Evidence of plasma biomarkers indicating high risk of dementia in cognitively normal subjects.

Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) assays were utilized to assay plasma Aß1-42 and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer's disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer's disease (AD, n = 65). Thirty-seven healthy controls (HCs) were enrolled. The measured concentrations of plasma Aß1-42 were 14.26 ± 1.42, 15.43 ± 1.76, 15.52 ± 1.60, 16.15 ± 1.05, 16.52 ± 0.59, 15.97 ± 0.54 and 20.06 ± 3.09 pg/mL in HC, PS, ADFH, diabetes, ESRD, OSA and AD groups, respectively. The corresponding concentrations of plasma T-Tau were 15.13 ± 3.62, 19.29 ± 8.01, 17.93 ± 6.26, 19.74 ± 2.92, 21.54 ± 2.72, 20.17 ± 2.77 and 41.24 ± 14.64 pg/mL. The plasma levels of Aß1-42 and T-Tau in were significantly higher in the PS, ADFH, diabetes, ESRD and OSA groups than controls (Aß1-42 in PS: 15.43 ± 1.76 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.005; T-Tau in PS: 19.29 ± 8.01 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in ADFH: 15.52 ± 1.60 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ADFH: 17.93 ± 6.26 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in diabetes: 16.15 ± 1.05 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in diabetes: 19.74 ± 2.92 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in ESRD: 16.52 ± 0.59 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ESRD: 21.54 ± 2.72 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in OSA: 15.97 ± 0.54 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in OSA: 20.17 ± 2.77 vs. 15.13 ± 3.62 pg/mL, p < 0.001). This evidence indicates the high risk for dementia in these groups from the perspective of plasma biomarkers.

Assessment of High Risk for Alzheimer's Disease Using Plasma Biomarkers in Subjects with Normal Cognition in Taiwan: A Preliminary Study.

BACKGROUND: In Alzheimer's disease (AD), cognitive impairment begins 10-15 years later than neurodegeneration in the brain. Plasma biomarkers are promising candidates for assessing neurodegeneration in people with normal cognition. It has been reported that subjects with the concentration of plasma amyloid-ß 1-42×total tau protein higher than 455 pg2/ml2 are assessed as having a high risk of amnesic mild impairment or AD, denoted as high risk of AD (HRAD). OBJECTIVE: The prevalence of high-risk for dementia in cognitively normal controls is explored by assaying plasma biomarkers. METHODS: 422 subjects with normal cognition were enrolled around Taiwan. Plasma Aß1-40, Aß1-42, and T-Tau levels were assayed using immunomagnetic reduction to assess the risk of dementia. RESULTS: The results showed that 4.6% of young adults (age: 20-44 years), 8.5% of middle-aged adults (age: 45-64 years), and 7.3% of elderly adults (age: 65-90 years) had HRAD. The percentage of individuals with HRAD dramatically increased in middle-aged and elderly adults compared to young adults. CONCLUSION: The percentage of HRAD in cognitively normal subjects are approximately 10%, which reveals that the potentially public-health problem of AD in normal population. Although the subject having abnormal levels of Aß or tau is not definitely going on to develop cognitive declines or AD, the risk of suffering cognitive impairment in future is relatively high. Suitable managements are suggested for these high-risk cognitively normal population. Worth noting, attention should be paid to preventing cognitive impairment due to AD, not only in elderly adults but also middle-aged adults.

Investigation of the Number of Tests Required for Assaying Plasma Biomarkers Associated with Alzheimer's Disease Using Immunomagnetic Reduction.

INTRODUCTION: Concentrations of plasma biomarkers associated with Alzheimer's disease have been reported to be as low as several tens of picograms/milliliter (pg/ml). However, in assays measuring these biomarkers, it is likely that repeated measurements are necessary to obtain reliable values. METHODS: We performed assays as a single test or as duplicate, quadruplicate, fivefold and tenfold repeated tests, on samples spiked with different concentrations of amyloid ß 1-40 (Aß1-40; 1-1000 pg/ml), Aß1-42 (1-30,000 pg/ml) and total Tau protein (T-Tau; 0.1-1000 pg/ml), with the aim to to calculate the coefficients of variation (CVs). RESULTS: The results demonstrated common changes in the CVs with changes in the number of tests for a given sample: the CVs decreased with increases in the number of tests from one to ten. All CV values were distributed within the range of 0.35 to 15.5%; as such, the CV values were all lower than the acceptable value of 20%. CONCLUSION: Based on this study, a single assay of Aß1-40, Aß1-42 and T-Tau, respectively, provides reliable results in terms of the measurement of that plasma biomarker.

