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Grazia D'Onofrio,
Daniele Sancarlo,
Francesco Panza,
Massimiliano Copetti,
Leandro Cascavilla,
Francesco Paris,
Davide Seripa,
Maria G Matera, Vincenzo Solfrizzi,
Fabio Pellegrini,
Alberto Pilotto
[show abstract]
[hide abstract]
ABSTRACT: Neuropsychiatric symptoms (NPS) are increasingly recognized as common in patients with dementia, both of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). In this study, 302 demented patients, 166 with AD and 136 with VaD, were evaluated for NPS according to the Neuropsychiatric Inventory (NPI) score at the Alzheimer's Evaluation Unit of Casa Sollievo della Sofferenza Hospital-IRCCS, San Giovanni Rotondo, Italy. A comprehensive geriatric assessment was also performed in all demented patients. The means of NPI scores did not differ in two groups. The overall prevalence of NPS was similar in both groups of patients (69.7% vs. 69.4%). Patients with AD had higher frequency in agitation/aggression and irritability/lability than VaD patients. Logistic analysis demonstrated a significant association between severity of the cognitive impairment and depression and eating disorders in both AD and VaD patients. The association with agitation/aggression, irritability/lability, and aberrant motor activity was found in AD only, and with apathy in VaD patients only. In both AD and VaD patients, there was a significant association between the impairment in activities of daily living (ADL) and the majority of NPI domains. A significant association was also found between the impairment of the instrumental activities of daily living (IADL) and agitation/aggression, anxiety, aberrant motor activity in AD and depression, apathy, irritability/lability, sleep disturbance and eating disorders in both AD and VaD patients. In particular, a causal mediation analysis was performed to better understand whether the relationship of NPS to functional impairment was direct or mediated by severity of cognitive dysfunction, i.e., Clinical dementia rating scale (CDR) score. Only agitation/aggression was mediated by the CDR score in affecting ADL status in VaD patients (OR: 1.12, 95% CI: 1.01-1.27). The NPI-Distress scores showed a significantly higher levels of distress in caregivers of AD than VaD. There were significant differences between AD and VaD patients with NPS, and these symptoms varied according to dementia subtype and severity and induced marked disability in ADL and IADL, increasing, prevalently, the distress of the caregivers of AD patients.
Current Alzheimer research 06/2012; 9(6):759-71. · 4.97 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Dementia is an increasingly common disease in the aging population, and the numbers are expected to rise exponentially in
coming years. Therefore, there is a critical need to potentially individualize new strategies able to prevent and to slow
down the progression of predementia and dementia syndromes. Despite a substantial increase in the epidemiological and clinical
evidence on frailty, there is no consensus on its definition or on what criteria should be used to identify older individuals
with frailty. Frailty appears to be a nonspecific state of vulnerability, which reflects multisystem physiological change.
In fact, current thinking is that not only physical but also psychological, cognitive and social factors contribute to this
multidimensional syndrome and need to be taken into account in its definition and treatment. Cognition has already been considered
as a component of frailty, and it has been demonstrated that it is associated with adverse health outcomes. In a recent population-based
study, physical frail demented patients were at higher risk of all-cause mortality over 3- and 7-year follow-up periods. Several
studies have also reported that physical frailty is associated with low cognitive performance, incidence of Alzheimer’s disease
(AD), and mild cognitive impairment, and AD pathology in older persons with and without dementia. Most frailty instruments
use a dichotomous scoring system classifying a person as either frail or not frail, while a continuous or an ordinal scoring
system on multiple levels would be preferable to be used as an outcome measure. Recently, a Multidimensional Prognostic Index
(MPI), derived from a standardized comprehensive geriatric assessment, was effective in predicting short- and long-term mortality
risk in hospitalized patients with dementia. Overall taken together these findings supported the concept that outcome measures
linked to multidimensional impairment may be extremely important in making clinical decisions, especially for monitoring drug
treatment in randomized clinical trials also for predementia and dementia syndromes.
