Carla Pettenati - Academia.edu (original) (raw)
Papers by Carla Pettenati
PubMed, 2005
The efficacy of medical interventions is their capacity of inducing positive modifications of the... more The efficacy of medical interventions is their capacity of inducing positive modifications of the natural history of diseases. The natural history of dementia is marked by specific events related to the cognitive and functional decline, but their occurrence is poorly predictable in individual patients being highly variable from patient to patient. For this reason it is difficult that the modest efficacy of available interventions for dementia, or their entity measured by clinical scales, may be perceived in clinical practice or in observational studies. Moreover in randomized clinical studies, the effect of this variability, in analogy to misclassification of exposition and/or disease in case control or cohort epidemiological studies, is that of an underestimation of the true efficacy of interventions.
PubMed, Nov 4, 1998
In this paper we review some theories about the process of senescence and death, in particular th... more In this paper we review some theories about the process of senescence and death, in particular the theory of accumulation of mutations and the theory of antagonistic pleiotropism. These theories are reviewed in the light of existing scientific evidence, with particular reference to that which points to the possible role of interactions between genes and environment. We conclude that mortality studies, particularly on migrant populations may be an important tool for clarifying this major issue.
Dementia and Geriatric Cognitive Disorders, 2011
tients prescribed antipsychotic drugs had a higher risk of death. This risk was highest for those... more tients prescribed antipsychotic drugs had a higher risk of death. This risk was highest for those prescribed conventional antipsychotics. At least part of the excess mortality may be due to the underlying neuropsychiatric symptoms that prompted the use of antipsychotics rather than a direct medication effect.
American Journal of Geriatric Psychiatry, Nov 1, 2010
Objectives: Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatme... more Objectives: Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Design: Cross-sectional, multicenter, clinical study. Participants: A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. Measurements: All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Results: Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N ϭ 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N ϭ 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. Conclusions: The authors' study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms.
Journal of the Neurological Sciences, Oct 1, 2009
problems 68 (56%) were identified as delayed language while 53 (44%) had aphasia. Out of 89 patie... more problems 68 (56%) were identified as delayed language while 53 (44%) had aphasia. Out of 89 patients with speech problems 15 (17%) patients had voice problems, 22 (24%) had articulation problems and 41 (47%) had fluency problems while only 11 (12%) patients had dysarthria. Conclusion: This study revealed that language problems are higher as compare to speech problems. In the domain of language problems delayed language problems are more common than aphasia. Moreover fluency problems are highest among all speech problems.
Alzheimer Disease & Associated Disorders, 2018
Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's... more Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's Diseases (AD/PD) and vice-versa. We evaluated whether a different distribution of known nongenetic risk factors for cancer and AD/PD, might explain their inverse relationship of occurrence. We nested 2 case-control studies in a subsample of a large cohort of 1,000,000 resident in Lombardy Region in Italy (n = 1515), followed-up for cancer and AD/PD occurrence since 1991 until 2012. Conditional logistic regression was performed to determine the odds ratios (OR) and 95% confidence intervals (CI) of AD/PD in subjects with and without cancer and the risk of cancer in those with and without AD/PD. A total of 54 incident cases of AD/PD and 347 cancer cases were matched with 216 and 667 controls, respectively. After controlling for low education, obesity, history of hypertension, diabetes, dyslipidemia, physical activity, smoking habit, alcohol consumption, and dietary habit, cancer was found inversely associated with the risk of AD/PD (OR, 0.66; 95% CI, 0.32-1.38), and the risk of cancer in AD/PD was similarly reduced (OR, 0.42; 95% CI, 0.20-0.91). Different exposures to nongenetic risk factors of both diseases do not explain their competitive relationship of occurrence.
Rivista di neurologia, 2002
Alzheimer disease and associated disorders, Jan 8, 2017
Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkins... more Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's Diseases (AD/PD) and vice-versa. We evaluated whether a different distribution of known nongenetic risk factors for cancer and AD/PD, might explain their inverse relationship of occurrence. We nested 2 case-control studies in a subsample of a large cohort of 1,000,000 resident in Lombardy Region in Italy (n=1515), followed-up for cancer and AD/PD occurrence since 1991 until 2012. Conditional logistic regression was performed to determine the odds ratios (OR) and 95% confidence intervals (CI) of AD/PD in subjects with and without cancer and the risk of cancer in those with and without AD/PD. A total of 54 incident cases of AD/PD and 347 cancer cases were matched with 216 and 667 controls, respectively. After controlling for low education, obesity, history of hypertension, diabetes, dyslipidemia, physical activity, smoking habit, alcohol consumption, and dietary habit, cancer was ...