Urban-rural differences in the prevalence and correlates of mild cognitive impairment in community-dwelling older adults in Taiwan: The EMCIT study.

BACKGROUND: Taiwan is a rapidly aging society. The elderly with mild cognitive impairment (MCI) have increased risk of dementia, and this is a population-based report using standard neuropsychological tests and expert consensus diagnosis to assess the MCI prevalence and its associated factors in Taiwan. METHOD: The Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT) is a community-based, prospective cohort study. Independently-living individuals aged ≧60 years in a rural area (n = 122) and in an urban area (n = 348) of New Taipei City, Taiwan, completed detailed neuropsychological tests at the cohort baseline. Diagnosis of MCI was ascertained through expert consensus based on 2011 NIA-AA criteria. RESULTS: Of 470 participants recruited between 2017 and 2019 (mean age 71.2 ± 5.4 years), the prevalence of MCI was higher in the rural area than in the urban area (25.1% vs. 10.8%, p < 0.001) after standardized for age, gender, and level of education. Having lower education and having depression symptoms were consistently associated with increased risk of MCI in both urban and rural areas (p < 0.05). Being male and diabetes were additionally associated with MCI prevalence in urban areas. CONCLUSION: In this community-based prospective cohort study in Taiwan, the prevalence of MCI in the rural community was much higher than that in the urban community. Different strategies may be needed to targeted different types of communities.

Nanoparticle-based immunomagnetic assay of plasma biomarkers for differentiating dementia and prodromal states of Alzheimer's disease - A cross-validation study.

Blood-based biomarker assays of plasma ß-amyloid (Aß) and tau have the advantages of cost-effective and less invasive for the diagnosis of Alzheimer's disease (AD). We used two independent cohorts to cross-validate the clinical use of the nanoparticle-based immunomagnetic assay of plasma biomarkers to assist in the differential diagnosis of early AD. There were in total 160 subjects in the derivation cohort, and 242 in the validation cohort both containing controls, mild cognitive impairment due to AD and AD dementia diagnosed according to the 2011 NIA-AA guidelines. The cutoff value for plasma Aß1-42 (16.4 pg/ml) performed the best in differentiating between controls and patients with prodromal or clinical AD, with 92.5% for positive percent agreement (PPA), negative percent agreement (NPA), and overall rate of agreement (ORA). Aß1-42 × tau (642.58) was useful for separating patients with dementia and prodromal states of AD, with 84.9% PPA, 78.8% NPA and 83% ORA.

Corrigendum: Age-Dependent Relationship Between Plasma Aß40 and Aß42 and Total Tau Levels in Cognitively Normal Subjects.

[This corrects the article DOI: 10.3389/fnagi.2019.00222.].

Age-Dependent Relationship Between Plasma Aß40 and Aß42 and Total Tau Levels in Cognitively Normal Subjects.

