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Background: For those outpatients who were consulted for memory loss, the Japanese version of University of Pennsylvania Smell Identification Test (UPSIT‐J) was performed to examine olfactory function. In the same way, the revised version of Hasegawa Dementia Scale, Mini Mental State Examination, Clinical Dementia Rating and brain magnetic resonance imaging were used to investigate the cognitive function. In the present study, we evaluated the olfactory function of elderly subjects, including those with dementia, by means of UPSIT‐J and we examined their characteristics. Methods: The characteristics of dementia as Alzheimer type group (AD.G), mixed type group (MixD.G), vascular type group (VaD.G), dementia with Lewy bodies group (DLB.G) and the groups which had no dementia as low score group (LS.G), high score group (HS.G), and healthy group (H.G), were examined. Results: The numbers of olfactory discriminating scores (nODS) were significantly lower in all the dementia groups than in all the LS.G, HS.G and the H.G. No significant difference was observed in nODS between AD.G and DLB.G. The rate of nODS with less than five scores were as follows: AD.G (80.1%), MixD.G (91.5%), VaD.G (63.1%), DLB.G (89.6%), LS.G (50.8%), HS.G (18.6%), H.G (15.6%). A significant positive correlation was found between nODS and Hasegawa Dementia Scale and Mini Mental State Examination scores (r = 0.567, r = 0.532, respectively), which was significant negatively correlated for Clinical Dementia Rating (r = −0.578). A significant negative correlation was observed between nODS and Z score of voxel‐based specific regional analysis for Z score of Alzheimer's disease (VSRAD) (r = 0.463). Conclusion: nODS showed a significant correlation between cognitive function tests and brain atrophy level. These results indicate that UPSIT‐J is considered a psycho‐physiological index useful for the diagnosis and early detection of dementia. [ABSTRACT FROM AUTHOR]

Due to the high prevalence of different levels of memory disorders and amnesia, many psychiatry and psychology referrals are due to the fear of diseases that cause dementia, including Alzheimer's disease. However, many of these disorders have internal causes and can be classified as functional cognitive disorders. Although the diagnosis of cognitive disorder is made by ruling out organic causes, it is difficult to diagnose functional disorders, thus most of these disorders are not diagnosed. It has been determined that depression, anxiety and behavioral disorders can be precursors of mild cognitive impairment, but it has not been determined whether functional cognitive impairment can also be a trigger or precursor for organic cognitive disorders related to dementia. The typical form of functional cognitive disorder overlaps with the components of attention and concentration. The coexistence of these disorders with depression can make the diagnosis of functional cognitive disorders more difficult. Therefore, it is important to rule out pseudodementia due to depression before making such a diagnosis. Since functional cognitive impairment occur in the midlife period, these disorders are differentially diagnosed with early-onset neurodegenerative disorders. Regardless of the research conducted in the field of diagnosing functional cognitive disorders, no definitive diagnostic criteria have been determined for these disorders, and the long-term prognosis of these disorders is also unknown.

Due to the high prevalence of different levels of memory disorders and amnesia, many psychiatry and psychology referrals are due to the fear of diseases that cause dementia, including Alzheimer's disease. However, many of these disorders have internal causes and can be classified as functional cognitive disorders. Although the diagnosis of cognitive disorder is made by ruling out organic causes, it is difficult to diagnose functional disorders, thus most of these disorders are not diagnosed. It has been determined that depression, anxiety and behavioral disorders can be precursors of mild cognitive impairment, but it has not been determined whether functional cognitive impairment can also be a trigger or precursor for organic cognitive disorders related to dementia. The typical form of functional cognitive disorder overlaps with the components of attention and concentration. The coexistence of these disorders with depression can make the diagnosis of functional cognitive disorders more difficult. Therefore, it is important to rule out pseudodementia due to depression before making such a diagnosis. Since functional cognitive impairment occur in the midlife period, these disorders are differentially diagnosed with earlyonset neurodegenerative disorders. Regardless of the research conducted in the field of diagnosing functional cognitive disorders, no definitive diagnostic criteria have been determined for these disorders, and the long-term prognosis of these disorders is also unknown. [ABSTRACT FROM AUTHOR]