Key wordsPhysical frailty–frailty indexes–all-cause mortality–dementia–Alzheimer’s disease–mild cognitive impairment–comprehensive geriatric assessment
The Journal of Nutrition Health and Aging 04/2012; 15(8):711-719. · 2.69 Impact Factor
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F. Panza,
C. Capurso,
A. D’Introno,
A. M. Colacicco,
V. Frisardi,
A. Santamato,
M. Ranieri,
P. Fiore,
G. Vendemiale,
D. Seripa,
A. Pilotto,
A. Capurso, V. Solfrizzi
[show abstract]
[hide abstract]
ABSTRACT: Since the therapeutic options currently available have demonstrated limited efficacy, the search for preventive strategies
for cognitive decline and dementia is mandatory. A possible role of vascular and lifestyle-related factors was recently proposed
for age-related changes of cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer’s disease,
AD) or vascular origin. At present, cumulative evidence suggested that vascular risk factors may be important in the development
of mild cognitive impairment (MCI), dementia, and AD. Among vascular-related factors, metabolic syndrome has been associated
with the risk of cognitive decline and overall dementia. Moderate alcohol drinking has been proposed as a protective factor
against MCI and dementia in several longitudinal studies, but contrasting findings also exist. However, in most cases, these
were only observational studies, and results are awaited from large multicenter randomized clinical trials in older persons.
At present, vascular risk factor management, lifestyle changes, and drugs could be employed together to delay the onset of
dementia syndromes.
The Journal of Nutrition Health and Aging 04/2012; 12(6):376-381. · 2.69 Impact Factor
-
V. Solfrizzi,
C. Capurs,
A. D’Introno,
A. M. Colacicco,
V. Frisardi,
A. Santamato,
M. Ranieri,
R. Fiore,
G. Vendemiale,
D. Seripa,
A. Pilotto,
A. Capurso,
F. Panza
[show abstract]
[hide abstract]
ABSTRACT: Currently available epidemiological evidence suggested that an increase of saturated fatty acids (SFA) could have negative
effects on cognitive functions, while increased polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA)
may be protective against cognitive decline. In a Southern Italian elderly population from the Italian Longitudinal Study
on Aging (ILSA), a clear reduction of risk of age-related cognitive decline (ARCD) has been found with elevated intake of
PUFA and MUFA. Furthermore, in the ILSA, while dietary fatty acids intakes were not associated with incident mild cognitive
impairment (MCI), high PUFA intake appeared to have borderline non-significant trend for a protective effect against the development
of MCI. These epidemiological findings on predementia syndromes, i.e. MCI or ARCD, together with a recent randomised controlled
trial on a possible effect on cognitive and depressive symptoms of ω-3 PUFA supplementation in patients with very mild AD,
suggested a possible role of fatty acids intake in maintaining adequate cognitive functioning and possibly in preventing or
delaying the onset of dementia.
The Journal of Nutrition Health and Aging 04/2012; 12(6):382-386. · 2.69 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Depression is recognized as being associated with increased mortality. However, there has been little previous research on the impact of longitudinal changes in late-life depressive symptoms on mortality, and of their remission in particular.Method
As part of a prospective, population-based study on a random sample of 5632 subjects aged 65-84 years, with a 10-year follow-up of vital status, depressive symptoms were assessed by the 30-item Italian version of the Geriatric Depression Scale (GDS). The number of participants in the GDS measurements was 3214 at baseline and 2070 at the second survey, 3 years later. Longitudinal changes in depressive symptoms (stable, remitted, worsened) were examined in participants in both evaluations (n=1941). Mortality hazard ratios (MHRs) according to severity of symptoms and their changes over time were obtained by means of Cox proportional hazards regression models, adjusting for age and other potentially confounding factors. RESULTS: Severity is significantly associated with excess mortality in both genders. Compared to the stability of depressive symptoms, a worsened condition shows a higher 7-year mortality risk [MHR 1.46, 95% confidence interval (CI) 1.15-1.84], whereas remission reduces by about 40% the risk of mortality in both genders (women MHR 0.55, 95% CI 0.32-0.95; men MHR 0.59, 95% CI 0.37-0.93). Neither sociodemographic nor medical confounders significantly modified these associations. CONCLUSIONS: Consistent with previous reports, the severity and persistence of depression are associated with higher mortality risks. Our findings extend the magnitude of the association demonstrating that remission of symptoms is related to a significant reduction in mortality, highlighting the need to enhance case-finding and successful treatment of late-life depression.
Psychological Medicine 04/2012; · 6.16 Impact Factor
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J. C. Lambert,
B. Grenier-Boley,
D. Harold,
D. Zelenika,
V. Chouraki,
Y. Kamatani,
K. Sleegers,
M. A. Ikram,
M. Hiltunen,
C. Reitz, [......],
D. Campion,
H. Soininen,
M. Breteler,
M. Riemenschneider,
C. Van Broeckhoven,
A. Alperovitch,
M. Lathrop,
D. A. Tregouet,
J. Williams,
P. Amouyel
[show abstract]
[hide abstract]
ABSTRACT: Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 x 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and Abeta plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Abeta42/Abeta40 ratio (best signal, P=5.4 x 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.Molecular Psychiatry advance online publication, 20 March 2012; doi:10.1038/mp.2012.14.