Both amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with Alzheimer's disease (AD). However, the constituents of these hallmarks, amyloid beta (Aß) 40, Aß42, and total Tau (t-Tau), have been detected in the blood of cognitively normal subjects by using an immunomagnetic reduction (IMR) assay. Whether these levels are age-dependent is not known, and their interrelation remains undefined. We determined the levels of these biomarkers in cognitively normal subjects of different age groups. A total of 391 cognitively normal subjects aged 23-91 were enrolled from hospitals in Asia, Europe, and North America. Healthy cognition was evaluated by NIA-AA guidelines to exclude subjects with mild cognitive impairment (MCI) and AD and by cognitive assessment using the Mini Mental State Examination and Clinical Dementia Rating (CDR). We examined the effect of age on plasma levels of Aß40, Aß42, and t-Tau and the relationship between these biomarkers during aging. Additionally, we explored age-related reference intervals for each biomarker. Plasma t-Tau and Aß42 levels had modest but significant correlations with chronological age (r = 0.127, p = 0.0120 for t-Tau; r = -0.126, p = 0.0128 for Aß42), ranging from ages 23 to 91. Significant positive correlations were detected between Aß42 and t-Tau in the groups aged 50 years and older, with Rho values ranging from 0.249 to 0.474. Significant negative correlations were detected between Aß40 and t-Tau from age 40 to 91 (r ranged from -0.293 to -0.582) and between Aß40 and Aß42 in the age groups of 30-39 (r = -0.562, p = 0.0235), 50-59 (r = -0.261, p = 0.0142), 60-69 (r = -0.303, p = 0.0004), and 80-91 (r = 0.459, p = 0.0083). We also provided age-related reference intervals for each biomarker. In this multicenter study, age had weak but significant effects on the levels of Aß42 and t-Tau in plasma. However, the age group defined by decade revealed the emergence of a relationship between Aß40, Aß42, and t-Tau in the 6th and 7th decades. Validation of our findings in a large-scale and longitudinal study is warranted.

Patterns of Chinese medicine use in prescriptions for treating Alzheimer's disease in Taiwan.

BACKGROUND: Certain Chinese medicine (CM) herbs and acupuncture may protect against Alzheimer's disease (AD). However, there is a lack of research regarding the use of CM in patients with AD. The aim of this study was to investigate CM usage patterns in patients with AD, and identify the Chinese herbal formulae most commonly used for AD. METHODS: This retrospective, nationwide, population-based cohort study was conducted using a randomly sampled cohort of one million patients, selected from the National Health Insurance Research Database between 1997 and 2008 in Taiwan. CM use and the top ten most frequently prescribed formulae for treating AD were assessed, including average formulae dose and frequency of prescriptions. Demographic characteristics, including sex, age and insurance level were examined, together with geographic location. Existing medical conditions with the behavioral and psychological symptoms of dementia, and medications associated with CM were also examined. Factors associated with CM use were analyzed by multiple logistic regressions. RESULTS: The cohort included 1137 newly diagnosed AD patients, who were given conventional treatment for AD between 1997 and 2008. Among them, 78.2 % also used CM treatments, including Chinese herbal remedies, acupuncture and massage manipulation. Female patients (aOR 1.57 with 95 % CI 1.16-2.13) and those living in urban areas (aOR 3.00 with 95 % CI 1.83-4.90 in the middle of Taiwan) were more likely to use CM. After adjusting for demographic factors, AD patients suffering from the behavioral and psychological symptoms of dementia were more likely to seek CM treatment than those with no symptoms (aOR 2.26 with 95 % CI 1.48-3.43 in patients suffering more than three symptoms). Bu-Zhong-Yi-Qi-Tang and Ji-Sheng-Shen-Qi-Wan were the two formulae most frequently prescribed by CM practitioners for treating AD. CONCLUSION: Most people with AD who consumed herbal products used supplement qi, nourish the blood, and quiet the heart spirit therapy as complementary medicines to relieve AD-related symptoms, in addition to using standard anti-AD treatments.

Clinical Dementia Rating Scale Detects White Matter Changes in Older Adults at Risk for Alzheimer's Disease.

This study investigated the putative changes in regional gray matter and cingulum bundle segments in mild cognitive impairment (MCI) by using two diagnostic criteria. Participants comprised 50 older adults with MCI and 22 healthy older controls (HC). The older adults with MCI were further divided into two groups defined by a global Clinical Dementia Rating (CDR) score of 0.5 and with (the CDR/NPT MCI group) or without (the CDR MCI group) objective cognitive impairments determined using neuropsychological tests (NPTs). Comparable regional gray matter integrity was observed among the three groups. However, the integrity of the right inferior segment of the cingulum bundle in the two MCI groups was more reduced than that in the HC group, and the CDR/NPT MCI group exhibited additional disruption in the left inferior cingulum bundle. The results also demonstrated that neuropsychological measures have greater predictive value for changes in white matter beyond the contribution of an informant-based instrument alone. Overall, the findings confirm the utility of informant-based assessment in detecting microstructural brain changes in high-risk older adults, even before objective cognitive impairment is evident. The findings also suggest that combining the neuropsychological measures with the informant-based assessment provided the greatest predictive value in assessing white matter disruption. The essential role of the white matter measurement as a biomarker for detecting individuals at a high risk of developing dementia was highlighted.

