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Authors: Palmer, Katie | Lupo, Federica | Perri, Roberta | Salamone, Giovanna | Fadda, Lucia | Caltagirone, Carlo | Musicco, Massimo | Cravello, Luca

Article Type: Research Article

Abstract: 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. Show more

Keywords: Activities of daily living, anxiety, apathy, behavioral and psychological symptoms of dementia, failure theory, cognitive impairment, dementia, depression, disease progression, Gompertz

DOI: 10.3233/JAD-2010-101836

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 35-45, 2011

Authors: Bonnì, Sonia | Lupo, Federica | Lo Gerfo, Emanuele | Martorana, Alessandro | Perri, Roberta | Caltagirone, Carlo | Koch, Giacomo

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is characterized by altered functional cortico-cortical connectivity likely due to loss of afferent and efferent connections between different cortical areas. Here we explored parieto-frontal functional connectivity in 15 AD patients and 12 healthy control subjects by means of bifocal transcranial magnetic stimulation (TMS). Conditioning stimuli were applied over the right posterior parietal cortex (PPC) at different intensities (90% and 110% of resting motor threshold, RMT). Motor evoked potentials (MEPs) were then recorded from the ipsilateral primary motor cortex at different interstimulus intervals (ISIs) ranging between 2 and 15 ms. Results showed that in healthy subjects, a conditioning …TMS pulse applied over the ipsilateral PPC at 90%, but not at 110%, of RMT intensity was able to increase the excitability of the right M1. This functional interaction peaked at ISI = 6 ms. Conversely, in AD patients the facilitatory pattern of parieto-motor connections was evident only when TMS was delivered at an intensity of 110% of RMT with a peak at ISI = 8 ms. Moreover in AD patients, treatment with cholinesterase inhibitors did not induce any significant modification in the strength of the connection. In subsequent analyses, we found that, in AD patients, the effects induced by PPC conditioning at 110% RMT correlated with neuropsychological measures of episodic memory and executive functions, implying that patients with better cognitive performance had less impaired connectivity. Our findings reveal that parieto-frontal cortico-cortical functional connectivity is altered in AD patients, providing further evidence for a disconnection-based interpretation of AD symptoms. Show more

Keywords: Alzheimer's disease, connectivity, parietal cortex, transcranial magnetic stimulation

DOI: 10.3233/JAD-2012-121144

Citation: Journal of Alzheimer's Disease, vol. 33, no. 2, pp. 525-533, 2013