Molecular psychiatry 03/2012; · 15.05 Impact Factor
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B Grenier-Boley,
D Harold,
D Zelenika,
V Chouraki,
Y Kamatani,
K Sleegers,
M A Ikram,
M Hiltunen,
C Reitz,
I Mateo, [......],
M Riemenschneider,
C Van Broeckhoven,
A Alpérovitch,
M Lathrop,
D-A Trégouët,
J Williams,
P Amouyel 1] INSERM,
Lille,
France [2] Institut Pasteur de Lille,
France [3] Université Lille-Nord de France
Molecular psychiatry 03/2012; · 15.05 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Drugs currently used for the treatment of Alzheimer's disease (AD) produce limited clinical benefits, and there is no disease-modifying therapy yet available. Compounds that inhibit or modulate γ-secretase, the pivotal enzyme that generates β-amyloid (Aβ), are potential therapeutics for AD. This article briefly reviews the profile of γ-secretase inhibitors and modulators that have reached the clinic. Studies in both transgenic and non-transgenic animal models of AD have indicated that γ-secretase inhibitors, administered by the oral route, are able to lower brain Aβ concentrations. However, scanty data are available on the effects of these compounds on brain Aβ deposition after prolonged administration. γ-Secretase inhibitors may cause abnormalities in the gastrointestinal tract, thymus, spleen, skin, and decrease in lymphocytes and alterations in hair color in experimental animals and in man, effects believed to be associated with the inhibition of the cleavage of Notch, a transmembrane receptor involved in regulating cell-fate decisions. Unfortunately, two large Phase III clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of the observation of a detrimental cognitive and functional effect of the drug. These detrimental effects were mainly ascribed to the inhibition of the processing of an unknown substrate of γ-secretase. It has been also hypothesized that the detrimental cognitive effects observed after semagacestat administration are due to the accumulation of the neurotoxic precursor of Aβ (the carboxy-terminal fragment of amyloid precursor protein, APP, or CTFβ) resulting from the block of the γ-secretase cleavage activity on APP. Some non-steroidal anti-inflammatory drugs and other small organic molecules have been found to modulate γ-secretase shifting its cleavage activity from longer to shorter Aβ species without affecting Notch cleavage. However, two large Phase III studies in mild AD patients with tarenflurbil, a putative γ-secretase modulator, were also completely negative. The failure of tarenflurbil was ascribed to low potency and brain penetration. New more selective γ-secretase inhibitors and more potent, more brain penetrant γ-secretase modulators are being developed with the hope of overcoming the previous setbacks. Further understanding of the reasons of the failures of these γ-secretase-based drugs in AD may be important for the future research on effective treatments for this devastating disease.
Current Medicinal Chemistry 11/2011; 18(35):5430-47. · 4.86 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Dementia is an increasingly common disease in the aging population, and the numbers are expected to rise exponentially in coming years. Therefore, there is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Despite a substantial increase in the epidemiological and clinical evidence on frailty, there is no consensus on its definition or on what criteria should be used to identify older individuals with frailty. Frailty appears to be a nonspecific state of vulnerability, which reflects multisystem physiological change. In fact, current thinking is that not only physical but also psychological, cognitive and social factors contribute to this multidimensional syndrome and need to be taken into account in its definition and treatment. Cognition has already been considered as a component of frailty, and it has been demonstrated that it is associated with adverse health outcomes. In a recent population-based study, physical frail demented patients were at higher risk of all-cause mortality over 3- and 7-year follow-up periods. Several studies have also reported that physical frailty is associated with low cognitive performance, incidence of Alzheimer's disease (AD), and mild cognitive impairment, and AD pathology in older persons with and without dementia. Most frailty instruments use a dichotomous scoring system classifying a person as either frail or not frail, while a continuous or an ordinal scoring system on multiple levels would be preferable to be used as an outcome measure. Recently, a Multidimensional Prognostic Index (MPI), derived from a standardized comprehensive geriatric assessment, was effective in predicting short- and long-term mortality risk in hospitalized patients with dementia. Overall taken together these findings supported the concept that outcome measures linked to multidimensional impairment may be extremely important in making clinical decisions, especially for monitoring drug treatment in randomized clinical trials also for predementia and dementia syndromes.