Investigations of kanuka and manuka essential oils for in vitro treatment of disease and cellular inflammation caused by infectious microorganisms.

BACKGROUND: Diseases caused by infectious and inflammatory microorganisms are among the most common and most severe nosocomial diseases worldwide. Therefore, developing effective agents for treating these illnesses is critical. In this study, essential oils from two tea tree species, kanuka (Kunzea ericoides) and manuka (Leptospermum scoparium), were evaluated for use in treating diseases and inflammation caused by microorganism infection. METHODS: Isolates of clinically common bacteria and fungi were obtained from American Type Culture Collection and from Kaohsiung Veterans General Hospital. Minimum inhibitory concentrations for Trichosporon mucoides, Malassezia furfur, Candida albicans, and Candida tropicalis were determined by the broth microdilution method with Sabouraud dextrose broth. The antibacterial susceptibility of Staphylococcus aureus, Streptococcus sobrinus, Streptococcus mutans, and Escherichia coli were determined by the broth microdilution method. A human acute monocytic leukemia cell line (THP-1) was cultured to test the effects of the essential oils on the release of the two inflammatory cytokines, tumor necrosis factor-α and interleukin-4. RESULTS: Multiple analyses of microorganism growth confirmed that both essential oils significantly inhibited four fungi and the four bacteria. The potent fungicidal properties of the oils were confirmed by minimum inhibitory concentrations ranging from 0.78% to 3.13%. The oils also showed excellent bactericidal qualities with 100% inhibition of the examined bacteria. In THP-1 cells, both oils lowered tumor necrosis factor-α released after lipopolysaccharide stimulation. Finally, the antimicrobial and anti-inflammatory effects of the oils were obtained without adversely affecting the immune system. CONCLUSION: These results indicate that the potent antimicroorganism and anti-inflammation properties of kanuka and manuka essential oils make them strong candidates for use in treating infections and immune-related disease. The data confirm the potential use of kanuka and manuka extracts as pharmaceutical antibiotics, medical cosmetology agents, and food supplements.

Regional cingulum disruption, not gray matter atrophy, detects cognitive changes in amnestic mild cognitive impairment subtypes.

Amnestic mild cognitive impairment (aMCI), which has a high risk of progression to Alzheimer's disease (AD), can be classified into single domain (S-aMCI) and multiple domain (M-aMCI) subtypes. We investigated the integrity of regional gray matter and segments of the cingulum bundle with diffusion spectrum imaging tract-specific analysis, and their relationships to neuropsychological functioning, in 46 individuals with aMCI (S-aMCI n = 24; M-aMCI n = 22) and 36 healthy controls (HC). Results demonstrated that although both aMCI groups were impaired on all memory measures relative to HCs, the M-aMCI group demonstrated worse performance on paired association memory and on selective executive function relative to the S-aMCI group. The two aMCI groups did not show significant atrophy in regional gray matter indices as compared to the HC group, but the M-aMCI group showed significant disruption in white matter of the left anterior and inferior cingulum bundles relative to the S-aMCI and HC groups. Furthermore, disruption in the inferior cingulum bundles was significantly associated with executive function and attention/processing speed in all aMCI participants above and beyond the contribution of bilateral hippocampal volumes. Overall, these results indicate that the degeneration of cingulum fibers did not appear to arise from degeneration of the corresponding cerebral cortex. It also suggests relatively greater sensitivity of a white matter biomarker and comprehensive neuropsychological evaluation over gray matter biomarkers in early detection of AD.

A novel XK gene mutation in a Taiwanese family with McLeod syndrome.