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2010
Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both ... more Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Cross-sectional, multicenter, clinical study. A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxie...
Therapeutics and clinical risk management, 2007
Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressi... more Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and functional abilities associated with various behavioral disturbances. Its impact on public health and society as a whole is devastating. Slowing of the cognitive impairment, and improvements in disease duration, self-sufficiency and behavioral disturbances represent the best outcomes of pharmacologic therapy. Cholinesterase inhibitors (ChE-I) have been shown to be effective in treating the cognitive, behavioral, and functional deficits of AD. Rivastigmine is a dual inhibitor of both acetylcholine esterase (AChE) and butyrylcholinesterase (BuChE), enzymes involved in the hydrolysis of acetylcholine. Although this drug has been shown to be beneficial in patients with AD, its benefits are limited and their long-term effectiveness has not been well demonstrated.
Annali dell'Istituto superiore di sanità, 2005
The efficacy of medical interventions is their capacity of inducing positive modifications of the... more The efficacy of medical interventions is their capacity of inducing positive modifications of the natural history of diseases. The natural history of dementia is marked by specific events related to the cognitive and functional decline, but their occurrence is poorly predictable in individual patients being highly variable from patient to patient. For this reason it is difficult that the modest efficacy of available interventions for dementia, or their entity measured by clinical scales, may be perceived in clinical practice or in observational studies. Moreover in randomized clinical studies, the effect of this variability, in analogy to misclassification of exposition and/or disease in case control or cohort epidemiological studies, is that of an underestimation of the true efficacy of interventions.
Functional neurology
In this paper we review some theories about the process of senescence and death, in particular th... more In this paper we review some theories about the process of senescence and death, in particular the theory of accumulation of mutations and the theory of antagonistic pleiotropism. These theories are reviewed in the light of existing scientific evidence, with particular reference to that which points to the possible role of interactions between genes and environment. We conclude that mortality studies, particularly on migrant populations may be an important tool for clarifying this major issue.
Advances in Alzheimer's Disease, 2013
Objective: As the literature on conventional criteria for discriminating early-onset (EO) from la... more Objective: As the literature on conventional criteria for discriminating early-onset (EO) from late-onset (LO) Alzheimer's disease (AD) is sparse and controversial, the aim of this study was to establish a precise age at onset (AAO) criterion, by using a specific statistical procedure, and to describe the clinical characteristics of the two subgroups. Methods: Admixture analysis was performed to establish the AAO cutoff in a multi-center study including 2000 AD patients consecutively recruited in eight Italian Memory Clinics. None of the patients were taking acetylcholinesterase inhibitors, antipsychotic or anti-depressant drugs. At the first diagnostic visit, they were administered the Mini Mental State Examination, the Basic and Instrumental Activities of Daily Living and the Neuropsychiatric Inventory to assess clinical phenomenology. Results: Using a specific statistical procedure, we established that AAO that discriminated EOfrom LOAD was 66. Compared with the LOAD group, the EO-AD group showed longer duration of illness and a higher educational level as well as less severe functional impairment and delusions. Conclusions: Differences in sociodemographic and clinical characteristics, such as duration of illness, education and delusion severity, suggested the involvement of different pathogenic processes. Additional studies are needed to further investigate the mechanisms underlying the disorder in the two subgroups of AD patients.
Neurobiology of Aging, 2012
Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degenerati... more Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degeneration (FTLD) by haploinsufficiency mechanism, although their effects on brain tissue dysfunction and damage still remain to be clarified. In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the DMN. Our findings suggest that compensatory mechanisms of brain plasticity are present in GRN-related FTLD, but with different patterns at a preclinical and symptomatic disease stage.
