Predictors of progression of cognitive decline in Alzheimer’s disease: the role of vascular and sociodemographic factors

Rates of disease progression differ among patients with Alzheimer’s disease, but little is known about prognostic predictors. The aim of the study was to assess whether sociodemographic factors, disease severity and duration, and vascular factors are prognostic predictors of cognitive decline in Alzheimer’s disease progression. We conducted a longitudinal clinical study in a specialized clinical unit for the diagnosis and treatment of dementia in Rome, Italy. A total of 154 persons with mild to moderate Alzheimer’s disease consecutively admitted to the dementia unit were included. All patients underwent extensive clinical examination by a physician at admittance and all follow-ups. We evaluated the time-dependent probability of a worsening in cognitive performance corresponding to a 5-point decrease in Mini-Mental State Examination (MMSE) score. Survival analysis was used to analyze risk of faster disease progression in relation to age, education, severity and duration of the disease, family history of dementia, hypertension, hypercholesterolemia, and type 2 diabetes. Younger and more educated persons were more likely to have faster Alzheimer’s disease progression. Vascular factors such as hypertension and hypercholesterolemia were not found to be significantly associated with disease progression. However, patients with diabetes had a 65% reduced risk of fast cognitive decline compared to Alzheimer patients without diabetes. Sociodemographic factors and diabetes predict disease progression in Alzheimer’s disease. Our findings suggest a slower disease progression in Alzheimer’s patients with diabetes. If confirmed, this result will contribute new insights into Alzheimer’s disease pathogenesis and lead to relevant suggestions for disease treatment

Predicting disease progression in alzheimer's disease: The role of neuropsychiatric syndromes on functional and cognitive decline

Patients with Alzheimer's disease (AD) have heterogeneous rates of disease progression. The aim of the current study is to investigate whether neuropsychiatric disturbances predict cognitive and functional disease progression in AD, according to failure theory. We longitudinally examined 177 memory-clinic AD outpatients (mean age = 73.1, SD = 8.1; 70.6% women). Neuropsychiatric disturbances at baseline were categorized into five syndromes. Patients were followed for up to two years to detect rapid disease progression defined as a loss of >= 1 abilities in Activities of Daily living (ADL) or a drop of >= 5 points on Mini-Mental State Examination (MMSE). Hazard ratios (HR) were calculated with Gompertz regression, adjusting for sociodemographics, baseline cognitive and functional status, and somatic comorbidities. Most patients (74.6%) exhibited one or more neuropsychiatric syndromes at baseline. The most common neuropsychiatric syndrome was Apathy (63.8%), followed by Affective (37.3%), Psychomotor (8.5%), Manic (7.9%), and Psychotic (5.6%) syndromes. The variance between the observed (Kaplen Meier) and predicted (Gompertz) decline for disease progression in cognition (0.30, CI = 0.26-0.35), was higher than the variance seen for functional decline (0.22, CI = 0.18-0.26). After multiple adjustment, patients with the Affective syndrome had an increased risk of functional decline (HR = 2.0; CI = 1.1-3.6), whereas the risk of cognitive decline was associated with the Manic (HR = 3.2, CI = 1.3-7.5) syndrome. In conclusion, specific neuropsychiatric syndromes are associated with functional and cognitive decline during the progression of AD, which may help with the long-term planning of care and treatment. These results highlight the importance of incorporating a thorough psychiatric examination in the evaluation of AD patients

Neuroendocrine features in extreme longevity

In order to evaluate the effects of some neuro-endocrine changes during aging we have studied adrenal, thyroid and pineal secretion in young, healthy old and centenarians. The number of subjects in each hormone group varied. The following parameters were evaluated: serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEAS), free triiodothyronine (FT3), thyroxine (FT4), reverse triiodothyronine (rT3) and thyroid-stimulating hormone (TSH). Urinary 6-hydroxymelatonin sulfate (aMT6s) and free cortisol were measured twice daily. Centenarians exhibited significantly lower TSH levels together with slightly higher rT3 levels than old controls. These changes could be due to reduced 50-deiodinase activity occurring also in absence of substantial changes of the nutritional pattern. Morning serum cortisol levels were found to be similar in the 3 age groups, whereas the decline of serum DHEAS levels was well evident also after the ninth decade of life. The cortisol/DHEAS molar ratio, which usually increases with age and considered to be an expression of a neurotoxic pattern of the steroidal milieu in the central nervous system, did not shown any further increase in centenarians. The urinary free cortisol and aMT6s excretion declined with age; however only in centenarians and in young controls aMT6s excretion was significantly higher at night than during the day. These findings suggest that the circadian rhythm of melatonin secretion is maintained in centenarians and, based on the limitations of this study, could be considered one factor in successful aging. 2007 Elsevier Inc. All rights reserved. Keywords: Centenarians; Melatonin; TSH; Thyroid hormones; Cortisol; DHEA-S 1. Introduction Physiological aging involves both the central nervous system [CNS] and the endocrine system. Both of these systems are essential for the maintenance of the homeostasis. Age-related changes in the CNS include progressive neuronal loss with compensatory gliosis, particularly marked in the hypothalamus, hippocampus and limbic system and imbalance among neurotransmitters and other neuro-modulatory molecules. These features may play a role in the patho-physiolog

Depressive symptoms in Parkinson's disease and in non-neurological medical illnesses

Background: Patients with neurological and non-neurological medical illnesses very often complain of depressive symptoms that are associated with cognitive and functional impairments. We compared the profile of depressive symptoms in Parkinson's disease (PD) patients with that of control subjects (CS) suffering from non-neurological medical illnesses. Methods: One-hundred PD patients and 100 CS were submitted to a structured clinical interview for identification of major depressive disorder (MDD) and minor depressive disorder (MIND), according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR), criteria. The Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) were also administered to measure depression severity. Results: When considering the whole groups, there were no differences in depressive symptom frequency between PD and CS apart from worthlessness/guilt, and changes in appetite reduced rates in PD. Further, total scores and psychic and somatic subscores of HDRS and BDI did not differ between PD and CS. After we separated PD and CS in those with MDD, MIND, and no depression (NODEP), comparing total scores and psychic/somatic subscores of HDRS and BDI, we found increased total depression severity in NODEP PD and reduced severity of the psychic symptoms of depression in MDD PD, with no differences in MIND. However, the severity of individual symptom frequency of depression was not different between PD and CS in MDD, MIND, and NODEP groups. Conclusion: Although MDD and MIND phenomenology in PD may be very similar to that of CS with non-neurological medical illnesses, neurological symptoms of PD may worsen (or confound) depression severity in patients with no formal/structured DSM-IV-TR, diagnosis of depressive mood disorders. Thus, a thorough assessment of depression in PD should take into consideration the different impacts of neurological manifestations on MDD, MIND, and NODEP. © 2013 Assogna et al, publisher and licensee Dove Medical Press Ltd

Alexithymia and anhedonia in early Richardson's syndrome and progressive supranuclear palsy with predominant parkinsonism

Phenotypic variants of progressive supranuclear palsy (PSP) are all characterized by the combination of motor symptoms of parkinsonism with a number of neuropsychiatric and cognitive disorders. Despite the strong effort in characterizing these features in PSP, alexithymia and anhedonia have not been investigated at present. Here, we aimed at investigating the qualitative and quantitative differences of alexithymia and anhedonia in the two more frequent variants of PSP, Richardson's syndrome (PSP-RS) and PSP with predominant parkinsonism (PSP-P) compared to Parkinson's disease (PD) patients recruited within 24 months after the onset of motor symptoms