Alessia Donati

Neuroanatomical and neuropsychological features of elderly euthymic depressed patients with early- and late-onset.

BACKGROUND Whether or not cognitive impairment and brain structure changes are trait characteristics of late-life depression is still disputed. Previous studies led to conflicting data possibly because of the difference in the age of depression onset. In fact, several lines of evidence suggest that late-onset depression (LOD) is more frequently associated with neuropsychological deficits and brain pathology than early-onset depression (EOD). To date, no study explored concomitantly the cognitive profile and brain magnetic resonance imaging (MRI) patterns in euthymic EOD and LOD patients. METHOD Using a cross-sectional design, 41 remitted outpatients (30 with EOD and 11 with LOD) were compared to 30 healthy controls. Neuropsychological evaluation concerned working memory, episodic memory, processing speed, naming capacity and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. White matter hyperintensities were assessed semiquantitatively. RESULTS Both cognitive performance and brain volumes were preserved in euthymic EOD patients whereas LOD patients showed a significant reduction of episodic memory capacity and a higher rate of periventricular hyperintensities compared to both controls and EOD patients. CONCLUSION Our results support the dissociation between EOD thought to be mainly related to psychosocial factors and LOD that is characterized by increasing vascular burden and episodic memory decline.

Demyelination in Mild Cognitive Impairment Suggests Progression Path to Alzheimer’s Disease

The preclinical Alzheimers disease (AD) - amnestic mild cognitive impairment (MCI) - is manifested by phenotypes classified into exclusively memory (single-domain) MCI (sMCI) and multiple-domain MCI (mMCI). We suggest that typical MCI-to-AD progression occurs through the sMCI-to-mMCI sequence as a result of the extension of initial pathological processes. To support this hypothesis, we assess myelin content with a Magnetization Transfer Ratio (MTR) in 21 sMCI and 21 mMCI patients and in 42 age-, sex-, and education-matched controls. A conjunction analysis revealed MTR reduction shared by sMCI and mMCI groups in the medial temporal lobe and posterior structures including white matter (WM: splenium, posterior corona radiata) and gray matter (GM: hippocampus; parahippocampal and lingual gyri). A disjunction analysis showed the spread of demyelination to prefrontal WM and insula GM in executive mMCI. Our findings suggest that demyelination starts in the structures affected by neurofibrillary pathology; its presence correlates with the clinical picture and indicates the method of MCI-to-AD progression. In vivo staging of preclinical AD can be developed in terms of WM/GM demyelination.

Personality Traits and Behavioural and Psychological Symptoms in Patients with Mild Cognitive Impairment

Background and Aims: Both personality changes and behavioural and psychological symptoms (BPS) may be associated with mild cognitive impairment (MCI) in later life and help identify incipient dementia. We wished to investigate the links between personality and BPS in MCI. Method: We studied premorbid personality traits as estimated 5 years back and their changes in 83 control subjects and 52 MCI patients using the revised NEO Personality Inventory for the Five-Factor Model completed by a proxy. Information on BPS was obtained using the Neuropsychiatric Inventory (NPI). Analyses were controlled for current depression and anxiety. Results: Premorbid neuroticism and openness to experience were associated with the total NPI score. The changes in neuroticism, extraversion, openness to experiences, and conscientiousness were associated with apathy and affective symptoms. Conclusions: Personality changes and BPS occur in MCI. The occurrence of affective BPS and apathy is associated with both premorbid personality traits and their changes.

Subjective cognitive decline in patients with mild cognitive impairment and healthy older adults: association with personality traits.

In normal aging, subjective cognitive decline (SCD) might reflect personality traits or affective states rather than objective cognitive decline. However, little is known on the correlates of SCD in mild cognitive impairment (MCI). The present study investigates SCD in MCI patients and healthy older adults, and explores the association of SCD with personality traits, affective states, behavioral and psychological symptoms (BPS), and episodic memory in patients with MCI as compared with healthy older adults.

A multi-contrast MRI study of microstructural brain damage in patients with mild cognitive impairment

Objectives The aim of this study was to investigate pathological mechanisms underlying brain tissue alterations in mild cognitive impairment (MCI) using multi-contrast 3 T magnetic resonance imaging (MRI). Methods Forty-two MCI patients and 77 healthy controls (HC) underwent T1/T2* relaxometry as well as Magnetization Transfer (MT) MRI. Between-groups comparisons in MRI metrics were performed using permutation-based tests. Using MRI data, a generalized linear model (GLM) was computed to predict clinical performance and a support-vector machine (SVM) classification was used to classify MCI and HC subjects. Results Multi-parametric MRI data showed microstructural brain alterations in MCI patients vs HC that might be interpreted as: (i) a broad loss of myelin/cellular proteins and tissue microstructure in the hippocampus (p ≤ 0.01) and global white matter (p < 0.05); and (ii) iron accumulation in the pallidus nucleus (p ≤ 0.05). MRI metrics accurately predicted memory and executive performances in patients (p ≤ 0.005). SVM classification reached an accuracy of 75% to separate MCI and HC, and performed best using both volumes and T1/T2*/MT metrics. Conclusion Multi-contrast MRI appears to be a promising approach to infer pathophysiological mechanisms leading to brain tissue alterations in MCI. Likewise, parametric MRI data provide powerful correlates of cognitive deficits and improve automatic disease classification based on morphometric features.

