Cardiac sources of cerebral embolism in people with migraine.

BACKGROUND AND PURPOSE: Whether the reported association between migraine with aura (MA) and cardioembolic stroke may be explained by a higher rate of atrial fibrillation (AF) or by other potential cardiac sources of cerebral embolism remains to be determined. METHODS: In the setting of a single centre cohort study of consecutive patients with acute brain ischaemia stratified by migraine status, the association between AF as well as patent foramen ovale (PFO) and migraine was explored. RESULTS: In all, 1738 patients (1017 [58.5%] men, mean age 67.9 ± 14.9 years) qualified for the analysis. Aging was inversely associated with migraine, whilst women had a >3-fold increased disease risk (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.58-5.66). No association between AF and history of migraine or its pathogenic subtypes was detected. Conversely, migraine was associated with PFO, both in the entire cohort (OR 1.84, 95% CI 1.07-3.16) and in patients aged ≤55 years (OR 2.21, 95% CI 1.16-4.22). This association was significant for MA (OR 2.92, 95% CI 1.32-6.45 in the entire cohort; OR 2.92, 95% CI 1.15-7.41 in patients aged ≤55 years) and in women (OR 8.23, 95% CI 2.06-32.77), but not for migraine without aura. CONCLUSIONS: In patients with brain ischaemia migraine is not associated with AF. Conversely, there is a probable relation between migraine, especially MA, and PFO in patients who are younger and have a more favourable vascular risk factor profile, and in women.

Visuospatial learning is fostered in migraine: evidence by a neuropsychological study.

BACKGROUND: Cognitive profile in migraine patients still remains undefined. Contradictory evidence has been provided, with impairments in different cognitive domains, normal cognition, or even better performance compared to healthy controls (HC). The latter is of particular interest considering the evidence of glutamatergic upregulation in migraine, particularly in the visual cortex, and the role of the glutamatergic system in synaptic plasticity and learning. The aim of our study is to compare cognitive performance for visuospatial memory and learning (supraspan modality) between migraineurs without aura (MwoA) and HC. METHODS: Twenty-one subjects suffering from MwoA and 21 HC were enrolled. Migraineurs during the interictal phase and HC underwent visuospatial memory test (Corsi test) and verbal memory test (Buschke Selective Reminding Test) in supraspan modality, Trial Making Test A (TMTA) and B (TMTB) as test exploring attention, and TMTB-TMTA as test of executive functioning. Depression was assessed with the Beck Depression Inventory Short Form (BDI-SF). Migraine characteristics (i.e., disease duration and frequency expressed as attacks per month) were collected. RESULTS: Subjects with MwoA showed better performance than HC in test exploring both short (p = 0.002) and long-term (p = 0.001) visuospatial memory. No significant difference between groups was found in verbal memory, attention, executive functioning, and depression (BDI-SF). No significant association emerged between cognitive performance and migraine characteristics. DISCUSSION: Subjects with MwoA had significant better performance in visuospatial memory and learning than HC. Occipito-parietal hyperexcitability (in particular in the visual cortex), which is a hallmark of the migraine brain, would probably explain these results. These data need to be confirmed in larger samples of migraineurs.

The Italian dementia with Lewy bodies study group (DLB-SINdem): toward a standardization of clinical procedures and multicenter cohort studies design.

Dementia with Lewy bodies (DLB) causes elevated outlays for the National Health Systems due to high institutionalization rate and patients' reduced quality of life and high mortality. Furthermore, DLB is often misdiagnosed as Alzheimer's disease. These data motivate harmonized multicenter longitudinal cohort studies to improve clinical management and therapy monitoring. The Italian DLB study group of the Italian Neurological Society for dementia (SINdem) developed and emailed a semi-structured questionnaire to 572 national dementia centers (from primary to tertiary) to prepare an Italian large longitudinal cohort. The questionnaire surveyed: (1) prevalence and incidence of DLB; (2) clinical assessment; (3) relevance and availability of diagnostic tools; (4) pharmacological management of cognitive, motor, and behavioural disturbances; (5) causes of hospitalization, with specific focus on delirium and its treatment. Overall, 135 centers (23.6 %) contributed to the survey. Overall, 5624 patients with DLB are currently followed by the 135 centers in a year (2042 of them are new patients). The percentage of DLB patients was lower (27 ± 8 %) than that of Alzheimer's disease and frontotemporal dementia (56 ± 27 %) patients. The majority of the centers (91 %) considered the clinical and neuropsychological assessments as the most relevant procedure for a DLB diagnosis. Nonetheless, most of the centers has availability of magnetic resonance imaging (MRI; 95 %), electroencephalography (EEG; 93 %), and FP-CIT single photon emission-computerized tomography (SPECT; 75 %) scan for clinical applications. It will be, therefore, possible to recruit a large harmonized Italian cohort of DLB patients for future cross-sectional and longitudinal multicenter studies.