The Journal of Nutrition Health and Aging 08/2011; 15(8):711-9. · 2.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: At present, the search for preventive strategies for cognitive decline and dementia appears to be of crucial importance, given that the therapeutic options currently available have demonstrated limited efficacy. Cumulative epidemiological evidence suggested that vascular and vascular-related factors may be important for the development of agerelated cognitive decline (ARCD), mild cognitive impairment (MCI), and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). Among vascular-related factors, metabolic syndrome (MetS) has been associated with the increased risk of predementia syndromes (ARCD and MCI), overall dementia, and VaD, but contrasting findings also exist on the possible role of MetS in AD. In the next future, trials could then be undertaken to determine if modifications of these risks including inflammation, another factor probably related to MetS, could lower risk of developing cognitive decline. If MetS is associated with increased risk of developing cognitive impairment, then early identification and treatment of these individuals at risk might offer new avenues for disease course modification. Future research aimed at identifying mechanisms that underlie comorbid associations will not only provide important insights into the causes and interdependencies of predementia and dementia syndromes, but will also inspire novel strategies for treating and preventing these disorders. At present, vascular risk factor management could be decisive in delaying the onset of dementia syndromes or in preventing the progression of predementia syndromes.
Current Alzheimer Research 07/2011; 8(5):492-509. · 3.95 Impact Factor
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V. Solfrizzi,
V. Frisardi,
D. Seripa,
G. Logroscino,
B. P. Imbimbo,
G. D'Onofrio,
F. Addante,
D. Sancarlo,
L. Cascavilla,
A. Pilotto,
F. Panza
[show abstract]
[hide abstract]
ABSTRACT: There is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Only recently higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline although the Mediterranean diet (MeDi) combines several foods, micro- and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggested a possible association among fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA) (particularly, n-3 PUFA) and reduced risk of cognitive decline and dementia. Light to moderate alcohol use may be associated with a reduced risk of incident dementia and Alzheimer's disease (AD), while for vascular dementia, cognitive decline, and predementia syndromes the current evidence is only suggestive of a protective effect. Finally, the limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supported a protective role of these macronutrients against cognitive decline, dementia, and AD. Moreover, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD, and decreased all-causes mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk for AD, but also for predementia syndromes and their progression to overt dementia. Nonetheless, at present, no definitive dietary recommendations are possible. However, high levels of consumption of fats from fish, vegetable oils, non-starchy vegetables, low glycemic fruits, and diet low in foods with added sugars and with moderate wine intake should be encouraged. In fact, this dietary advice is in accordance with recommendations for lowering the risk of cardiovascular disease, obesity, diabetes, and hypertension and might open new ways for the prevention and management of cognitive decline and dementia.
Current Alzheimer Research 07/2011; 8(5):520-542. · 3.95 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Low back pain (LBP) is a common musculoskeletal disorder that is highly prevalent in the general population. Management of this pathology includes numerous interventions depending on pain severity: analgesic, nonsteroidal anti-inflammatory drugs, steroid injections. However, the effect size and duration of symptom relief are limited. Physical therapy (ultrasound [US], laser therapy, manual therapy, interferential current therapy, Back School, aerobic work, therapeutic aquatic exercise acupuncture) have been reported often with mixed results.
To evaluate the short-term effectiveness of high-intensity laser therapy (HILT) versus ultrasound (US) therapy in the treatment of LBP.
Randomized clinical trial.
University hospital.
Thirty patients with LBP were randomly assigned to a HILT group or a US therapy group.
Study participants received fifteen treatment sessions of HILT or US therapy over a period of three consecutive weeks (five days/week).
For the 30 study participants there were no between-group differences at baseline in Visual Analogic Scale (VAS) and Oswestry Low Back Pain Disability Questionnaire (OLBPDQ) scores. At the end of the 3-week intervention, participants in the HILT group showed a significantly greater decrease in pain (measured by the VAS) and an improvement of related disability (measured by the OLBPDQ) compared with the group treated with US therapy.
Our findings obtained after 15 treatment sessions with the experimental protocol suggested greater effectiveness of HILT than of US therapy in the treatment of LBP, proposing HILT as a promising new therapeutic option into the rehabilitation of LBP.
