Mild cognitive impairment: a systematic review

MCI is a nosological entity proposed as an intermediate state between normal aging and dementia. The syndrome can be divided into two broad subtypes: amnestic MCI ( aMCI) characterized by reduced memory, and non- amnestic MCI ( naMCI) in which other cognitive functions rather than memory are mostly impaired. aMCI seems to represent an early stage of AD, while the outcomes of the naMCI subtypes appear more heterogeneous - including vascular dementia, frontotemporal dementia or dementia with Lewy bodies- but this aspect is still under debate. MCI in fact represents a condition with multiple sources of heterogeneity, including clinical presentation, etiology, and prognosis. To improve classification and prognosis, there is a need for more sensitive instruments specifically developed for MCI as well as for more reliable methods to determine its progression or improvement. Current clinical criteria for MCI should be updated to include restriction in complex ADL; also the diagnostic and prognostic role of behavioral symptoms and motor dysfunctions should be better defined. A multidisciplinary diagnostic approach including biological and neuroimaging techniques may probably represent the best option to predict the conversion from MCI to dementia. In this review we discuss the most recent aspects related to the epidemiological, clinical, neuropathological, neuroimaging, biochemical and therapeutic aspects of MCI, with specific attention to possible markers of conversion to dementia

Mild behavioral impairment in Parkinson's disease: Data from the Parkinson's disease cognitive impairment study (PACOS)

Neuropsychiatric symptoms (NPS) have been frequently described in Parkinson's disease (PD), even in the earliest stages of the disease. Recently the construct of mild behavioral impairment (MBI) has been proposed as an at-risk state for incident cognitive decline and dementia. The aim of the present study is to evaluate the prevalence and associated factors of MBI in PD. Cross-sectional data from 429 consecutive PD patients enrolled in the PArkinson's disease COgnitive impairment Study (PACOS) were included in the study. All subjects underwent neuropsychological assessment, according to the MDS Level II criteria. NPS were evaluated with the Neuropsychiatric Inventory. Multivariate logistic regression models were used to evaluate clinical and behavioral characteristics, which are associated with PD-MBI. The latter was ascertained in 361 (84.1%) subjects of whom 155 (36.1%) were newly diagnosed patients (disease duration ≥1 year) and 206 (48.0%) had a disease duration <1 year. Furthermore, 68 (15.9%) out of 429 subjects were PDw (without MBI). Across the MBI domains, Impulse Dyscontrol was significantly more prevalent among PD-MBI with disease duration <1 year than newly diagnosed patients. The frequency of Social Inappropriateness and Abnormal Perception significantly increased throughout the entire PD-MBI sample with increasing Hoehn andYahr (H&Y) stages. PD-MBI in newly diagnosed PDwas significantly associated with H&Y stage (OR 2.35, 95% CI 1.05-5.24) and marginally with antidepressant drug use (OR 2.94, 95% CI 0.91-9.47), while in patients with a disease duration >1 year was associated with UPDRS-ME (OR 3.37, 95% CI 1.41-8.00). The overall MBI frequency in the PACOS sample was 84% and 36% among newly diagnosed patients. The presence of MBI mainly related to motor impairment and disability

Incidence of mild cognitive impairment and dementia in Parkinson's disease: The Parkinson's disease cognitive impairment study

Background: Cognitive impairment in Parkinson's disease (PD) includes a spectrum varying from Mild Cognitive Impairment (PD-MCI) to PD Dementia (PDD). The main aim of the present study is to evaluate the incidence of PD-MCI, its rate of progression to dementia, and to identify demographic and clinical characteristics which predict cognitive impairment in PD patients. Methods: PD patients from a large hospital-based cohort who underwent at least two comprehensive neuropsychological evaluations were retrospectively enrolled in the study. PD-MCI and PDD were diagnosed according to the Movement Disorder Society criteria. Incidence rates of PD-MCI and PDD were estimated. Clinical and demographic factors predicting PD-MCI and dementia were evaluated using Cox proportional hazard model. Results: Out of 139 enrolled PD patients, 84 were classified with normal cognition (PD-NC), while 55 (39.6%) fulfilled the diagnosis of PD-MCI at baseline. At follow-up (mean follow-up 23.5 ± 10.3 months) 28 (33.3%) of the 84 PD-NC at baseline developed MCI and 4 (4.8%) converted to PDD. The incidence rate of PD-MCI was 184.0/1000 pyar (95% CI 124.7-262.3). At multivariate analysis a negative association between education and MCI development at follow-up was observed (HR 0.37, 95% CI 0.15-0.89; p = 0.03). The incidence rate of dementia was 24.3/1000 pyar (95% CI 7.7-58.5). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD, giving an incidence rate of 123.5/1000 pyar (95% CI 70.3-202.2). A five time increased risk of PDD was found in PD patients with MCI at baseline (RR 5.09, 95% CI 1.60-21.4). Conclusion: Our study supports the relevant role of PD-MCI in predicting PDD and underlines the importance of education in reducing the risk of cognitive impairment