The symptom of low mood in the prodromal stage of mild cognitive impairment and dementia: a cohort study of a community dwelling elderly population.

OBJECTIVE: To investigate the symptom of low mood as a predictor of mild cognitive impairment (MCI) and its progression to dementia, taking into account: (i) MCI severity, (ii) time of assessment and (iii) interaction with other factors. METHODS: 764 cognitively healthy elderly subjects living in the community, from the Kungsholmen Project. Participants were assessed by direct interview to detect low mood. Subjects were then followed for 6 years to identify those who developed MCI. People with incident MCI were followed for a further 3 years to assess progression to dementia. RESULTS: People with low mood at baseline had a 2.7-fold (95% CI 1.9 to 3.7) increased risk of developing MCI at follow-up. The association was stronger for amnestic MCI (aMCI: HR 5.8; 95% CI 3.1 to 10.9) compared with global cognitive impairment (other cognitive impairment no dementia, oCIND: HR 2.2; 95% CI 1.5 to 3.3). ApoE-ε4 interacted with low mood in a synergistic fashion, increasing the risk of aMCI, while no interaction with psychiatric, vascular, frailty related or psychosocial factors was observed. Low mood at baseline, as opposed to low mood co-occurring with MCI, was associated with a 5.3-fold (95% CI 1.2 to 23.3) increased risk of progression to dementia in aMCI. In contrast, no association was found in oCIND. CONCLUSION: Low mood was more strongly associated with aMCI than with global cognitive impairment. Progression towards dementia was predicted only by low mood manifest in the prodromal stage of MCI. These findings indicate that low mood is particularly prominent in the very early stages of cognitive decline.

Validation study of the Italian Addenbrooke's Cognitive Examination Revised in a young-old and old-old population.

AIMS: The main aims of the study were the translation and the subsequent validation in Italian of the Addenbrooke's Cognitive Examination Revised (ACE-R), and the evaluation of its usefulness in discriminating cognitively normal subjects from patients with mild dementia in an elderly population. METHODS: The ACE-R was translated and adapted into Italian. The Italian ACE-R was administered to a group of 179 elderly subjects (72 cognitively healthy and 107 subjects with mild dementia, mean age 75.4±6.4 years). The group was stratified into two subsamples according to age, i.e. a young-old (<75 years) and an old-old (≥75 years) group, in order to evaluate the sensitivity and specificity of the test in detecting dementia in different age strata of elderly subjects. RESULTS: The reliability of the Italian ACE-R was extremely good (α-coefficient=0.85). Two different cutoffs were identified for young-old (cutoff 79; sensitivity 90% and specificity 80%) and old-old subjects (cutoff 60; sensitivity 82% and specificity 100%). CONCLUSIONS: The Italian ACE-R is a valid screening tool to detect dementia, especially in the old-old population, which represents not only the fastest growing age group but also the group at the highest risk of dementia in Western countries.

Cognitive performance in elderly patients undergoing carotid endarterectomy or carotid artery stenting: a twelve-month follow-up study.