Background: Donepezil is approved for treatment of dementia of the Alzheimer type and is currently available only in tablet forms in the United States.Objective: To compare steady-state pharmacokinetics of once-weekly 10-mg/d and 5-mg/d Corplex™ donepezil transdermal delivery systems (TDS) with once-daily 10-mg oral donepezil.Methods: Open-label, randomized, crossover study (NCT04617782) enrolled healthy participants aged 18-55 years. All participants received 5-mg/d donepezil TDS during the 5-week Period 1, followed by 10-mg/d TDS or 10-mg/d oral donepezil in the 5-week Period 2; treatments were switched in Period 3. Bioequivalence was assessed at steady state on Week 5.Results: All 60 enrolled participants received 5-mg/d TDS, 55 received 10-mg/d TDS, and 56 received oral donepezil. Adjusted geometric mean ratio (% [90% CI]) for maximum plasma concentration and area under the plasma concentration versus time curve (0-168 h) were 88.7 (81.7-96.2) and 108.6 (100.5-117.4) for 10-mg/d and 86.1 (79.8-92.9) and 105.3 (97.6-113.6) for dose-normalized 5-mg/d TDS and were generally within the 80% -125% range for establishing bioequivalence with oral donepezil. Skin adhesion was similar for both TDSs (>80% of patches remaining ≥75% adhered throughout the wear period). Overall incidence of adverse events (AEs) was similar across treatments. Compared with 10-mg/d TDS, oral donepezil was associated with higher incidence of gastrointestinal and nervous system AEs (14.5% versus 53.6% and 14.5% versus 30.4%, respectively).Conclusion: Donepezil TDSs are bioequivalent to oral donepezil at steady state and have a safety profile that supports their use in treating dementia of the Alzheimer type. [ABSTRACT FROM AUTHOR]

Abstract We examined whether symptoms of dementia are improved by olfactory nerve stimulation in Alzheimer type dementia patients. First, a stick‐type olfactory identification ability test was performed in patients with Alzheimer type dementia, to select patients without olfactory dysfunctions. Then, these patients were randomly assigned into the intervention (n = 19) and the control groups (n = 17). To evaluate the effects of olfactory nerve stimulation, we exposed the intervention group to a disinfecting ethanol with added aroma extracts from ceder and the control group to the ethanol without the added aroma extracts. Each group underwent the intervention for 8 weeks, cognitive and behavioral functions were evaluated before and after treatments using the Neuropsychiatric Inventory (NPI), the Japanese version of Zarit Caregiver Burden interview (J‐ZBI), and the Alzheimer's Disease Assessment Scale‐cognitive subscale (ADAS‐cog). A significant improvement was observed in the NPI score and J‐ZBI in the intervention group compared to the control group at 4 and 8 weeks. On the other hand, there was no significant difference in the score of ADAS‐cog. Exposure to cedar fragrance improved behavioral and psychological symptoms of dementia (BPSD) in Alzheimer type dementia and may reduce the burden of nursing care. In addition to its effectiveness, the procedure is simple and minimally invasive and would be a valuable non‐pharmaceutical treatment.

We examined whether symptoms of dementia are improved by olfactory nerve stimulation in Alzheimer type dementia patients. First, a stick‐type olfactory identification ability test was performed in patients with Alzheimer type dementia, to select patients without olfactory dysfunctions. Then, these patients were randomly assigned into the intervention (n = 19) and the control groups (n = 17). To evaluate the effects of olfactory nerve stimulation, we exposed the intervention group to a disinfecting ethanol with added aroma extracts from ceder and the control group to the ethanol without the added aroma extracts. Each group underwent the intervention for 8 weeks, cognitive and behavioral functions were evaluated before and after treatments using the Neuropsychiatric Inventory (NPI), the Japanese version of Zarit Caregiver Burden interview (J‐ZBI), and the Alzheimer's Disease Assessment Scale‐cognitive subscale (ADAS‐cog). A significant improvement was observed in the NPI score and J‐ZBI in the intervention group compared to the control group at 4 and 8 weeks. On the other hand, there was no significant difference in the score of ADAS‐cog. Exposure to cedar fragrance improved behavioral and psychological symptoms of dementia (BPSD) in Alzheimer type dementia and may reduce the burden of nursing care. In addition to its effectiveness, the procedure is simple and minimally invasive and would be a valuable non‐pharmaceutical treatment. [ABSTRACT FROM AUTHOR]

In this study, the aims were to assess the mental health state of carers for patients with Alzheimer-type dementia (AD) according to stage of disease and to collect data with the aim of determining precautions to reduce the load of the patient and disease on the carer. The study included 120 patients with stages determined, according to the clinical dementia rating scale (CDR), and 120 patient relatives above the age of 18 who cared for these patients every day, for the whole day or part of the day, and who accepted participation in the research. This prospective and cross-sectional study performed a detailed neurological examination of patients, and after completing the "personal information form" with the interviewer, each patient had CDR and mini-mental test (MMSE) applied to determine stage of dementia and physical state. Carers first completed the "personal information form" and then had the short symptom inventory (SSI) applied. According to the stage of patients, there were significant differences determined in the points for all sub-scales belonging to the SSI of carers. As the disease stage increased, all sub-scale points for the SSI increased. With the transition of disease stages from 0.5-1 to stage 2, from stage 2 to 3, and with the inverse reduction in MMT scores, the points obtained by carers on the SSI sub-scales increased. This data shows that with progressing disease stage, the load on the carer increases and mental health begins to dysfunction. [ABSTRACT FROM AUTHOR]