European journal of physical and rehabilitation medicine 06/2011; 47(3):367-73. · 1.40 Impact Factor
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V Solfrizzi,
V Frisardi,
D Seripa,
G Logroscino,
B P Imbimbo,
G D'Onofrio,
F Addante,
D Sancarlo,
L Cascavilla,
A Pilotto,
F Panza
[show abstract]
[hide abstract]
ABSTRACT: There is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Only recently higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline although the Mediterranean diet (MeDi) combines several foods, micro- and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggested a possible association among fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA) (particularly, n-3 PUFA) and reduced risk of cognitive decline and dementia. Light to moderate alcohol use may be associated with a reduced risk of incident dementia and Alzheimer's disease (AD), while for vascular dementia, cognitive decline, and predementia syndromes the current evidence is only suggestive of a protective effect. Finally, the limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supported a protective role of these macronutrients against cognitive decline, dementia, and AD. Moreover, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD, and decreased all-causes mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk for AD, but also for predementia syndromes and their progression to overt dementia. Nonetheless, at present, no definitive dietary recommendations are possible. However, high levels of consumption of fats from fish, vegetable oils, non-starchy vegetables, low glycemic fruits, and diet low in foods with added sugars and with moderate wine intake should be encouraged. In fact, this dietary advice is in accordance with recommendations for lowering the risk of cardiovascular disease, obesity, diabetes, and hypertension and might open new ways for the prevention and management of cognitive decline and dementia.
Current Alzheimer research 05/2011; 8(5):520-42. · 4.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: At present, the search for preventive strategies for cognitive decline and dementia appears to be of crucial importance, given that the therapeutic options currently available have demonstrated limited efficacy. Cumulative epidemiological evidence suggested that vascular and vascular-related factors may be important for the development of age-related cognitive decline (ARCD), mild cognitive impairment (MCI), and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). Among vascular-related factors, metabolic syndrome (MetS) has been associated with the reduced risk of predementia syndromes (ARCD and MCI), overall dementia, and VaD, but contrasting findings also exist on the possible role of MetS in AD. In the next future, trials could then be undertaken to determine if modifications of these risks including inflammation, another factor probably related to MetS, could lower risk of developing cognitive decline. If MetS is associated with increased risk of developing cognitive impairment, then early identification and treatment of these individuals at risk might offer new avenues for disease course modification. Future research aimed at identifying mechanisms that underlie comorbid associations will not only provide important insights into the causes and interdependencies of predementia and dementia syndromes, but will also inspire novel strategies for treating and preventing these disorders. At present, vascular risk factor management could be decisive in delaying the onset of dementia syndromes or in preventing the progression of predementia syndromes.
Current Alzheimer research 05/2011; 8(5):492-509. · 4.97 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Recent advances in our understanding of the neurobiology of Alzheimer's disease (AD) have led to the development of putative disease-modifying treatments. The most revolutionary of these approaches consists in the removal of brain β-amyloid (Aβ) via anti-Aβ antibodies. Brain imaging and neuropathological studies have shown the ability of both active and passive anti-Aβ immunotherapies of clearing Aβ deposits from the brain of the AD patients. An active anti-Aβ vaccine preparation, AN1792, has been used in AD patients with some clues of clinical efficacy but causing meningoencephalitis in about 6% of patients and it has been abandoned. Several second-generation active Aβ vaccines and passive Aβ immunotherapies have been developed and are under clinical investigation with the aim of accelerating Aβ clearance from the brain of the AD patients. The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce Aβ burden in the brain of AD patients. However, the preliminary cognitive efficacy of bapineuzumab appears uncertain. The occurrence of vasogenic edema, especially in apolipoprotein E 4 carriers, may limit its clinical use and have led to abandon the highest dose of the drug (2 mg/kg). The results of four ongoing large Phase III trials on bapineuzumab will tell us if passive anti-Aβ immunization is able to alter the course if this devastating disease.
Current Alzheimer research 05/2011; 8(8):808-17. · 4.97 Impact Factor
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E Genin,
D Hannequin,
D Wallon,
K Sleegers,
M Hiltunen,
O Combarros,
M J Bullido,
S Engelborghs,
P De Deyn,
C Berr, [......],
D Seripa,
D Galimberti,
F Licastro,
H Soininen,
J-F Dartigues,
M I Kamboh,
C Van Broeckhoven,
J C Lambert,
P Amouyel,
D Campion
[show abstract]
[hide abstract]
ABSTRACT: Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.
