy.     

Study of verbal working memory in patients with Parkinson's disease

The authors examined the nature of the working memory deficit in persons with Parkinson's disease (PD). Three hypotheses were tested: a limited storage capacity, an impaired executive component, and a reduction of psychomotor speed. Verbal working memory was assessed in 14 PD patients without dementia and 14 matched control participants. Participants were administered a classical verbal span test, working memory tasks that required either updating or manipulation capacities, and motor and psychomotor speed tasks. Patients' performance was comparable to that of control participants on the verbal span test. However, results on the working memory tasks indicated a deficit in manipulation with normal updating capacities. Motor and psychomotor slowing were found in the patient group, but slowing could not fully account for the impairment observed in the manipulation task. Results indicated that there is a genuine but selective working memory impairment in patients with PD.     

Mild cognitive impairment as predictor for Alzheimer's disease in clinical practice: effect of age and diagnostic criteria

BACKGROUND: We investigated whether the predictive accuracy of mild cognitive impairment (MCI) for Alzheimer-type dementia (AD) in a clinical setting is dependent on age and the definition of MCI used. METHOD: Non-demented subjects older than 40 (n=320) who attended a memory clinic of a university hospital were reassessed 5 years later for the presence of AD. MCI was diagnosed according to the criteria of amnestic MCI, mild functional impairment (MFI), ageing-associated cognitive decline (AACD), and age-associated memory impairment (AAMI). The main outcome measure was the area under the curve (AUC) of a receiver operating characteristic (ROC) curve. Analyses were conducted on the entire sample and on subgroups of subjects aged 40-54, 55-69 and 70-85 years. RESULTS: A diagnosis of AD at follow-up was made in 58 subjects. Four of them were in the 40-54 age group, 29 in the 55-69 age group and 25 in the 70-85 age group. The diagnostic accuracy in the entire sample was low to moderately high with AUCs ranging from 0.56 (AACD) to 0.75 (amnestic MCI). A good predictive accuracy with an AUC >0.80 was only observed in subjects aged 70-85 using the criteria of amnestic MCI (AUC=0.84). CONCLUSIONS: The predictive accuracy of MCI for AD is dependent on age and the definition of MCI used. The predictive accuracy is good only for amnestic MCI in subjects 70-85 years. As subjects with prodromal AD are often younger than 70, the usefulness of MCI as predictor of AD in clinical practice is limited.     

Lewy body disease: thalamic cholinergic activity related to dementia and parkinsonism

Within the spectrum of Lewy body disease cognitive impairment occurs in PD with dementia (PDD) and dementia with Lewy bodies (DLB). Although neocortical cholinergic deficits are associated with cognitive impairments in PDD and DLB, no neurochemical study has been published describing the thalamic cholinergic activity whereas the thalamus plays a major role in modulating cortical activity. Choline acetyltransferase (ChAT) activity was analyzed in reticular (Re), mediodorsal (MD) and centromedian (CM) thalamic nuclei in series of nine controls, five DLB with parkinsonism (DLB + P), five DLB without parkinsonism (DLB - P), six PD without dementia and 14 PDD cases. Significant reductions in ChAT were apparent in PDD as follows: in Re and MD nuclei compared with controls; in MD and CM nuclei compared with DLB + P; and in MD compared with PD. Increased ChAT activity was found in CM nuclei in DLB + P compared with DLB - P. These findings show that significant thalamic presynaptic cholinergic deficits occur only in cases of combined cortical and subcortical neurodegeneration in which dementia developed after prolonged parkinsonism.     

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease

Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease.     

Neuropsychological deficits and CT scan changes in elderly depressives

A number of computerized tests were used to study visual attention, memory and learning in elderly depressed patients. Impairment was found in approximately 70% of depressed patients and was seen particularly in memory and in measures of latency. Depressed patients showed equivalent impairment in short-term memory but less impairment in conditional associative learning compared to a group of patients with early dementia of the Alzheimer-type (DAT), matched for age and pre-morbid IQ. With respect to qualitative differences between depression and DAT, depressed patients showed a different pattern of errors and a consistently prolonged latency of response which was independent of delay in a delayed matching-to-sample test. On recovery from depression, although improvement was seen in most test scores, performance in measures of latency and in a number of tests of memory and learning failed to reach the level seen in a group of matched control subjects and approximately 35% of patients continued to show impairment. For the depressed patients, ventricular brain ratio (VBR) correlated with measures of slowing. In addition, in the 'recovered-depressives', VBR correlated with poor performance at high levels of task difficulty. These findings are discussed with respect to previous literature on the pattern of cognitive impairment and CT scan findings in depression.     