Clinical Evaluation of a Telemedically Linked Intraoral Drug Delivery System

The miniaturized intraoral drug delivery system BuccalDose is composed of a replaceable cartridge which is worn in a removable prosthesis and an external base station for telemedical therapy monitoring. The system has now been tested for the first time with Parkinson\u2019s disease (PD) patients. The study evaluated the usability of the entire system, the functionality of the telemedical transmission path and the functionality of the cartridge, which uses an osmotic pumping principle to release a liquid drug formulation to the buccal mucosa. The BuccalDose system was generally considered to be easy to handle, even with movement disorders, up to a mild-moderate disease stage. In addition, the obtained in vivo release rates of the cartridges confirmed the previously achieved in vitro release behavior

Cardiovascular autonomic function and MCI in Parkinson's disease

Introduction: dysautonomic dysfunction and cognitive impairment represent the most disabling non-motor features of Parkinson's Disease (PD). Recent evidences suggest the association between Orthostatic Hypotension (OH) and PD-Dementia. However, little is known on the interactions between cardiovascular dysautonomia and Mild Cognitive Impairment (MCI). We aimed to evaluate the association between cardiovascular dysautonomia and MCI in patients with PD. Methods: non-demented PD patients belonging to the PACOS cohort underwent a comprehensive instrumental neurovegetative assessment including the study of both parasympathetic and sympathetic function (30:15 ratio, Expiratory-Inspiratory ratio [E-I] and presence of Orthostatic Hypotension [OH]). Diagnosis of MCI was made according to the MDS criteria level II. Results: we enrolled 185 PD patients of whom 102 (55.1%) were men, mean age was 64.6 ± 9.7 years, mean disease duration of 5.6 ± 5.5 years with a mean UPDRS-ME score of 31.7 ± 10.9. MCI was diagnosed in 79 (42.7%) patients. OH was recorded in 52 (28.1%) patients, altered 30:15 ratio was recorded in 39 (24.1%) patients and an altered E-I ratio was found in 24 (19.1%) patients. Presence of MCI was associated with an altered 30:15 ratio (adjOR 2.83; 95%CI 1.25–6.40) but not with an altered E-I ratio, while OH was associated only with the amnestic MCI subgroup (OR 2.43; 95% CI 1.05–5.06). Conclusion: in our study sample, MCI was mainly associated with parasympathetic dysfunction in PD

Movements execution in amnestic mild cognitive impairment and Alzheimer's disease.

We evaluated the relationship between motor and neuropsychological deficits in subjects affected by amnestic Mild Cognitive Impairment (aMCI) and {early} Alzheimer's Disease (AD). Kinematics of goal-directed movement of aMCI and AD subjects were compared to those of age-matched control subjects. AD showed a slowing down of motor performance compared to aMCI and controls. No relationships were found between motor and cognitive performances in both AD and aMCI. Our results suggest that the different motor behaviour between AD and aMCI cannot be related to memory deficits, probably reflecting the initial degeneration of parietal-frontal circuits for movement planning. The onset of motor dysfunction in early AD could represent the transition from aMCI to AD

Predictors of progression from mild cognitive impairment to Alzheimer disease

OBJECTIVE: To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI). METHOD: We followed 185 persons with no cognitive impairment and 47 with MCI(amnestic and multidomain), ages 75 to 95, from the population-based Kungsholmen Project, Stockholm, Sweden, for 3 years. Three types of neuropsychiatric symptoms were assessed at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptomatology. AD at 3-year follow-up was diagnosed according to Diagnostic and Statistical Manual for Mental Disorders-III-R criteria. RESULTS: Psychiatric symptoms occurred more frequently in persons with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in cognitively intact elderly individuals (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of persons with both MCI and anxiety symptoms, 83.3% developed AD over follow-up vs 6.1% of cognitively intact persons and 40.9% persons who had MCI without anxiety. Among persons with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom (relative risk [RR] = 1.8 [1.2 to 2.7] per symptom). Conversely, among cognitively intact subjects, only symptoms of depressive mood were related to AD development (RR = 1.9 [1.0 to 3.6] per symptom). CONCLUSIONS: The predictive validity of mild cognitive impairment (MCI) for identifying future Alzheimer disease (AD) cases is improved in the presence of anxiety symptoms. Mood-related depressive symptoms (dysphoria, suicidal ideation, etc.) in preclinical AD might be related to the neuropathologic mechanism, as they appear preclinically in persons both with and without MCI

Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Products of oxidative and nitrosative stress (OS and NS, respectively) accumulate with aging, which is the main risk factor for AD. This provides the basis for the involvement of OS and NS in AD pathogenesis. OS and NS occur in biological systems due to the dysregulation of the redox balance, caused by a deficiency of antioxidants and/or the overproduction of free radicals. Free radical attack against lipids, proteins, sugars and nucleic acids leads to the formation of bioproducts whose detection in fluids and tissues represents the currently available method for assessing oxidative/nitrosative damage. Post-mortem and in-vivo studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment (MCI). In addition to their individual role, biomarkers for OS and NS in AD are associated with altered bioenergetics and amyloid-beta (Aβ) metabolism. In this review we discuss the main results obtained in the field of biomarkers of oxidative/nitrosative stress in AD and MCI in humans, in addition to their potential role as a tool for diagnosis, prognosis and treatment efficacy in AD. © 2009 Elsevier Ireland Ltd. All rights reserved

Transcranial random noise stimulation over the primary motor cortex in PD-MCI patients: a crossover, randomized, sham-controlled study

Mild cognitive impairment (MCI) is a very common non-motor feature of Parkinson’s disease (PD) and the non-amnestic single-domain is the most frequent subtype. Transcranial random noise stimulation (tRNS) is a non-invasive technique, which is capable of enhancing cortical excitability. As the main contributor to voluntary movement control, the primary motor cortex (M1) has been recently reported to be involved in higher cognitive functioning. The aim of this study is to evaluate the effects of tRNS applied over M1 in PD-MCI patients in cognitive and motor tasks. Ten PD-MCI patients, diagnosed according to the Movement Disorder Society, Level II criteria for MCI, underwent active (real) and placebo (sham) tRNS single sessions, at least 1 week apart. Patients underwent cognitive (Digit Span Forward and Backward, Digit Symbol, Visual Search, Letter Fluency, Stroop Test) and motor assessments (Unified Parkinson’s Disease Rating Scale [UPDRS-ME], specific timed trials for bradykinesia, 10-m walk and Timed up and go tests) before and after each session. A significant improvement in motor ability (UPDRS-ME and lateralized scores, ps from 0.049 to 0.003) was observed after real versus sham tRNS. On the contrary, no significant differences were found in other motor tasks and cognitive assessment both after real and sham stimulations. These results confirm that tRNS is a safe and effective tool for improving motor functioning in PD-MCI. Future studies using a multisession tRNS applied over multitargeted brain areas (i.e., dorsolateral prefrontal cortex and M1) are required to clarify the role of tRNS regarding rehabilitative intervention in PD

Cognitive impairment and levodopa induced dyskinesia in Parkinson’s disease: a longitudinal study from the PACOS cohort

Aim of the study was to evaluate possible associations between cognitive dysfunctions and development of Levodopa Induced Dyskinesia (LID). PD patients from the Parkinson’s disease Cognitive impairment Study cohort who underwent a baseline and follow-up neuropsychological evaluations were enrolled. Mild Cognitive Impairment (PD-MCI) was diagnosed according to MDS level II criteria. The following cognitive domains were evaluated: episodic memory, attention, executive function, visuo-spatial function and language. A domain was considered as impaired when the subject scored 2 standard deviation below normality cut-off values in at least one test for each domain. Levodopa equivalent dose, UPDRS-ME and LID were recorded at baseline and follow-up. To identify possible neuropsychological predictors associated with the probability of LID development at follow-up, Cox proportional-hazards regression model was used. Out of 139 PD patients enrolled (87 men, mean age 65.7 ± 9.4), 18 (12.9%) were dyskinetic at baseline. Out of 121 patients non-dyskinetic at baseline, 22 (18.1%) developed LID at follow-up. The impairment of the attention and executive domains strongly predicted the development of LID (HR 4.45;95%CI 1.49–13.23 and HR 3.46; 95%CI 1.26–9.48 respectively). Impairment of the attention and executive domains increased the risk of dyskinesia reflecting the alteration of common cortical network