Background: In cognitively normal (CN) older adults, carriage of the apolipoprotein E (APOE) ɛ4 allele is associated with increased risk for dementia of the Alzheimer type (AD-dementia). It is unclear whether this occurs solely through APOEɛ4 increasing amyloid-β (Aβ) accumulation or through processes independent of Aβ.Objective: To determine the extent and nature to which APOEɛ4 increases risk for clinical disease progression in CN older adults.Methods: Data from the total (n = 765) and Aβ-imaged (n = 423) CN cohort in the Australian Imaging, Biomarker and Lifestyle (AIBL) Study of Ageing was analyzed using Cox proportional hazard models to estimate ɛ4 risk for clinical disease progression over a 72-month follow-up.Results: With Aβ status unknown and risk from demographic characteristics controlled, ɛ4 carriage increased risk for clinical disease progression over 72 months by 2.66 times compared to risk of non-ɛ4 carriage. Re-analysis with Aβ status included showed that abnormally high Aβ increased risk for clinical disease progression over 72 months by 2.11 times compared to risk of low Aβ. However, with Aβ level known, ɛ4 carriage was no longer predictive of clinical disease progression.Conclusion: In CN older adults, the risk of ɛ4 for clinical disease progression occurs through the effect of ɛ4 increasing Aβ levels. [ABSTRACT FROM AUTHOR]

In patients with different forms of dementia we compared serum and cerebrospinal fluid concentrations of α-tocopherol (vitamin-E), the major circulating lipid-soluble antioxidant, and neopterin, a product released from monocytic cells upon stimulation with interferon-γ. A significant inverse correlation was found between the concentrations of both compounds in the cerebrospinal fluid. The data point to a role of oxidative stress to reduce antioxidant levels in elderly demented patients with neurodegenerative diseases.

We examined whether conversion to dementia can be predicted by self-reported olfactory impairment and/or by an inability to identify odors. Common forms of dementia involve an impaired sense of smell, and poor olfactory performance predicts cognitive decline among the elderly. We followed a sample of 1529 participants, who were within a normal range of overall cognitive function at baseline, over a 10-year period during which 159 were classified as having a dementia disorder. Dementia conversion was predicted from demographic variables, Mini-Mental State Examination score, and olfactory assessments. Self-reported olfactory impairment emerged as an independent predictor of dementia. After adjusting for effects of other predictors, individuals who rated their olfactory sensitivity as “worse than normal” were more likely to convert to dementia than those who reported normal olfactory sensitivity (odds ratio [OR] = 2.17; 95% confidence interval [CI] [1.40, 3.37]). Additionally, low scores on an odor identification test also predicted conversion to dementia (OR per 1 point increase = 0.89; 95% CI [0.81, 0.98]), but these two effects were additive. We suggest that assessing subjective olfactory complaints might supplement other assessments when evaluating the risk of conversion to dementia. Future studies should investigate which combination of olfactory assessments is most useful in predicting dementia conversion. (JINS, 2014, 20, 1–9) [ABSTRACT FROM PUBLISHER]

The current study examined whether healthy older adults (OA) and individuals at the earliest stages of dementia of the Alzheimer's type (DAT) differ from younger adults (YA) and from each other on a simple, extended continuous tapping task using intervals (500 ms, 1000 ms, and 1500 ms) thought to differentially engage attentional control systems. OA groups sped up their tapping at the slowest target rate compared to the YA; this pattern was magnified in the early stage DAT groups. Performance variability appeared especially sensitive to DAT-related changes, as reliable differences between healthy OA and very mild DAT individuals emerged for multiple tap rates. These differences are proposed to result from breakdowns in attentional control that disrupt error-correction processes and the ability to resolve discrepancies between internally-generated temporal expectancies and the external temporal demands of the repetitive timing task. [ABSTRACT FROM AUTHOR]

Descriptive cross-sectional, quantitative study, aimed to identify the level of depression in a sample of informal caregivers of Alzheimer's patients, composed of 52 subjects. Consideration was given to the following inclusion criteria: primary informal caregiving, with at least 3 months in the care of the patient, with no financial compensation and taking care of non-institutionalized patients. The Depression Inventory (state / trait)IDER, was applied on the sample; The results of the test show a 46.2% in the scale of total state, and a 51.9% in euthymic state subscale, showing also a high incidence of depression. In full scale of trait, there is a total absence of 76.9%, but in the dysthymia subscale, the trait had an absence of 88.5%, therefore, there is no relevance in terms of the level of depression as a trait. [ABSTRACT FROM AUTHOR]