Neuropsychologia, 2003
The breakdown of semantic knowledge relative to living and non-living categories was studied in p... more The breakdown of semantic knowledge relative to living and non-living categories was studied in patients with Alzheimer's disease (AD). The same living and non-living items were used in a semantic battery and in a semantic priming paradigm exploring automatic access to the semantic system. Although AD patients showed a semantic deficit on the intentional semantic battery, they demonstrated normal semantic facilitation on the priming task. In the AD group as a whole, the semantic impairment did not preferentially affect the living category either in the intentional or automatic condition. Instead, a prevalent deficit for the living category was found in three AD patients (14% of the group) on the intentional semantic tasks, but not on the automatic one. These findings support the view that the category effect may not be a generalised phenomenon in AD but may be restricted to a limited number of patients. The intentional/automatic dissociation of the semantic breakdown demonstrated by AD patients is discussed in relation to different theories regarding the organisation of semantic memory.
Riassunto. - L'efficacia degli interventi è definibile, in medicina, come la loro capacità d... more Riassunto. - L'efficacia degli interventi è definibile, in medicina, come la loro capacità di modificare positivamente la storia naturale delle malattie. La storia naturale delle demenze è contrassegnata da eventi conseguenti dal declino cognitivo e funzionale che caratterizza queste malattie. Questi eventi sono poco prevedibili nel singolo paziente dato che la loro occorrenza, o entità percepita attraverso le scale di misurazione, è largamente variabile da paziente a paziente. Ne consegue che l'efficacia dei trattamenti, modesta per quelli oggi disponibili, è difficilmente apprezzabile nella pratica clinica e persino negli studi osservazionali. Negli studi clinici randomizzati l'effetto di tale variabilità è infine analogo a quello della mis - classificazione in studi epidemiologici caso-controllo o di coorte e causa una sottostima dell'effettiva efficacia dei trattamenti. Parole chiave: demenza, scale cliniche, studi randomizzati e controllati. S u m m a ry ( V...
Neurology, 2013
Objective: To evaluate the incidence of cancer in persons with Alzheimer disease (AD) and the inc... more Objective: To evaluate the incidence of cancer in persons with Alzheimer disease (AD) and the incidence of AD dementia in persons with cancer. Methods: This was a cohort study in Northern Italy on more than 1 million residents. Cancer incidence was derived from the local health authority (ASL-Mi1) tumor registry and AD dementia incidence from registries of drug prescriptions, hospitalizations, and payment exemptions. Expected cases of AD dementia were calculated by applying the age-, sex-, and calendar year-specific incidence rates observed in the whole population to the subgroup constituted of persons with newly diagnosed cancers during the observation period (2004-2009). The same calculations were carried out for cancers in patients with AD dementia. Separate analyses were carried out for the time period preceding or following the index diagnosis for survivors and nonsurvivors until the end of 2009 and for different types and sites of cancer. Results: The risk of cancer in patients with AD dementia was halved, and the risk of AD dementia in patients with cancer was 35% reduced. This relationship was observed in almost all subgroup analyses, suggesting that some anticipated potential confounding factors did not significantly influence the results. Conclusions: The occurrence of both cancer and AD dementia increases exponentially with age, but with an inverse relationship; older persons with cancer have a reduced risk of AD dementia and vice versa. As AD dementia and cancer are negative hallmarks of aging and senescence, we suggest that AD dementia, cancer, and senescence could be manifestations of a unique phenomenon related to human aging. Neurology â 2013;81:322-328 GLOSSARY AD 5 Alzheimer disease; CI 5 confidence interval; ICD-10 5 International Classification of Diseases, 10th revision; RR 5 relative risk.
Neurobiology of Aging, 2000
Journal of the Neurological Sciences, 2009
problems 68 (56%) were identified as delayed language while 53 (44%) had aphasia. Out of 89 patie... more problems 68 (56%) were identified as delayed language while 53 (44%) had aphasia. Out of 89 patients with speech problems 15 (17%) patients had voice problems, 22 (24%) had articulation problems and 41 (47%) had fluency problems while only 11 (12%) patients had dysarthria. Conclusion: This study revealed that language problems are higher as compare to speech problems. In the domain of language problems delayed language problems are more common than aphasia. Moreover fluency problems are highest among all speech problems.