BACKGROUND: It is still a matter of debate if and to what extent carotid endarterectomy (CEA) and carotid artery stenting (CAS) impair cognitive functioning in the elderly. METHODS: We conducted a nonrandomized clinical trial on subjects with asymptomatic carotid artery stenosis comparing CEA (n = 28; 24 males and 4 females; 72.6 +/- 5.8 years old) with CAS (n = 29; 17 males and 12 females; 75.1 +/- 5.7 years old). Cognition, mood and functional status were evaluated by a broad spectrum of tests performed on the day prior to carotid reopening as well as 3 and 12 months after. RESULTS: No significant differences in scores on cognitive tests including the Babcock story recall test and Rey's auditory verbal learning test (memory), category naming test (verbal fluency), trail-making test parts A and B (attention and executive function) and controlled oral word association test (executive functioning) were observed 3 and 12 months after carotid reopening independent of the technique used. Only scores on the copy drawing test (visuospatial and constructional abilities) slightly but significantly (p < 0.05) worsened in the CAS group 12 months after the intervention. No significant differences between the CEA and CAS groups were detected regarding mood and functional status after 3 and 12 months. CONCLUSIONS: CEA and CAS seem to be safe procedures in elderly patients in terms of cognitive, mood and functional status in the short and long term. CAS might be preferred for the shorter hospital stay, but further studies with a larger number of old and oldest old subjects with a longer follow-up are needed to better understand the cost-effectiveness of both treatments.

Neuropsychiatric symptoms in 921 elderly subjects with dementia: a comparison between vascular and neurodegenerative types.

OBJECTIVE: i) to describe the neuropsychiatric profile of elderly subjects with dementia by comparing vascular (VaD) and degenerative dementias, i.e. dementia with Lewy bodies (DLB) and Alzheimer's disease (AD); ii) to assess whether the severity and type of dementia are associated with clinically relevant neuropsychiatric symptoms (CR-NPS). METHOD: One hundred and thirty-one out-patients with VaD, 100 with DLB and 690 with AD were studied. NPS were evaluated by the neuropsychiatric inventory (NPI). RESULTS: Vascular dementia had lower total and domain-specific NPI scores and a lower frequency of CR-NPS than AD and DLB, for which frequency of CR-NPS increased significantly with disease severity, particularly in AD. Logistic regression analysis showed that a higher CDR score and a diagnosis of degenerative dementia were independently associated with CR-NPS. CONCLUSION: Vascular dementia is associated less with CR-NPS than AD and DLB. Frequency of CR-NPS increases with disease severity in AD and, to a lesser extent, in DLB.

Vascular risk factors in mild cognitive impairment subtypes. Findings from the ReGAl project.

BACKGROUND AND AIM: To investigate the role of vascular risk factors in different subtypes of mild cognitive impairment (MCI) in a multicentric, clinic-based, cross-sectional study. METHODS: Two-hundred and seven subjects with MCI were included in the study: 33 with single non-memory MCI (snmMCI), 42 with multiple-domain amnestic MCI (mdMCI-a) and 132 with amnestic MCI (aMCI). Several clinical vascular risk factors and magnetic resonance imaging (MRI) brain lesions were evaluated. RESULTS: snmMCI showed a higher frequency of ischaemic heart disease and of transient ischaemic attack (TIA)/stroke, a higher Hachinski ischaemic score and a higher frequency of white-matter lesions on MRI compared to aMCI. Subjects with mdMCI-a showed clinical characteristics similar to aMCI, except for a higher frequency of a history of TIA/stroke. CONCLUSION: Our findings suggest that snmMCI may be considered a vascular cognitive disorder.

Effects of levodopa oral bolus on the kinematics of the pointing movements in Parkinson's disease patients.

We studied the time-course of a levodopa oral bolus effects on the kinematics of patients affected by a mild akinetic-rigid form of idiopathic Parkinson's disease (PD). Eleven PD patients were evaluated: a) in OFF-state, that is before their first medication or after its withdrawal, b) in ON-state, that is at 1/2, 1, 2, 3, 4, 5, 6, 24, 30 and 48 hours after the administration of 250 mg of levodopa plus 25mg of carbidopa. The main kinematics (i. e.movement time, peak of velocity, peak of acceleration and peak of deceleration) of pointing movements to six target-stimuli placed on the horizontal plane of a table were recorded. Clinical conditions were assessed according to the Motor Examination section of the Unified Parkinson's Disease Rating Scale. The levopoda bolus had stable clinical effects only within the first six hours from its administration. The decline of the clinical response was marked by the changes of peak acceleration whereas other kinematics (i. e. movement time and the peak of velocity) changed also in the late observations (24, 30 and 48 hours after drug intake). The dissociation between the persistent improvement on movement time on peak velocity and the rapid deterioration of levodopa effects on early kinematics (i. e. peak acceleration) could be accounted for by a progressive decline in movement programming.