McLeod syndrome is one subtype of rare neuroacanthocytosis syndromes characterized by misshapen red blood cells and progressive degeneration of the basal ganglia. It is an X-linked recessive disorder with mutation in the XK gene of the Kell blood group system with multisystem involvements. Concerning the movement disorders, its dyskinesias are various and difficult to differentiate from those in Huntington's disease or other hyperkinetic movement disorders. In this report, we described a 62-year-old male patient presenting with insidious myalgia and muscle fatigue. Progressive motor restlessness and toes choreoathetosis were noted. Previously, he had chronic psychotic disorder with irregular treatment for 14 years. The laboratory tests revealed elevated creatine phosphokinase and acanthocytes (36.3%). The electrophysiological test demonstrated an axonal type polyneuropathy. The neuroimaging of brain showed striatal degeneration. Genetic analysis revealed a nonsense hemizygous mutation c.154C>T (p.Gln52X) at exon 1 of XK gene. The genetic counseling of his family revealed one elder brother carrying the same mutation and showing a similar but very mild syndrome. Several offspring were the asymptomatic carriers. We suggest that for a patient with multiple system disorders including dyskinetic movement disorders, psychiatric symptoms, polyneuropathy, and elevated CPK, a genetic test for XK gene mutation is highly indicated to confirm the McLeod syndrome and to guide the possible therapy.

Altered source-based EEG coherence of resting-state sensorimotor network in early-stage Alzheimer's disease compared to mild cognitive impairment.

Although the altered coherence between cortical areas in Alzheimer's disease (AD) has been widely studied, it remains unclear whether the source-based coherence measures within sensorimotor network show significant difference between mild cognitive impairment (MCI) and AD. In the present study, resting-state electroencephalographic signals were recorded from 21 MCI and 21 mild AD patients. The spectral power and coherence in the sensorimotor areas were analyzed using the minimum norm estimate (MNE) combined with fast Fourier transform and coherence analysis in delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-25 Hz), and gamma (25-40 Hz) bands. Our results indicated that source-based coherence in AD showed increased delta coherences between the bilateral precentral, left supplementary motor area (SMA) and right precentral, and left SMA and right postcentral areas. However, no significant difference of spectral powers was observed between AD and MCI. To conclude, the phenotype conversion from MCI to AD may be associated with an altered connectivity of the sensorimotor cortical network. This is a promising finding; however, further large-scale studies are needed.

Altered oscillation and synchronization of default-mode network activity in mild Alzheimer's disease compared to mild cognitive impairment: an electrophysiological study.

Some researchers have suggested that the default mode network (DMN) plays an important role in the pathological mechanisms of Alzheimer's disease (AD). To examine whether the cortical activities in DMN regions show significant difference between mild AD from mild cognitive impairment (MCI), electrophysiological responses were analyzed from 21 mild Alzheimer's disease (AD) and 21 mild cognitive impairment (MCI) patients during an eyes closed, resting-state condition. The spectral power and functional connectivity of the DMN were estimated using a minimum norm estimate (MNE) combined with fast Fourier transform and imaginary coherence analysis. Our results indicated that source-based EEG maps of resting-state activity showed alterations of cortical spectral power in mild AD when compared to MCI. These alterations are characteristic of attenuated alpha or beta activities in the DMN, as are enhanced delta or theta activities in the medial temporal, inferior parietal, posterior cingulate cortex and precuneus. With regard to altered synchronization in AD, altered functional interconnections were observed as specific connectivity patterns of connection hubs in the precuneus, posterior cingulate cortex, anterior cingulate cortex and medial temporal regions. Moreover, posterior theta and alpha power and altered connectivity in the medial temporal lobe correlated significantly with scores obtained on the Mini-Mental State Examination (MMSE). In conclusion, EEG is a useful tool for investigating the DMN in the brain and differentiating early stage AD and MCI patients. This is a promising finding; however, further large-scale studies are needed.

Improvement of diagnostic rate of carpal tunnel syndrome with additional median-to-ulnar comparative nerve conduction studies.