Molecular psychiatry 05/2011; 16(9):903-7. · 15.05 Impact Factor
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V Frisardi, V Solfrizzi,
P B Imbimbo,
C Capurso,
A D'Introno,
A M Colacicco,
G Vendemiale,
D Seripa,
A Pilotto,
A Capurso,
F Panza
[show abstract]
[hide abstract]
ABSTRACT: Pathological, genetic, biochemical and pharmacological studies support the hypothesis that brain accumulation of oligomeric species of beta-amyloid (Abeta) peptides may cause Alzheimer's disease (AD). Drugs currently used for the treatment of AD produce limited clinical benefits and do not treat the underlying causes of the disease. In the last 10 years, new therapeutic approaches targeting Abeta have been discovered and developed with the hope of modifying the natural history of the disease. Several active and passive immunotherapy approaches are under investigation in clinical trials with the aim of accelerating Abeta clearance from the brain of the AD patients. The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Abeta monoclonal antibodies, that is being tested in two large late-stage trials. Compounds that interfere with proteases regulating Abeta formation from amyloid precursor protein (APP) are also actively pursued. Unfortunately, the most biologically attractive of these proteases, beta-secretase, that regulates the first step of the amyloidogenic APP metabolism, was found to be particularly problematic to block and only one compound (CTS21166) has reached clinical testing so far. Conversely, several inhibitors of gamma-secretase, the protease that regulates the last metabolic step generating Abeta, have been identified, the most advanced being LY-450139 (semagacestat), presently in Phase III clinical development. Compounds that stimulate alpha-secretase, the enzyme responsible for the non-amyloidogenic metabolism of APP, are also being developed one of them, EHT-0202, has recently started a Phase II study. Furthermore, brain penetrant inhibitors of Abeta aggregation have been identified and one of such compounds, PBT-2, has produced encouraging neuropsychological results in a recently completed Phase II study. With all these anti-Abeta approaches in clinical testing, we will know in few years if the Abeta hypothesis of AD is correct.
Current Alzheimer research 11/2009; 7(1):40-55. · 4.97 Impact Factor
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V Solfrizzi,
C Capurso,
A D'Introno,
A M Colacicco,
V Frisardi,
A Santamato,
M Ranieri,
P Fiore,
G Vendemiale,
D Seripa,
A Pilotto,
A Capurso,
F Panza
[show abstract]
[hide abstract]
ABSTRACT: Currently available epidemiological evidence suggested that an increase of saturated fatty acids (SFA) could have negative effects on cognitive functions, while increased polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) may be protective against cognitive decline. In a Southern Italian elderly population from the Italian Longitudinal Study on Aging (ILSA), a clear reduction of risk of age-related cognitive decline (ARCD) has been found with elevated intake of PUFA and MUFA. Furthermore, in the ILSA, while dietary fatty acids intakes were not associated with incident mild cognitive impairment (MCI), high PUFA intake appeared to have borderline non-significant trend for a protective effect against the development of MCI. These epidemiological findings on predementia syndromes, i.e. MCI or ARCD, together with a recent randomised controlled trial on a possible effect on cognitive and depressive symptoms of omega-3 PUFA supplementation in patients with very mild AD, suggested a possible role of fatty acids intake in maintaining adequate cognitive functioning and possibly in preventing or delaying the onset of dementia.
The Journal of Nutrition Health and Aging 07/2008; 12(6):382-6. · 2.69 Impact Factor
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F Panza,
C Capurso,
A D'Introno,
A M Colacicco,
V Frisardi,
A Santamato,
M Ranieri,
P Fiore,
G Vendemiale,
D Seripa,
A Pilotto,
A Capurso, V Solfrizzi
[show abstract]
[hide abstract]
ABSTRACT: Since the therapeutic options currently available have demonstrated limited efficacy, the search for preventive strategies for cognitive decline and dementia is mandatory. A possible role of vascular and lifestyle-related factors was recently proposed for age-related changes of cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin. At present, cumulative evidence suggested that vascular risk factors may be important in the development of mild cognitive impairment (MCI), dementia, and AD. Among vascular-related factors, metabolic syndrome has been associated with the risk of cognitive decline and overall dementia. Moderate alcohol drinking has been proposed as a protective factor against MCI and dementia in several longitudinal studies, but contrasting findings also exist. However, in most cases, these were only observational studies, and results are awaited from large multicenter randomized clinical trials in older persons. At present, vascular risk factor management, lifestyle changes, and drugs could be employed together to delay the onset of dementia syndromes.
The Journal of Nutrition Health and Aging 07/2008; 12(6):376-81. · 2.69 Impact Factor
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Neurology 01/2008; 69(23):2186; author reply 2186-7. · 8.31 Impact Factor
