Effects of 12-month exercise intervention on physical and cognitive functions of nursing home residents requiring long-term care: a non-randomised pilot study.

AIMS: We performed a 12-month exercise intervention for 'nursing home for the elderly' residents requiring long-term care. We evaluated changes in their muscular strength, muscle mass, and cognitive function. METHODS: Thirty-seven nursing home residents (Mini-Mental State Examination (MMSE): 14.7 ± 7.0, Barthel Index: 44.2 ± 18.9) were enrolled. We divided the participants into the exercise intervention group (n = 19) and non-intervention group (n = 18) ensuring no significant difference in the participants' characteristics at baseline. For the exercise intervention group, exercise was performed for about 40 min twice a week for 12 months. Skeletal Mass Index and grip force were determined to evaluate muscle mass and muscle strength, respectively. MMSE, Trail Making Test (TMT) part A, and Geriatric Depression Scale 15 (GDS15) were used for cognitive function evaluation, with their changes investigated. RESULTS: After 12 months, the MMSE scores were significantly improved in the exercise intervention group compared with the non-intervention group (change from baseline to 12 months: Non-intervention: -1.0 ± 2.8, Intervention: 1.2 ± 3.0; P = 0.04). Moreover, the grip force of the dominant arm was significantly improved in the exercise intervention group compared with the non-intervention group (change from baseline to 12 months: Non-intervention: -1.3 ± 2.8 kg, Intervention: 1.4 ± 4.6 kg; P = 0.007). The prevalence of sarcopenia was significantly increased after 12 months compared with baseline in the non-intervention group (Non-intervention: 61.1% → 75.0%, Intervention: 77.8% → 71.4%; P < 0.02). There were no significant changes in GDS15, Barthel Index and TMT after 12 months in intervention and non-intervention groups. CONCLUSION: Exercise intervention may be effectively used for improving the physical and cognitive functions of nursing home residents requiring long-term care.

Diabetes-Related Dementia.

Type 2 diabetes mellitus (DM) has been shown to increase the risk for cognitive decline and dementia, such as in Alzheimer disease (AD) and vascular dementia (VaD). Additionally, there may be a dementia subgroup associated with specific DM-related metabolic abnormalities rather than with AD pathology or cerebrovascular diseases. This type of dementia, not showing hypoperfusion in the parietotemporal lobe on SPECT or cerebrovascular lesions on MRI, was characterized by old age, high hemoglobin A1c level, long duration of diabetes, high frequency of insulin therapy, low frequency of apolipoprotein E4 carrier, less-severe medial temporal lobe atrophy, impaired attention and executive function, less-impaired word recall, and slow progression of cognitive impairment and might be referred to as "diabetes-related dementia" (DrD). 11C-Pittsburgh compound-B PET shows often negative or equivocal amyloid accumulation in the brain, indicating different from AD pathology. In addition to insulin resistance, elevated inflammatory cytokines, oxidative stress, and advanced glycation end products were associated with cognitive impairment in this type of dementia. Glycemic controls can improve some domains of cognitive function, such as attention and executive functions, in subjects with DrD. Frequencies of frailty and sarcopenia/dynapenia are significantly higher in DrD than in AD, indicating that geriatric interventions are necessary to improve clinical outcomes for patients with DrD. DrD can be considered as a controllable or modifiable dementia. The identification of DrD, as distinct from other types of dementia, may be necessary for considering appropriate therapy and prevention in clinical practice.

[A suspicious case of coagulation disorder caused by vitamin K deficiency associated with fasting and antibiotics].