Amyloid precursor protein in platelets of patients with Alzheimer disease: effect of acetylcholinesterase inhibitor treatment.

BACKGROUND: Amyloid precursor protein (APP) forms with apparent molecular weights of 130, 110, and 106 kd are present in human platelets. It has been demonstrated that Alzheimer disease (AD) is specifically associated with a decreased APP forms ratio in platelets. OBJECTIVE: To investigate whether acetylcholinesterase (AChE) inhibitor treatment modifies the ratio of platelet APP forms in patients with AD. PATIENTS AND METHODS: From a large sample of patients with probable AD, 30 with mild to moderate AD were selected. Each patient underwent a clinical evaluation including the Mini-Mental State Examination (MMSE) and platelet APP forms analysis at baseline and after 30 days. During this interval, 20 of 30 patients with AD were treated with donepezil hydrochloride (5 mg/d), a piperidine phosphate-based cholinesterase inhibitor. Platelets were subjected to Western blot analysis using monoclonal antibody (22C11). The ratio between the immunoreactivity of the higher-molecular-weight APP form (130 kd) and the lower forms (106 and 110 kd) was measured. RESULTS: All patients taking donepezil completed the 30 days of treatment without adverse effects. The platelet APP forms ratio at baseline did not differ between the 2 AD groups (mean +/- SD optical density ratio: untreated AD, 0.47 +/- 0.12; treated AD, 0.38 +/- 0.18), whereas a significant difference was found at follow-up (mean +/- SD optical density ratio: untreated AD, 0.45 +/- 0.17; treated AD, 0.77 +/- 0.29; P<.001). A significant improvement in MMSE scores in treated AD patients was observed from baseline (16.9 +/- 3.8) to 30 days (18.9 +/- 4.42) (P<.009, 30 days vs baseline), but no significant correlation was found in treated AD patients between MMSE score improvement and APP forms/ratio increase (P =.09). CONCLUSIONS: Administration of AChE inhibitors increases the ratio of APP forms in platelets of patients with AD, suggesting a potential effect of AChE inhibitors on APP trafficking or processing in a peripheral cell.

Amyloid precursor protein in platelets: a peripheral marker for the diagnosis of sporadic AD.

BACKGROUND: An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD. OBJECTIVE: To evaluate the sensitivity and the specificity of platelet APP forms' ratio (APPr) as a marker for AD. METHODS: Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands. RESULTS: Mean APPr levels were decreased in AD patients (mean OD +/- SD = 0.35 +/- 0.18) compared with the CON group (mean OD +/- SD = 0.92 +/- 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05). CONCLUSION: Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.

Effects of 8-OH-DPAT on open field performance of young and aged rats prenatally exposed to diazepam: a tool to reveal 5-HT1A receptor function.

Central GABAergic and serotoninergic systems interact with one another and are implicated in controlling different behaviours. A gentle early long-lasting handling can prevent the deficits in locomotion and exploration in open field (O.F.) in 3-month-old male rats prenatally exposed to diazepam (DZ). Purpose of this study was to extend the research to older handled rats prenatally exposed to DZ and to assess the activity of 5-HT1A receptors (Rs), evaluating the performance in O.F. at 3 and 18 months of age following 8-OH-DPAT administration. A single daily s.c. injection of DZ (1.5 mg/kg) from gestation day 14 to gestation day 20 induced in aged, but not in young rats, a decrease in total distance travelled (TDT) and in rearing frequency (RF) and an increase of transitions from the periphery to the centre of the arena (CNT) and in the time spent in the centre of the arena (CAT), compared to controls. 8-OH-DPAT (0.150 mg/kg s.c.), given 1 h before testing, increased TDT and decreased RF, CNT and CAT in both vehicle- and DZ-exposed young rats. In aged rats prenatally exposed to DZ, 8-OH-DPAT induced an increase in TDT and a slight decrease in RF, CNT and CAT. These findings indicate that the effects of handling and of 8-OH-DPAT in prenatally DZ-exposed rats are age-dependent and suggest that O.F. test can represent a valid tool to identify the changes in 5-HT1A Rs activity following drug treatment.

Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations.

The prevalence and pattern of cognitive impairment in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (nSLE) overt neuropsychiatric manifestations were investigated. Fifty-two nSLE patients, 23 NPSLE patients and 27 healthy controls were evaluated with a battery of standardized neuropsychological and psychological tests. Disease duration, disease activity index, and current corticosteroid therapy were collected. Cognitive impairment was identified in 14 (26.9%) and in 12 (52.2%) of subjects with nSLE and NPSLE, respectively. Both SLE groups showed a significant impairment compared with controls on tasks assessing verbal and non-verbal long-term memory, and visuoconstructional abilities. In addition, NPSLE patients reported worse performances than both nSLE patients and controls on task evaluating short-term visuospatial memory. NPSLE subjects were significantly more anxious and depressed compared to both nSLE subjects and controls. By multivariate analysis, only depression levels, among clinical variables, significantly predicted cognitive performance. This study shows that cognitive impairment occurs frequently in both nSLE and NPSLE subjects. The higher frequency in NPSLE may be related to coexisting depressive disturbances.

The C(-260)>T gene polymorphism in the promoter of the CD14 monocyte receptor gene is not associated with acute myocardial infarction.

CD surface molecules mediates cell activation and signaling. In particular, CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide. Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis. It has been recently shown that a C(-260)T polymorphism in the promoter of the CD14 receptor may be a risk factor for coronary artery disease. Recently this association has been questioned because no increased risk was found with the T allele, even in the homozygous state. In the present study we investigated a possible association between the C(-260)T polymorphism in the CD14 promoter and acute myocardial infarction. Two hundred and thrteen patients with and acute myocardial infarction 213 healthy controls were included in the study. Genotype frequencies of the C(-260)T polymorphism in the CD14 promoter were determined by polimerase chain reaction and the amplified product was cleaved with HaeIII. The frequency of the T allele was not significantly different in patients compared with controls. In this study we were not able to detect differences of frequency of the allele T (-260) in the promoter of the CD14 receptor gene in survivors of myocardial infarction and controls.

Occurrence of cognitive impairment and dementia in the community: a 9-year-long prospective study.

OBJECTIVE: To determine incidence rates of non-dementia cognitive impairment, to examine the impact of attrition due to death on the observed incidence estimates, and to compare the observed and corrected estimates of non-dementia cognitive impairment with dementia incidence rates. METHODS: A total of 1,435 persons without dementia aged 75+ from the Kungsholmen Project were evaluated for occurrence of dementia over 9 years. A total of 1,070 cognitively unimpaired subjects were also followed using amnestic mild cognitive impairment (aMCI) and other cognitive impairment, no dementia (OCIND) definitions. To correct the observed incidence rates for attrition due to death, cognitive status for subjects lost due to death was imputed using information on previous cognitive and health status. Observed and corrected incidence rates (IR) and 95% CIs were calculated with the person-years method, using Poisson distribution. RESULTS: Incidence rates per 1,000 person-years were as follows: dementia IR = 70.4 (64.0 to 77.4); aMCI observed IR = 11.4 (8.6 to 15.1), corrected IR = 13.7 (10.3 to 18.2); OCIND observed IR = 33.8 (28.7 to 39.8), corrected IR = 42.1 (36.5 to 48.6). Both aMCI and OCIND incidence increased with advancing age. Observed incidence of aMCI and OCIND together was similar to that of dementia at age 75 to 79 but lower at more advanced ages. However, the cognitive impairment incidence after age 79 increased substantially when the estimates were corrected for attrition due to death during follow-up. CONCLUSIONS: Non-dementia cognitive impairment is common and often underestimated in population studies that do not adjust for attrition.