An implicit learning task activates medial temporal lobe in patients with Parkinson's disease

Recent studies provide evidence for an interaction between a declarative memory system, dependent on the medial temporal lobe (MTL), and a habit memory system, dependent on the basal ganglia. Using functional MRI, the authors studied this interaction when 1 system was compromised by neurological disease. Neural activity when performing a habit-learning task was compared in normal controls and subjects with Parkinson's disease (PD). Patients with PD showed less activation in the caudate nucleus and greater activation in a region of prefrontal cortex that has been associated with explicit memory retrieval. Patients with PD also showed activation of the MTL during the weather-prediction task. These findings are consistent with an interaction between memory systems of the MTL and the striatum.     

Early detection of Alzheimer's disease using the Cambridge Cognitive Examination (CAMCOG)

BACKGROUND: Dementia screening instruments, such as the Cambridge Cognitive Examination (CAMCOG), measure a variety of cognitive functions. However, memory impairment generally is the first sign of Alzheimer's disease (AD). It seems logical, therefore, to use only memory-related items for the early detection of AD. We divided the CAMCOG into a memory section and a non-memory section, and tested the hypothesis that the memory section predicts AD better than the non-memory section. We also provide normative data for both sections. METHODS: Normal subjects (N = 169) and patients with incident AD (i.e. satisfying AD criteria between 1 and 3 years from baseline: N = 25) were participants in the Amsterdam Study of the Elderly (AMSTEL), a population-based longitudinal study on cognitive decline and dementia. Patients with prevalent AD (i.e. satisfying AD criteria at baseline: N = 155) were either recruited in a memory clinic or came from AMSTEL. Normal subjects were cognitively intact at baseline and remained so for at least 3 years. The CAMCOG was administered to all subjects. AD was diagnosed by DSM-III-R criteria. RESULTS: Logistic regression analysis showed that the memory section was related to prevalent AD, whereas in multivariate analysis the non-memory section was not (after correction for the memory score and demographic characteristics). A similar analysis showed that the memory section predicted incident AD, as did a higher score on the non-memory section. The MMSE did not predict incident AD better than age alone. CONCLUSION: For the early detection of AD it is best to use the memory and non-memory sections separately instead of the total CAMCOG score.     

Neuropsychological profiles associated with subcortical white matter alterations and Parkinson's disease: implications for the diagnosis of dementia.

Despite the emergence of a number of new classification systems, the diagnosis of cerebrovascular dementia remains controversial. Also controversial is the significance of periventricular and deep white matter alterations (WMA) as seen on magnetic resonance imaging (MRI). To further clarify this issue, MRI scans were used to regroup patients clinically diagnosed with Alzheimer's disease (AD) or subcortical ischemic vascular dementia (IVD) into cohorts presenting with either little versus significant WMA on MRI. These two groups were then compared to demented patients diagnosed with idiopathic Parkinson's disease (PD) using a comprehensive neuropsychological protocol. Neuropsychological assessment failed to distinguish between patients with PD and significant WMA. By contrast, both of these patient groups exhibited disproportionate impairment on tests of executive systems functioning, whereas patients with little WMA showed greater impairment on tests of declarative memory and semantic knowledge. These findings constitute further evidence that the pattern of cognitive impairment associated with significant WMA is distinctly different when compared to AD. These results are discussed within the context of a growing body of literature suggesting that elements of the underlying neuropathologies in AD and IVD are linked. Implications for the diagnosis of dementia are also discussed.     

Memory related molecular signatures: The pivots for memory consolidation and Alzheimer's related memory decline

Age-related cognitive decline is the major cause of concern due to its 70% more incidence than dementia cases worldwide. Moreover, aging is also the major risk factor of Alzheimer's disease (AD), associated with progressive memory loss. Approx. 13 million people will have Alzheimer-related memory decline by 2050. Learning and memory is the fundamental process of brain functions. However, the mechanism for the same is still under investigation. Thus, it is critical to understand the process of memory consolidation in the brain and extrapolate its understanding to the memory decline mechanism. Research on learning and memory has identified several molecular signatures such as Protein kinase M zeta (PKMζ), Calcium/calmodulin-dependent protein kinase II (CaMKII), Brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB) and Activity-regulated cytoskeleton-associated protein (Arc) crucial for the maintenance and stabilization of long-term memory in the brain. Interestingly, memory decline in AD has also been linked to the abnormality in expressing these memory-related molecular signatures. Hence, in the present consolidated review, we explored the role of these memory-related molecular signatures in long-term memory consolidation. Additionally, the effect of amyloid-beta toxicity on these molecular signatures is discussed in detail.     