PubMed, 2005
The efficacy of medical interventions is their capacity of inducing positive modifications of the... more The efficacy of medical interventions is their capacity of inducing positive modifications of the natural history of diseases. The natural history of dementia is marked by specific events related to the cognitive and functional decline, but their occurrence is poorly predictable in individual patients being highly variable from patient to patient. For this reason it is difficult that the modest efficacy of available interventions for dementia, or their entity measured by clinical scales, may be perceived in clinical practice or in observational studies. Moreover in randomized clinical studies, the effect of this variability, in analogy to misclassification of exposition and/or disease in case control or cohort epidemiological studies, is that of an underestimation of the true efficacy of interventions.
PubMed, Nov 4, 1998
In this paper we review some theories about the process of senescence and death, in particular th... more In this paper we review some theories about the process of senescence and death, in particular the theory of accumulation of mutations and the theory of antagonistic pleiotropism. These theories are reviewed in the light of existing scientific evidence, with particular reference to that which points to the possible role of interactions between genes and environment. We conclude that mortality studies, particularly on migrant populations may be an important tool for clarifying this major issue.
Dementia and Geriatric Cognitive Disorders, 2011
tients prescribed antipsychotic drugs had a higher risk of death. This risk was highest for those... more tients prescribed antipsychotic drugs had a higher risk of death. This risk was highest for those prescribed conventional antipsychotics. At least part of the excess mortality may be due to the underlying neuropsychiatric symptoms that prompted the use of antipsychotics rather than a direct medication effect.
American Journal of Geriatric Psychiatry, Nov 1, 2010
Objectives: Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatme... more Objectives: Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Design: Cross-sectional, multicenter, clinical study. Participants: A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. Measurements: All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Results: Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N ϭ 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N ϭ 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. Conclusions: The authors' study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms.
Journal of the Neurological Sciences, Oct 1, 2009
problems 68 (56%) were identified as delayed language while 53 (44%) had aphasia. Out of 89 patie... more problems 68 (56%) were identified as delayed language while 53 (44%) had aphasia. Out of 89 patients with speech problems 15 (17%) patients had voice problems, 22 (24%) had articulation problems and 41 (47%) had fluency problems while only 11 (12%) patients had dysarthria. Conclusion: This study revealed that language problems are higher as compare to speech problems. In the domain of language problems delayed language problems are more common than aphasia. Moreover fluency problems are highest among all speech problems.
Alzheimer Disease & Associated Disorders, 2018
Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's... more Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's Diseases (AD/PD) and vice-versa. We evaluated whether a different distribution of known nongenetic risk factors for cancer and AD/PD, might explain their inverse relationship of occurrence. We nested 2 case-control studies in a subsample of a large cohort of 1,000,000 resident in Lombardy Region in Italy (n = 1515), followed-up for cancer and AD/PD occurrence since 1991 until 2012. Conditional logistic regression was performed to determine the odds ratios (OR) and 95% confidence intervals (CI) of AD/PD in subjects with and without cancer and the risk of cancer in those with and without AD/PD. A total of 54 incident cases of AD/PD and 347 cancer cases were matched with 216 and 667 controls, respectively. After controlling for low education, obesity, history of hypertension, diabetes, dyslipidemia, physical activity, smoking habit, alcohol consumption, and dietary habit, cancer was found inversely associated with the risk of AD/PD (OR, 0.66; 95% CI, 0.32-1.38), and the risk of cancer in AD/PD was similarly reduced (OR, 0.42; 95% CI, 0.20-0.91). Different exposures to nongenetic risk factors of both diseases do not explain their competitive relationship of occurrence.
Rivista di neurologia, 2002
Alzheimer disease and associated disorders, Jan 8, 2017
Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkins... more Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's Diseases (AD/PD) and vice-versa. We evaluated whether a different distribution of known nongenetic risk factors for cancer and AD/PD, might explain their inverse relationship of occurrence. We nested 2 case-control studies in a subsample of a large cohort of 1,000,000 resident in Lombardy Region in Italy (n=1515), followed-up for cancer and AD/PD occurrence since 1991 until 2012. Conditional logistic regression was performed to determine the odds ratios (OR) and 95% confidence intervals (CI) of AD/PD in subjects with and without cancer and the risk of cancer in those with and without AD/PD. A total of 54 incident cases of AD/PD and 347 cancer cases were matched with 216 and 667 controls, respectively. After controlling for low education, obesity, history of hypertension, diabetes, dyslipidemia, physical activity, smoking habit, alcohol consumption, and dietary habit, cancer was ...