PURPOSE: The aim of this study is to assess whether additional median -to-ulnar comparative tests will improve the diagnostic rate of carpal tunnel syndrome (CTS). METHODS: We recruited 248 hands of 162 CTS patients, and 166 hands of 83 controls. One hundred and sixty-eight (68%) symptomatic hands had abnormal median distal latencies or palm-wrist latencies. We performed three additional comparative tests in the remaining symptomatic hands and the non-CTS hands. The first test compared median distal motor latency (MDL) recorded from the second lumbrical muscle (2L) and ulnar distal latency recorded from interossei muscles (INT) (2L-INT). The second test compared median and ulnar antidromic sensory latencies (MS-US). And the third test compared median and ulnar nerve latencies in the palm-to-wrist segment (PM-PU). RESULTS: In control subjects, upper limits of median-to-ulnar differences were: 2L-INT= 0.4 ms, MS-US= 0.5 ms, PM-PU= 0.4 ms. In CTS patients with normal conventional electrodiagnostic methods, MS-US difference showed the lowest sensitivity (21.3%). The diagnostic sensitivity of 2L-INT was 27.5% and PM-PU 47.5%. With PM-PU test, additional 15.3% diagnostic rate could be got. CONCLUSION: For CTS patients with normal results from the standard methods, PM-PU is a good additional comparative test to further improve diagnostic rate.

A pilot study of the telecare medical support system as an intervention in dementia care: the views and experiences of primary caregivers.

BACKGROUND: As a progressive degenerative illness, dementia can reveal itself through a variety of symptoms such as intellectual deterioration, loss of recent memory, loss of cognitive ability, and psychological and behavioral problems. The telecare medical support system (TMSS) has been a part of dementia care in many countries for many years. Although worth considering, the TMSS model is difficult to directly implement in Taiwan because of cultural and social issues. PURPOSE: This study explores the ease of use and usefulness of TMSS from the perspective of primary caregivers and assesses the benefits of TMSS in home dementia care. METHODS: We used a qualitative research method to explore the experience and perceptions of 30 primary caregivers who each used TMSS for 6 months in dementia care. Data were collected using 1-hour in-depth interviews. Four senior nurses conducted the content analysis. RESULTS: Approximately two thirds (63.3%) of the participants were primary caregivers of patients with Alzheimer's disease in the mild to medium stage of their illness. After using TMSS for the 6-month study period, participants held generally positive views of its usefulness and ease of use. Participants generally appreciated the ability of TMSS to self-diagnose care recipient conditions; provide reminders, care, and emotional support; and help stabilize the care recipient's condition and emotions. CONCLUSIONS: We showed TMSS as an effective tool that helps reduce primary caregiver isolation and uncertainty and provides round-the-clock care management and safety checks using advanced technology and a professional care team. TMSS can effectively enhance dementia care.

Midlife risk factors for subtypes of dementia: a nested case-control study in Taiwan.

OBJECTIVE: To identify the midlife risk factors for subtypes of dementia newly developed later in life. METHODS: A nested case-control study was conducted on 157 demented cases and 628 comparison cases selected from 40,636 men and women who were enrolled from 1982 to 1992. Four comparison cases were frequency-matched on age, time at enrollment (within 6 months), gender, and residential township. Midlife risk factors included vascular risk factors (body mass index [BMI], total cholesterol, total triglycerides, blood glucose, cerebrovascular accident [CVA] history, diabetes mellitus history, and hypertension history), cigarette smoking, and alcohol consumption. Dementia assessments were ascertained through the computerized data linkage from National Health Insurance Database from 2000 to 2002 and clinically confirmed by neurologists or psychiatrists. Conditional logistic regression analysis was used to estimate the matched odds ratio (OR) and its 95% confidence intervals (CI) for each risk factor. RESULTS: A J-shaped relationship was observed between BMI (kg/m(2)) and dementia. The multivariate-adjusted ORs (95% CI) of developing dementia were 1.84 (1.02-3.33), 1.87 (1.08-3.23) and 2.44 (1.39-4.28), respectively, for BMIs of <20.5, 23.0-25.4, >or=25.5 compared with a BMI of 20.5-22.9 as the referent group (OR = 1.0). Similar findings were observed for Alzheimer disease (AD) and vascular dementia (VaD). The association between obesity (BMI >or=25.5) and both AD and VaD was statistically significant among cigarette smokers but not among nonsmokers. Additionally, history of CVA was a significant risk factor for VaD, but not for AD. CONCLUSION: Being underweight, being overweight, and a cerebrovascular accident in midlife may increase the risk of dementia in late life.