Cognitive decline in Parkinson's disease is associated with slowing of resting-state brain activity: a longitudinal study

The pathophysiological mechanisms of Parkinson's disease (PD)-related dementia (PDD) are still poorly understood. Previous studies using electroencephalography (EEG) and magnetoencephalography (MEG) have demonstrated widespread slowing of oscillatory brain activity as a neurophysiological characteristic of PD-related dementia. Here, we use MEG to longitudinally study early changes in oscillatory brain activity in initially nondemented PD patients that may be associated with cognitive decline. Using a longitudinal design, resting-state MEG recordings were performed twice at an approximate 4-year interval in 14 healthy controls and 49 PD patients. Changes in peak frequency and in relative spectral power for 10 brain regions were analyzed in relation to clinical measures of cognitive and motor function. In contrast to healthy controls, PD patients showed a slowing of the dominant peak frequency. Furthermore, analysis per frequency band revealed an increase in theta power over time, along with decreases in alpha1 and alpha2 power. In PD patients, decreasing cognitive performance was associated with increases in delta and theta power, as well as decreases in alpha1, alpha2, and gamma power, whereas increasing motor impairment was associated with a theta power increase only. The present longitudinal study revealed widespread progressive slowing of oscillatory brain activity in initially nondemented PD patients, independent of aging effects. The slowing of oscillatory brain activity strongly correlated with cognitive decline and therefore holds promise as an early marker for the development of dementia in PD.     

Recollection memory deficits in patients with major depressive disorder predicted by past depressions but not current mood state or treatment status

BACKGROUND: Neuropsychological studies have suggested that memory systems reliant on medial temporal lobe structures are impaired in patients with depression. There is less data regarding whether this impairment is specific to recollection memory systems, and whether clinical features predict impairment. This study sought to address these issues. METHOD: A computerized process-dissociation memory task was utilized to dissociate recollection and habit memory in 40 patients with past or current major depression and 40 age, sex and IQ matched non-psychiatric control subjects. The Cognitive Failures Questionnaire was used to assess patients' perceptions of day-to-day memory failures. RESULTS: Patients had impaired recollection memory (t = 4.7, P < 0.001), but no impairment in habit memory when compared to controls. Recollection memory performance was not predicted by indices of current mood state, but was predicted by self-assessments of impairment (beta = -0.33; P = 0.008) and past number of depressions (beta = -0.41; P = 0.001). There was no evidence that standard therapy with antidepressant medication either improved or worsened memory performance. CONCLUSIONS: The results confirm that patients with multiple past depressions have reduced function on recollection memory tasks, but not on habit memory performance. The memory deficits were independent of current mood state but related to past course of illness and significant enough that patients detected impairment in day-to-day memory function.     

The Epidemiology of Dementia Associated with Parkinson's Disease

Parkinson''s disease (PD) is the second most common neurodegenerative illness after Alzheimer''s disease (AD). Cognitive impairment and dementia are common features in PD and characterized by a wide range of cognitive deficits distinct from those seen in AD. Mild cognitive impairment occurs even early in PD and is associated with shorter time to dementia. The purpose of this review is to present recent findings on clinical aspects of dementia in PD and to elucidate underlying clinical and neurobiological risk factors.     

Slow-wave activity in the spectral analysis of the electroencephalogram is associated with cortical dysfunctions in patients with Alzheimer's disease

Cortical functions and slow-wave activity in the spectral analysis of the electroencephalogram (EEG) have been studied in 19 patients with Alzheimer's disease (AD), 18 patients with Parkinson's disease with dementia (PD), and 14 control subjects (C) to determine which functions are explained by their relationship of slow-wave activity. Multiple regression analyses revealed that a variance in visual functions, praxia of the hand, automatic speech, speech understanding, and retrieval from semantic memory were explained by their relationship with slow-wave activity in EEG in the AD group but not in the PD or C groups. The PD and AD groups exhibited equal cortical dysfunctions and mean amplitudes of delta activity in EEG. The cholinergic system, disrupted in AD, has been shown to be important in the regulation of neocortical electrical activity and may be associated with the processing of cortical functions.     