Coagulation disorders due to some antibiotics containing N-methyl-thiotetrazole group and vitamin K (VK) deficiency by microbial substitution in the intestinal flora can occur. We report a case of coagulation disorder under fasting with conventional antibiotics which are not containing N-methyl-thiotetrazole. A 91-year-old man was hospitalized for diagnosis of acute exacerbation of chronic heart failure because of bronchitis. He received treatment of fasting, fluid replacement, antibiotics, and a diuretic. On the 3rd day, left frontal lobe bleeding occurred. We performed conservative treatment with central venous nutrition not containing VK. Administration of antibiotics was completed after 14 days. On the 28th day, catheter-related bloodstream infection developed. Vancomycin and cefazolin were administered. The prothrombin time-international standard ratio (PT-INR) on the 1st day of administration was 1.2; however, it gradually increased to 7.4 on the 7th day of administration. Menatetrenone and fresh frozen plasma were administered as symptomatic treatment. Vancomycin was discontinued because a blood culture was positive for methicillin- susceptible coagulase negative Staphylococcus (CNS). After the 8th day of administration, the PT-INR improved to 1.1, but it increased to 1.9 on the 14th day. VK deficiency due to the antimicrobial drug was predicted. Therefore, VK and fresh frozen plasma were re-administered to improve the PT-INR. The PT-INR returned to normal after administration of cefazolin was terminated. Antimicrobial administration in the long term under the fasting condition can suppress endogenous production of VK by changing intestinal bacteria. And it has been reported that cefazolin which containing Methyl-thiadiazole thiol inhibits VK metabolic cycle and causes coagulation disorder. These reasons seems to a coagulation disorder. Therefore, physicians should monitor the coagulation system in this situation.

123I-MIBG myocardial scintigraphy for the diagnosis of DLB: a multicentre 3-year follow-up study.

BACKGROUND AND PURPOSE: We previously reported the usefulness of iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy for differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) in a cross-sectional multicentre study. The aim of this study was, by using reassessed diagnosis after 3-year follow-up, to evaluate the diagnostic accuracy of 123I-MIBG scintigraphy in differentiation of probable DLB from probable AD. METHODS: We undertook 3-year follow-up of 133 patients with probable or possible DLB or probable AD who had undergone 123I-MIBG myocardial scintigraphy at baseline. An independent consensus panel made final diagnosis at 3-year follow-up. Based on the final diagnosis, we re-evaluated the diagnostic accuracy of 123I-MIBG scintigraphy performed at baseline. RESULTS: Sixty-five patients completed 3-year follow-up assessment. The final diagnoses were probable DLB (n=30), possible DLB (n=3) and probably AD (n=31), and depression (n=1). With a receiver operating characteristic curve analysis of heart-to-mediastinum (H/M) ratios for differentiating probable DLB from probable AD, the sensitivity/specificity were 0.77/0.94 for early images using 2.51 as the threshold of early H/M ratio, and 0.77/0.97 for delayed images using 2.20 as the threshold of delayed H/M ratio. Five of six patients who were diagnosed with possible DLB at baseline and with probable DLB at follow-up had low H/M ratio at baseline. CONCLUSIONS: Our follow-up study confirmed high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy at baseline and the clinical diagnosis of probable DLB at 3-year follow-up. Its diagnostic usefulness in early stage of DLB was suggested. TRIAL REGISTRATION NUMBER: UMIN00003419.

Caregivers' education decreases depression symptoms and burden in caregivers of patients with dementia.

OBJECTIVE: To determine whether providing education to caregivers of patients with dementia decreases their depression symptoms and burden. METHODS: Eighty-three outpatients with dementia being treated at the Memory Clinic of Tokyo Medical University Hospital and their caregivers were enrolled. Forty-seven caregivers were enrolled in the caregivers' education (EDU) group and 36 were enrolled in the control (CTL) group. Caregivers were assessed for depression, burden, and quality of life (QoL). Patients were assessed for cognition, psychological symptoms, and QoL. Assessments were carried out at baseline and at 3 months (3M). Caregivers in the EDU group received lectures on symptoms and progression of dementia, management of symptoms, use of social resources etc. RESULTS: At 3M, prevalence of depression symptoms in the EDU group significantly decreased from 36% to 17%, whereas it significantly increased from 22% to 50% in the CTL group. Depression and burden were significantly improved at 3M in the EDU group, whereas they significantly worsened in the CTL group. Psychological symptoms showed a lower tendency at 3M for the EDU group. No significant changes in QoL of caregivers and patients were found in either group. CONCLUSIONS: Providing education to caregivers of patients with dementia improves their depression symptoms and sense of burden, and tends to improve the behaviour and psychological symptoms of dementia in the patients. Providing education to caregivers of dementia patients may hence result in beneficial effects for both the patients and their caregivers, and should be widely used in dementia care.

Utility of the combination of DAT SPECT and MIBG myocardial scintigraphy in differentiating dementia with Lewy bodies from Alzheimer's disease.