Influence of comorbidity and cognitive status on instrumental activities of daily living in amnestic mild cognitive impairment: results from the ReGAl project.

OBJECTIVES: To investigate whether amnestic mild cognitive impairment (aMCI) is characterised by restriction in instrumental activities of daily living (IADL). Further, to examine the role of comorbidity and cognitive performance on IADL changes in aMCI subjects. METHODS: The study included 132 subjects with aMCI and 249 subjects with no cognitive impairment (NCI), consecutively enrolled as outpatients in a multicentric Italian clinical-based study, the ReGAl Project. All subjects underwent a comprehensive evaluation including clinical examination, laboratory screening, neuroimaging and cognitive and behavioral assessments. Functional status was evaluated by the Lawton's Instrumental Activities of Daily Living (IADL) scale. Comorbidity was evaluated by the Cumulative Illness Rating Scale (CIRS). Cognitive evaluation included tests assessing episodic memory, language, attention/executive functioning and praxis, as well as the the Mini-Mental State Examination (MMSE) as a measure of global cognition. RESULTS: Subjects with aMCI had higher IADL changes than NCI. Among IADL items, aMCI subjects showed a significant impairment in shopping, taking drugs, and handling economy; however also NCI had minor IADL changes regarding cooking, washing and cleaning. IADL restriction in aMCI subjects was significantly associated with cognitive performance, mainly related to executive functioning, but not with comorbidity. On the contrary, in NCI sensory impairment accounts for slight IADL changes. CONCLUSION: In aMCI subjects a mild degree of cognitive deterioration has a stronger impact on IADL than somatic comorbidity. Current diagnostic criteria for MCI should include a mild impairment in IADL.

Interictal executive dysfunction in migraineurs without aura: relationship with duration and intensity of attacks.

Subjects with migraine are at increased risk of subcortical white matter lesions (WML). Reports of cognitive testing in adults with migraine have yielded inconsistent results. We performed a cross-sectional study to assess whether migraine without aura (MwA) is associated with impairment in executive functioning, a typical cognitive correlate of subcortical WML. Forty-five subjects with MwA and 90 controls, matched for age and education, underwent a cognitive battery of tests evaluating executive functions. The following migraine characteristics were collected: age at onset and length of migraine history, and frequency, duration and intensity of attacks. Subjects with MwA performed significantly lower than controls in tests evaluating complex, multifactorial executive functions. After multiple adjustments, the duration and intensity of migraine attacks significantly predicted cognitive disturbances. In the interictal phase of MwA there is evidence of mild executive dysfunction. The cumulative effects of repeated migraine attacks on prefronto-cerebellar loop probably account for our results.

Predictors of progression from mild cognitive impairment to Alzheimer disease.

OBJECTIVE: To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI). METHOD: We followed 185 persons with no cognitive impairment and 47 with MCI (amnestic and multidomain), ages 75 to 95, from the population-based Kungsholmen Project, Stockholm, Sweden, for 3 years. Three types of neuropsychiatric symptoms were assessed at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptomatology. AD at 3-year follow-up was diagnosed according to Diagnostic and Statistical Manual for Mental Disorders-III-R criteria. RESULTS: Psychiatric symptoms occurred more frequently in persons with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in cognitively intact elderly individuals (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of persons with both MCI and anxiety symptoms, 83.3% developed AD over follow-up vs 6.1% of cognitively intact persons and 40.9% persons who had MCI without anxiety. Among persons with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom (relative risk [RR] = 1.8 [1.2 to 2.7] per symptom). Conversely, among cognitively intact subjects, only symptoms of depressive mood were related to AD development (RR = 1.9 [1.0 to 3.6] per symptom). CONCLUSIONS: The predictive validity of mild cognitive impairment (MCI) for identifying future Alzheimer disease (AD) cases is improved in the presence of anxiety symptoms. Mood-related depressive symptoms (dysphoria, suicidal ideation, etc.) in preclinical AD might be related to the neuropathologic mechanism, as they appear preclinically in persons both with and without MCI.