Anosognosia in mild cognitive impairment and mild Alzheimer's disease: frequency and neuropsychological correlates.

OBJECTIVES: To evaluate severity of anosognosia and to identify its neuropsychological correlates in preclinical and clinical Alzheimer's Disease (AD). METHODS: The Clinical Insight Rating Scale, the Anosognosia Questionnaire for Dementia (AQ-D), and the Mental Deterioration Battery were used to assess anosognosia and cognitive performances in mild AD (N = 38), amnesic mild cognitive impairment (a-MCI; N = 35), and multiple domain MCI (md-MCI; N = 38). RESULTS: Patients with mild AD were more anosognosic than both MCI groups, which, however, did not differ from one other. A categorical diagnosis of anosognosia was made in 42% of patients with mild AD, 3% of md-MCI, but in no subjects with a-MCI. Reduced verbal episodic memory raw score was associated with decreased awareness of cognitive difficulties (AQ-D total and intellectual functioning scores) only in MCI. In mild AD, anosognosia was linked only to increased age and reduced basic activities of daily living performances. CONCLUSIONS: The diagnosis of anosognosia is frequent in patients with mild AD but not in those with MCI. In the latter case, the authors cannot speak of true anosognosia but only of decreased awareness of illness. Furthermore, reduced awareness of cognitive difficulties is linked with verbal memory performances in patients with MCI but not in those with AD, suggesting for the latter the involvement of factors other than neuropsychological. Thus, neuropsychiatric dimensions commonly present in patients with AD should be investigated along with anosognosia.

Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer's disease and mild cognitive impairment subtypes.

BACKGROUND: Neuropsychiatric disorders are common in cognitively impaired older persons, and associated with institutionalization and caregiver stress in Alzheimer's disease (AD). Few studies have compared the occurrence of both psychiatric disorders and neuropsychiatric symptoms in patients with AD and mild cognitive impairment (MCI) subtypes. We aimed to investigate the frequency of psychiatric disorders and neuropsychiatric symptoms in AD and MCI patients, compared to controls. METHODS: We included 245 outpatients of a memory clinic in Rome, Italy (119 AD; 68 multidomain-MCI; 58 amnestic-MCI) and 107 controls. Categorical disorders of depression and apathy were diagnosed with structured interviews. Symptoms were evaluated with the Neuropsychiatric Inventory (NPI). The odds ratios (OR) of patients having neuropsychiatric symptoms compared to controls were calculated with logistic regression, adjusted for sociodemographic and clinical variables. RESULTS: A large proportion of AD (49.6%) and multidomain-MCI (44.1%) patients had depression disorder. Apathy disorder was common in AD (51.3%) but less frequent in amnestic-MCI (6.9%) and multidomain-MCI (14.7%). AD patients were three times more likely to have depression disorders (OR = 3.0, CI = 1.1-7.6) or apathy (OR = 16.9, CI = 4.6-61.8) compared to amnestic-MCI, and seven times more likely to have apathy disorder than multidomain-MCI (OR = 7.5, CI = 3.0-19.2). After apathy and depression, the most prevalent neuropsychiatric symptoms in AD and MCI were anxiety, agitation, irritability, night-time behaviors, and appetite disturbances. There was an increasing prevalence of many neuropsychiatric symptoms with increasing severity of cognitive syndromes. CONCLUSIONS: Clinicians should consider the relevance of neuropsychiatric disorders and symptoms in patients with cognitive disturbances, and incorporate a thorough psychiatric examination in the evaluation of patients.

Homotaurine Effects on Hippocampal Volume Loss and Episodic Memory in Amnestic Mild Cognitive Impairment.

Homotaurine supplementation may have a positive effect on early Alzheimer's disease. Here, we investigated its potential neuroprotective effect on the hippocampus structure and episodic memory performances in amnestic mild cognitive impairment (aMCI). Neuropsychological, clinical, and neuroimaging assessment in 11 treated and 22 untreated patients were performed at baseline and after 1 year. Magnetic resonance data were analyzed using voxel-based morphometry to explore significant differences (Family Wise Error corrected) between the two groups over time. Patients treated with homotaurine showed decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex which was associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI has a positive effect on hippocampus atrophy and episodic memory loss. Future studies should further clarify the mechanisms of its effects on brain morphometry.