The Evolution of Personality in Patients with Mild Cognitive Impairment

Aims: To describe personality traits and their changes in mild cognitive impairment (MCI) and control subjects. Methods: Sixty-three MCI and 90 control subjects were asked to describe their current personality traits by the Structured Interview for the Five-Factor Model (SIFFM). For each subject, a close relative retrospectively assessed these descriptions both as to the previous and current personality traits, using the Revised NEO Personality Inventory, Form R (NEO-PI-R). Results: Self-assessed MCI subjects reported significantly lower scores in the openness dimension than control subjects [F(1, 150) = 9.84, p = 0.002, ηp2 = 0.06]. In current observer ratings, MCI subjects had higher scores on neuroticism [F(1, 137) = 7.55, p = 0.007, ηp2 = 0.05] and lower ones on extraversion [F(1, 137) = 6.40, p = 0.013, ηp2 = 0.04], openness [F(1, 137) = 9.93, p = 0.002, ηp2 = 0.07], agreeableness [F(1, 137) = 10.18, p = 0.002, ηp2 = 0.07] and conscientiousness [F(1, 137) = 25.96, p < 0.001, ηp2 = 0.16]. Previous personality traits discriminated the groups as previous openness [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, p = 0.014] and conscientiousness (OR = 0.96, 95% CI 0.94-0.98, p = 0.001) were negatively related to MCI group membership. In MCI subjects, conscientiousness [F(1, 137) = 19.20, p < 0.001, ηp2 = 0.12] and extraversion [F(1, 137) = 22.27, p < 0.001, ηp2 = 0.14] decreased between previous and current evaluations and neuroticism increased [F(1, 137) = 22.23, p < 0.001, ηp2 = 0.14], whereas no significant change was found in control subjects. Conclusions: MCI subjects undergo significant personality changes. Thus, personality assessment may aid the early detection of dementia.

Behavioral and psychological symptoms and cognitive decline in patients with amnestic MCI and mild AD: a two-year follow-up study

BACKGROUND Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and dementia. In many cases, MCI represents an early stage of developing cognitive impairment. Patients diagnosed with MCI do not meet the criteria for dementia as their general intellect and everyday activities are preserved, although minor changes in instrumental activities of daily living (ADL) may occur. However, they may exhibit significant behavioral and psychological signs and symptoms (BPS), also frequently observed in patients with Alzheimers disease (AD). Hence, we wondered to what extent specific BPS are associated with cognitive decline in participants with MCI or AD. METHODS Our sample consisted of 164 participants, including 46 patients with amnestic (single or multi-domain) MCI and 54 patients with AD, as well as 64 control participants without cognitive disorders. Global cognitive performance, BPS, and ADL were assessed using validated clinical methods at baseline and at two-year follow-up. RESULTS The BPS variability over the follow-up period was more pronounced in the MCI group than in patients with AD: some BPS improve, others occur newly or worsen, while others still remain unchanged. Moreover, specific changes in BPS were associated with a rapid deterioration of the global cognitive level in MCI patients. In particular, an increase of euphoria, eating disorders, and aberrant motor behavior, as well as worsened sleep quality, predicted a decline in cognitive functioning. CONCLUSIONS Our findings confirm a higher variability of BPS over time in the MCI group than in AD patients. Moreover, our results provide evidence of associations between specific BPS and cognitive decline in the MCI group that might suggest a risk of conversion of individuals with amnestic MCI to AD.

RELATIONSHIPS BETWEEN PERSONALITY CHARACTERISTICS AND CSF BIOMARKERS OF ALZHEIMER'S PATHOLOGY

eGFR, mean (6SD) 68.4 (18.9, 66.9 – 69.2) 36.3 (7.1, 34.6 – 38.1) 53.3 (3.7, 45.1 – 58.1) 78.6 (13.4, 77.4 – 79.9) Age, mean (6SD) 79.2 (5.6) 82.0 (6.1, 80.5 – 83.5) 80.2 (5.5, 79.3 – 81.1) 79.3 (5.3, 78.8 – 79.8) .000 Sex, males (%) 253 (39) 28 (11) 45 (18) 180 (71) .031 Females (%) 396 (61) 39 (10) 106 (27) 251 (63) Ethnicity (%) 649 67 151 431 .035 Caucasian 440 43 92 305 Black 174 19 54 101 Hispanic, White 18 2 2 14 Hispanic, Black 7 1 3 3 Asian 5 0 0 5 Other 5 2 0 3 Years in Education 14.1 (3.4, 13.8 – 14.3) 12.6 (3.3, 12.1 – 13.7) 14.3 (3.4, 13.7 – 14.8) 14.2 (14.2, 13.8 – 14.5) .016