Psychiatric morbidity in dementia patients in a neurology-based memory clinic.

The behavioral and psychological symptoms of dementia (BPSD) often present major problems for patients and their caregivers. In the past, neurologists paid less attention to such symptoms than to the cognitive symptoms of dementia. This prospective study investigated the prevalence of psychiatric morbidity in a neurology-based memory clinic and the stress of caregivers. Our patients with dementia were found to have a high prevalence of BPSD. The most frequent were anxiety, apathy, and delusion; the most distressing to caregivers were agitation, anxiety, delusion, and sleep disturbance. Using Clinical Dementia Rating (CDR), we compared BPSD between patients with mild dementia and those with moderate dementia. Only hallucinations and agitation were different significantly. Moderate dementia patients experienced these symptoms more frequently. The high prevalence of these symptoms might be explained by the fact that the cognitive symptoms were neglected or no enough information were received by many family members of patients with dementia until their own life quality was interfered and then they began to seek medical help. These symptoms and their effect of caregiver distress can be effectively reduced by pharmacologic and nonpharmacoloic managements, caregiver-focused training and education. They can be better approached by assessing neuropsychiatric symptoms regularly, educating the general population better, and treating these patients earlier.

Sensory nerve conduction studies of the superficial peroneal nerve in L5 radiculopathy.

BACKGROUND: Theoretically, sensory nerve action potential (SNAP) of the superficial peroneal nerve (SPN) should be preserved when L5 roots are damaged. Previous study indicated that SNAP of SPN was lost or reduced in amplitude in patiens with L5 radiculopathy. To address this issue, this study compared results of SPN sensory conduction studies between healthy subjects and patients with L5 radiculopathy. METHODS: Ninety-four healthy subjects were enrolled and assigned to two age groups: group I (< or = 60 years, n=61) and group II (> 60 years, n=33). Forty-one patients with unilateral L5 radiculopathy were enrolled by our electrodiagnostic laboratory between July 2000 and July 2003 and assigned to two age groups: 60 years or below (n=19) and above 60 years (n=22). RESULTS: SPN response was found to be abnormal in only 1.6% of group I healthy subjects, but absent or abnormal SPN response was noted in 21.1% of patients with L5 radiculopathy of the same age group (p=0.01). However, a greater proportion of (27.3%) our healthy subjects above 60 years had abnormal SPN responses. This proportion was similar to that of patients with L5 radiculopathy and abnormal SPN response (31.8%) (p=0.72). CONCLUSIONS: SPN sensory responses are reliably obtained in most healthy subjects under 60 years of age. Absence of SNAP or reduced SNAP amplitude of SPN on the side of their lesions did not necessarily exclude the diagnosis of L5 radiculopathy in the patients under 60 years of age.

Lobar cerebral hemorrhage from amyloid angiopathy: clinical, neuroimaging, pathologic and outcome correlations.

Cerebral amyloid angiopathy (CAA) contributes to sporadic lobar intracerebral hemorrhage in older patients, especially those who are more than 70 years old. In clinical practice, a diagnosis of CAA refers to the Boston Criteria, which requires that "definitive" cases be confirmed by pathologic evidence at autopsy. A "Probable" case, means that there is clinical support and that pathologic evidence is available by biopsy from the craniotomy for patients with severe lobar intracerebral hemorrhage. Cerebral amyloid that is deposited in cortical vessels is revealed by apple-green birefringence under polarized light using Congo-red stain. Rebleeding after a first primary intracerebral hemorrhage is common. This paper describes five cases of aged patients with lobar cerebral hemorrhage and craniotomy with hematoma evacuation and biopsy. Pathological results all showed amyloid angiopathy. Various outcomes are discussed, and the literature is reviewed. Findings show that although patients with CAA were at high risk of recurrent hemorrhage after surgery, the mortality rate was relatively low despite the severity of lobar intracerebral hemorrhage.