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2010
Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both ... more Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Cross-sectional, multicenter, clinical study. A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxie...
Therapeutics and clinical risk management, 2007
Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressi... more Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and functional abilities associated with various behavioral disturbances. Its impact on public health and society as a whole is devastating. Slowing of the cognitive impairment, and improvements in disease duration, self-sufficiency and behavioral disturbances represent the best outcomes of pharmacologic therapy. Cholinesterase inhibitors (ChE-I) have been shown to be effective in treating the cognitive, behavioral, and functional deficits of AD. Rivastigmine is a dual inhibitor of both acetylcholine esterase (AChE) and butyrylcholinesterase (BuChE), enzymes involved in the hydrolysis of acetylcholine. Although this drug has been shown to be beneficial in patients with AD, its benefits are limited and their long-term effectiveness has not been well demonstrated.
Annali dell'Istituto superiore di sanità, 2005
The efficacy of medical interventions is their capacity of inducing positive modifications of the... more The efficacy of medical interventions is their capacity of inducing positive modifications of the natural history of diseases. The natural history of dementia is marked by specific events related to the cognitive and functional decline, but their occurrence is poorly predictable in individual patients being highly variable from patient to patient. For this reason it is difficult that the modest efficacy of available interventions for dementia, or their entity measured by clinical scales, may be perceived in clinical practice or in observational studies. Moreover in randomized clinical studies, the effect of this variability, in analogy to misclassification of exposition and/or disease in case control or cohort epidemiological studies, is that of an underestimation of the true efficacy of interventions.
Functional neurology
In this paper we review some theories about the process of senescence and death, in particular th... more In this paper we review some theories about the process of senescence and death, in particular the theory of accumulation of mutations and the theory of antagonistic pleiotropism. These theories are reviewed in the light of existing scientific evidence, with particular reference to that which points to the possible role of interactions between genes and environment. We conclude that mortality studies, particularly on migrant populations may be an important tool for clarifying this major issue.
Advances in Alzheimer's Disease, 2013
Objective: As the literature on conventional criteria for discriminating early-onset (EO) from la... more Objective: As the literature on conventional criteria for discriminating early-onset (EO) from late-onset (LO) Alzheimer's disease (AD) is sparse and controversial, the aim of this study was to establish a precise age at onset (AAO) criterion, by using a specific statistical procedure, and to describe the clinical characteristics of the two subgroups. Methods: Admixture analysis was performed to establish the AAO cutoff in a multi-center study including 2000 AD patients consecutively recruited in eight Italian Memory Clinics. None of the patients were taking acetylcholinesterase inhibitors, antipsychotic or anti-depressant drugs. At the first diagnostic visit, they were administered the Mini Mental State Examination, the Basic and Instrumental Activities of Daily Living and the Neuropsychiatric Inventory to assess clinical phenomenology. Results: Using a specific statistical procedure, we established that AAO that discriminated EOfrom LOAD was 66. Compared with the LOAD group, the EO-AD group showed longer duration of illness and a higher educational level as well as less severe functional impairment and delusions. Conclusions: Differences in sociodemographic and clinical characteristics, such as duration of illness, education and delusion severity, suggested the involvement of different pathogenic processes. Additional studies are needed to further investigate the mechanisms underlying the disorder in the two subgroups of AD patients.
Neurobiology of Aging, 2012
Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degenerati... more Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degeneration (FTLD) by haploinsufficiency mechanism, although their effects on brain tissue dysfunction and damage still remain to be clarified. In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the DMN. Our findings suggest that compensatory mechanisms of brain plasticity are present in GRN-related FTLD, but with different patterns at a preclinical and symptomatic disease stage.