Effect of mild cognitive impairment on the patterns of neural activity in early Parkinson's disease

We have previously observed decreased activation of corticostriatal loops involved in planning (cognitive loop) and execution (motor loop) of a set shift in patients with early Parkinson's disease (PD) compared with control subjects. Here, we aimed to assess whether cognitive impairment in PD could drive these differences. Nondemented patients underwent a comprehensive neuropsychological evaluation and participated in our Wisconsin Card Sorting task functional magnetic resonance imaging protocol. Patients were separated into 2 groups according to the presence of mild cognitive impairment (MCI). Patients with MCI displayed reduced activity in the cognitive corticostriatal loop, which includes the caudate nucleus and prefrontal cortex while planning a set shift, whereas non-MCI patients exhibited activation patterns similar to those of healthy participants from our previous studies. Furthermore, reduced activation was observed in the premotor cortex of the MCI patients. Finally, hippocampal activity, correlated with individual memory scores, suggesting a compensatory mechanism in patients with preserved memory. These results suggest that the presence of MCI in PD affects activity in the prefrontal cortex and caudate nucleus as well as motor-related regions.     

Amnestic mild cognitive impairment: difference of memory profile in subjects who converted or did not convert to Alzheimer's disease

Episodic long-term, short-term, and implicit memory were investigated in 79 elderly subjects who fulfilled criteria for the amnestic form of mild cognitive impairment (a-MCI; i.e., by having an idiopathic amnestic disorder with absence of impairment in cognitive areas other than memory and without confounding medical or psychiatric conditions) and who developed Alzheimer's disease (AD) after 2 years as well as in 111 subjects affected by a-MCI who did not develop dementia. Results document a memory profile in a-MCI subjects characterized by preserved short-term and implicit memory and extensive impairment of episodic long-term memory. In virtually all episodic memory indexes examined (learning, forgetting, recognition abilities), a-MCI subjects who converted to AD were more severely impaired than were subjects who did not become demented. This memory profile, which closely resembles that exhibited by amnestic patients with bilateral mesial-temporal lobe lesions, confirms a precocious phase in preclinical AD characterized by selective involvement of mesial-temporal areas and worsening of the memory impairment as atrophic changes progress in hippocampal structures. In this context of pervasive episodic memory impairment, tests assessing the free recall of verbal material following a delay interval demonstrated the greater sensitivity to memory deficits of a-MCI subjects who developed AD.     

Tooth Loss May Predict Poor Cognitive Function in Community-Dwelling Adults without Dementia or Stroke: The PRESENT Project

Periodontal disease is a potential predictor of stroke and cognitive impairment. However, this association is unclear in adults aged 50 yr and above without a history of stroke or dementia. We evaluated the association between the number of teeth lost, indicating periodontal disease, and cognitive impairment in community-dwelling adults without any history of dementia or stroke. Dental examinations were performed on 438 adults older than 50 yr (315 females, mean age 63±7.8 yr; 123 males, mean age 61.5±8.5 yr) between January 2009 and December 2010. In the unadjusted analysis, odds ratios (OR) of cognitive impairment based on MMSE score were 2.46 (95% CI, 1.38-4.39) and 2.7 (95% CI, 1.57-4.64) for subjects who had lost 6-10 teeth and those who had lost more than 10 teeth, respectively, when compared with subjects who had lost 0-5 teeth. After adjusting for age, education level, hypertension, diabetes, hyperlipidemia, and smoking, the relationship remained significant (OR, 2.0; 95% CI, 1.08-3.69, P=0.027 for those with 6-10 teeth lost; OR, 2.26; 95% CI, 1.27-4.02, P=0.006 for those with more than 10 teeth lost). The number of teeth lost is correlated with cognitive impairment among community-dwelling adults aged 50 and above without any medical history of stroke or dementia.     

Recognition memory impairment in Parkinson's disease: power and meta-analyses

Contrary findings notwithstanding, the prevailing notion is that recognition memory is little affected by Parkinson's disease (PD). Both a power analysis and a meta-analysis were conducted to help clarify the degree of recognition memory deficit associated with PD. The power analysis confirmed that, in general, memory studies of PD participants have been underpowered. This analysis indicated the need to pool study results in a subsequent meta-analysis, the main finding of which was that recognition memory deficits do occur with PD. The largest deficit occurs in PD participants with dementia. Nevertheless, deficits also occur in PD participants without dementia on medication, but nondopaminergic central nervous system abnormalities are more likely to underlie this deficit than PD medication itself. Future development of a theory of cognitive dysfunction in PD should take into account these recognition memory deficits, which may increase with disease progression.