Post-mortem brain tissue was obtained from 28 patients with brain disorders, of which 15 had clinically diagnosed schizophrenia, 6 Alzheimer type dementia, 5 dementia with tangles and 2 cases of Down's syndrome. The controls were 22 cases from autopsies without brain disorders or with no known episodes of brain disorder. The tissues were stained for the detection of carbohydrate deposits in the hippocampal formation, using lectin, immunohistochemical and conventional staining methods. The staining revealed the existence of spherical deposits in the inner and middle molecular layers of the dentate gyrus in the hippocampal formation which contained fucose, galactose, N-acetyl galactosamine, N-acetyl glucosamine, sialic acid, mannose and chondroitin sulfate. The number of the deposits was higher in patients with brain disorder such as schizophrenia, Alzheimer type dementia, dementia with tangles or Down's syndrome, and in some aged individuals, in comparison to those in younger individuals. No deposits were detected in a few younger or aged individuals. Spherical deposits 3–10[emsp4 ]μm in diameter may be an immature form of the corpora amylacea, since they were similar in the histochemical characteristics with lectin, immunohistochemical and conventional staining methods. However, differing staining ability by hematoxylin, periodic acid Schiff's reagent and antibodies against the intracellular degraded proteins such as ubiquitin and tau-protein was observed. The antibodies against ubiquitin and tau-protein showed clear reactivity with the corpora amylacea and no reactivity with spherical deposits, indicating that the corpora amylacea has an intracellular origin and spherical deposits an extracellular matrix origin. The results obtained in this study indicate that not only neuronal degeneration but also unusual glycometabolism in neurons may disturb the neuronal function and cause brain disorders, and that spherical deposits may cause dysfunction of the neuronal network in the dentate gyrus of the hippocampus which is closely linked with recognition and memory functions. [ABSTRACT FROM AUTHOR]

Visuospatial memory was studied in patients suffering from senile dementia of the Alzheimer type (SDAT). They had been allocated into one of two groups depending on the severity of their disorder (mild or moderate), and a control group of healthy elderly subjects was included. Three different microcomputer-controlled tasks were used. The spatial span task was able to distinguish between the two SDAT groups. Both groups were impaired, relative to control, on spatial recognition. The deficit in spatial working memory was also equivalent in the mild and moderate groups and was accompanied by evidence of an intact strategic approach to the task. The normal positive relationship between spatial memory performance and strategy was in fact reversed in the SDAT groups, suggesting a pure spatial memory deficit. These results show that spatial memory processes are impaired in the early stages of SDAT and get worse as the disease progresses. The also suggest that the neuroanatomical foci of the deficits may be predominantly in posterior cortical regions (including hippocampus), rather than the frontal cortex. [ABSTRACT FROM AUTHOR]

We studied changes in the concentrations of serotonin (5-HT), kynurenine, and other indoleamines in the cerebrospinal fluid of patients with Alzheimer type dementia (ATD) and those with Binswanger type vascular dementia (VDBT), and changes in these indoleamine concentrations 2 weeks after administration of citalopram, a 5-HT uptake inhibitor. The concentrations of total 5-HT (p<0.005) and kynurenine (p<0.005) were significantly decreased in ATD patients in comparison to those of the controls. After citalopram administration, there was a remarkable increase in 5-HT concentration (249%, p<0.0001) and a significant decrease in 5-HIAA concentration (22%, p<0.02). In the VDBT patients, only 5-HT showed a significant decrease (p<0.005) in comparison to the control values. It also increased significantly (214%) after citalopram administration. The 5-HT/tryptophan and kynurenine/tryptophan ratios were not correlated for the controls, but did significantly for the ATD and VDBT patients; after citalopram treatment, the increase in 5-HT/tryptophan was correlated significantly with that of kynurenine/tryptophan for ATD, but not for VDBT. These results suggest that both the serotonin and kynurenine pathways are impaired in ATD; whereas, the serotonin pathway alone is in VDBT, and that these impairments are ameliorated by the administration of citalopram. [ABSTRACT FROM AUTHOR]

We determined the urate and xanthine concentrations in the cerebrospinal fluid (CSF) in patients with vascular dementia of the Binswanger type (VDBT), Alzheimer type dementia (ATD), and Parkinson's disease (PD). We found that the urate concentration was significantly increased in VDBT patients, but significantly decreased in ATD patients compared with controls. The ratio of the concentrations of uric acid (U) to xanthine (X) in the CSF (U/X) had a significant correlation with the ratio of the U to the urate concentration in serum (U) (U/U) in ATD and PD, whereas U/U increased independently of U/X in VDBT. We concluded that the significant increase in the urate concentration in VDBT is mainly due to an impairment of the blood-brain barrier (BBB), and its significant reduction in ATD may reflect impaired brain metabolism. [ABSTRACT FROM AUTHOR]