Neuropsychologia, 2003
The breakdown of semantic knowledge relative to living and non-living categories was studied in p... more The breakdown of semantic knowledge relative to living and non-living categories was studied in patients with Alzheimer's disease (AD). The same living and non-living items were used in a semantic battery and in a semantic priming paradigm exploring automatic access to the semantic system. Although AD patients showed a semantic deficit on the intentional semantic battery, they demonstrated normal semantic facilitation on the priming task. In the AD group as a whole, the semantic impairment did not preferentially affect the living category either in the intentional or automatic condition. Instead, a prevalent deficit for the living category was found in three AD patients (14% of the group) on the intentional semantic tasks, but not on the automatic one. These findings support the view that the category effect may not be a generalised phenomenon in AD but may be restricted to a limited number of patients. The intentional/automatic dissociation of the semantic breakdown demonstrated by AD patients is discussed in relation to different theories regarding the organisation of semantic memory.
Riassunto. - L'efficacia degli interventi è definibile, in medicina, come la loro capacità d... more Riassunto. - L'efficacia degli interventi è definibile, in medicina, come la loro capacità di modificare positivamente la storia naturale delle malattie. La storia naturale delle demenze è contrassegnata da eventi conseguenti dal declino cognitivo e funzionale che caratterizza queste malattie. Questi eventi sono poco prevedibili nel singolo paziente dato che la loro occorrenza, o entità percepita attraverso le scale di misurazione, è largamente variabile da paziente a paziente. Ne consegue che l'efficacia dei trattamenti, modesta per quelli oggi disponibili, è difficilmente apprezzabile nella pratica clinica e persino negli studi osservazionali. Negli studi clinici randomizzati l'effetto di tale variabilità è infine analogo a quello della mis - classificazione in studi epidemiologici caso-controllo o di coorte e causa una sottostima dell'effettiva efficacia dei trattamenti. Parole chiave: demenza, scale cliniche, studi randomizzati e controllati. S u m m a ry ( V...
Neurology, 2013
Objective: To evaluate the incidence of cancer in persons with Alzheimer disease (AD) and the inc... more Objective: To evaluate the incidence of cancer in persons with Alzheimer disease (AD) and the incidence of AD dementia in persons with cancer. Methods: This was a cohort study in Northern Italy on more than 1 million residents. Cancer incidence was derived from the local health authority (ASL-Mi1) tumor registry and AD dementia incidence from registries of drug prescriptions, hospitalizations, and payment exemptions. Expected cases of AD dementia were calculated by applying the age-, sex-, and calendar year-specific incidence rates observed in the whole population to the subgroup constituted of persons with newly diagnosed cancers during the observation period (2004-2009). The same calculations were carried out for cancers in patients with AD dementia. Separate analyses were carried out for the time period preceding or following the index diagnosis for survivors and nonsurvivors until the end of 2009 and for different types and sites of cancer. Results: The risk of cancer in patients with AD dementia was halved, and the risk of AD dementia in patients with cancer was 35% reduced. This relationship was observed in almost all subgroup analyses, suggesting that some anticipated potential confounding factors did not significantly influence the results. Conclusions: The occurrence of both cancer and AD dementia increases exponentially with age, but with an inverse relationship; older persons with cancer have a reduced risk of AD dementia and vice versa. As AD dementia and cancer are negative hallmarks of aging and senescence, we suggest that AD dementia, cancer, and senescence could be manifestations of a unique phenomenon related to human aging. Neurology â 2013;81:322-328 GLOSSARY AD 5 Alzheimer disease; CI 5 confidence interval; ICD-10 5 International Classification of Diseases, 10th revision; RR 5 relative risk.
Neurobiology of Aging, 2000
Journal of the Neurological Sciences, 2009
problems 68 (56%) were identified as delayed language while 53 (44%) had aphasia. Out of 89 patie... more problems 68 (56%) were identified as delayed language while 53 (44%) had aphasia. Out of 89 patients with speech problems 15 (17%) patients had voice problems, 22 (24%) had articulation problems and 41 (47%) had fluency problems while only 11 (12%) patients had dysarthria. Conclusion: This study revealed that language problems are higher as compare to speech problems. In the domain of language problems delayed language problems are more common than aphasia. Moreover fluency problems are highest among all speech problems.