Prevalence of non-dementing cognitive disturbances and their association with vascular risk factors in an elderly population.

To assess the prevalence of "Cognitive Impairment No Dementia" (CIND) and circumscribed memory impairment (CMI) and to evaluate their association with vascular risk factors and stroke, we examined all people aged 65 years or over living in three rural Italian villages. The survey was conducted by means of a doorto-door 2-phase procedure. As phase 1 screening tests, we used the Mini-Mental State Examination (MMSE), or the Mental Status Questionnaire (MSQ) for people with < 3 years of schooling. In phase 2, four neurologists examined people with MMSE scores < 28 or MSQ scores < 10. The diagnostic study consisted of a clinical and neuropsychological examination which included a structured interview with a close respondent. Dementia was diagnosed by means of DSM III-R criteria. The study protocol was completed by 968 (84.4%) of the 1147 eligible people. Of the 968 participants, 690 (71.3 %) had no cognitive abnormalities, 78 (8.1%) were demented and 200 (20.6 %) suffered from CIND. The CIND group included 59 people (6.1% of the study population) with CMI. At the multiple logistic regression analysis, CIND was associated with age >or= 75 years (OR 1.6, 95 % CI 1.1.-2.2), < 5 years of schooling (OR 3.7, 95% CI 2.5.-5.5), stroke (OR 3.3, 95% CI 1.8.-6.1) and hypertension (OR 2.3, 95% CI 1.5.-3.5),while CMI was associated with < 5 years of schooling (OR 3.8, 95 % CI 1.9.-7.7), stroke (OR 3.1, 95% CI 1.2.-7.9) and hypertension (OR 3.7, 95% CI 1.7.-8.0). Using normotensive people as a reference group and adjusting for age, sex, education and stroke, the ORs for CIND were 1.9 (95 % CI 1.2.-3.0) for treated and 2.9 (95 % CI 1.8.-4.6) for untreated hypertensive patients. In conclusion, hypertension is significantly and independently associated with both CIND and CMI, and the risk of CIND is higher in untreated than treated hypertensive patients.

The role of persistent and incident major depression on rate of cognitive deterioration in newly diagnosed Alzheimer's disease patients.

Depression may potentially impair the clinical course of Alzheimer's disease (AD). Thus, the aim of this study was to investigate cognitive progression of AD patients with or without major depressive episode (MDE). In this 1-year longitudinal follow-up study conducted in three Italian memory clinics, 119 newly diagnosed probable AD patients of mild severity, who were not undergoing treatment with an acetyl-cholinesterase inhibitor (AChEI), and had not been treated with psychotropic drugs in the last 2 years, were included. Patients were assessed to investigate the effect of baseline and 1-year follow-up MDE (using modified DSM-IV diagnostic criteria for MDE in AD) on progression of global cognitive deterioration (using Mini-Mental State Examination (MMSE)), adjusted for confounding factors. Never being depressed was associated with a 3.1 (95%CI 1.0-10.1) increased risk of MMSE decline compared to recovered depression. Six times more patients with persistent depression had MMSE decline compared to patients with recovered depression. However, the largest odds (7.3; 95%CI 1.4-38.1) of cognitive decline was observed in patients who developed incident depression over follow-up. In conclusion, persistent or incident depression worsens cognitive outcome while no or recovered depression does not affect it in early AD patients.

T cell response to amyloid-beta and to mitochondrial antigens in Alzheimer's disease.

Despite the vast amount of literature on non-specific immune mechanisms in Alzheimer's disease (AD), little is known about the role of antigen-specific immune responses. We investigated T cell reactivity to fragment 1-42 of amyloid-beta (Abeta) and to N-terminal peptides of human mitochondrial and control microbial proteins. Thirty subjects with a diagnosis of probable AD according to NINCDS-ADRDA criteria and 30 sex- and age-matched healthy controls were enrolled. T cell responses to Abeta fragment showed no significant differences between AD patients and controls. By contrast, the mean number of positive T cell responses to both human mitochondrial and microbial peptides was significantly decreased in AD patients compared to control subjects. No significant correlation was found between T cell responses and both the severity of cognitive impairment and duration of the disease. Our results suggest that antigen-specific immune responses are impaired in AD. Protective immune responses to harmful amyloidogenic substances may also be impaired, thus favoring their accumulation in the brain.