PURPOSE: (123)I-2ß-Carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT SPECT) and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy can be used to assist in the diagnosis of patients with dementia with Lewy bodies (DLB). We compared the diagnostic value of these two methods in differentiating DLB from Alzheimer's disease (AD). Furthermore, we evaluated whether a combination of DAT SPECT and MIBG myocardial scintigraphy would provide a more useful means of differentiating between DLB and AD. METHODS: Patients with AD (n = 57) and patients with DLB (n = 76) who underwent both DAT SPECT and MIBG myocardial scintigraphy were enrolled. The sensitivity, specificity, and accuracy of both methods as well as their combination for differentiating DLB from AD were calculated. Moreover, we examined whether symptoms of the patients with DLB were associated with the patterns of the abnormalities displayed on DAT SPECT and MIBG myocardial scintigraphy. RESULTS: The sensitivity and specificity of differentiating DLB from AD were 72.4 and 94.4 % by the heart to mediastinum ratio of MIBG uptake, 88.2 and 88.9 % by the specific binding ratio on DAT SPECT, and 96.1 and 90.7 % by their combination, respectively. The combined use of DAT SPECT and MIBG myocardial scintigraphy enabled more accurate differentiation between DLB and AD compared with either DAT SPECT or MIBG myocardial scintigraphy alone. There was a significantly higher frequency of parkinsonism in the abnormal DAT SPECT group than the normal DAT SPECT group. On the other hand, there was a higher frequency of the appearance of rapid eye movement (REM) sleep behavior disorder in the abnormal MIBG uptake group than the normal MIBG uptake group. CONCLUSION: These results suggested that using a combination of these scintigraphic methods is a useful and practical approach to differentiate DLB from AD.

[Diabetes-related dementia].

Type 2 diabetes mellitus (DM) has been shown to increase the risk of cognitive decline and dementia, such as Alzheimer's disease (AD) and vascular dementia. Among subjects with dementia and DM, there is a dementia subgroup with characteristics predominantly associated with DM-related metabolic abnormalities rather than AD or vascular pathology. The subgroup was characterized by old age, high hemoglobin A1c level, long duration of diabetes, high frequency of insulin therapy, low frequency of apolipoprotein E4 carrier status, less severe medial temporal lobe atrophy, impaired attention but less impaired word recall, and slower progression of cognitive impairment, referred to as "diabetes-related dementia". The identification of diabetes-related dementia may be necessary for considering an appropriate therapy and prevention in clinical practice.

[Defining and disease-modifying therapy for the preclinical stages of Alzheimer's disease].

The pathophysiological process of Alzheimer's disease (AD) is thought to begin more than twenty years before the diagnosis of AD dementia. Recent studies provided the biomarker of AD pathological changes. Biomarkers of brain Aß amyloidosis include reduction in cerebrospinal fluid (CSF) Aß42 and increased amyloid tracer retention on positron emission tomography(PET) imaging. Elevated CSF tau is thought to be a biomarker of neuronal injury. The Natinal Institute on Aging and the Alzheimer's Association proposed AD dementia, mild cognitive impairment due to AD, the preclinical stage of AD. These recommendation for the biomarker of AD are intended for research purposes at this time. Some disease-modifying therapies may be effective for the preclinical stage of AD.

[Mild cognitive impairment].

Mild cognitive impairment(MCI) is considered to be a transition state between normal cognition and dementia. The subtypes of MCI are highly heterogeneous in terms of etiology, presentation, and prognosis. Patients with the amnestic subtype of MCI are at a high risk of progression to Alzheimer disease (AD); this subtype may represent the prodromal stage of AD. Moreover, patients with MCI who are not aware of their memory deficits and in whom practice effects are not observed exhibit parietotemporal hypoperfusion on single photon emission CT, indicating that these findings are predictors of progression to AD. In this review, I have discussed the most current aspects related to the concept and clinical presentation of MCI.

[Cognitive Function and Calcium. Vitamin D and calcium for the prevention of falls and fractures in patients with dementia].

The prevalence of dementia and fractures has been increasing with age. There is strong evidence that dementia or cognitive impairment in older people has an established fall risk factor. Subjects with dementia have a doubled to threefold risk of falls. In addition to motor impairments (impaired gait, reduced muscular strength and impaired balance) , executive functional impairment is also associated with an increased risk of falls. Falls are more likely found in subjects with dementia with Lewy bodies and vascular dementia and those who had advanced dementia. Patients with AD are at higher risk for fractures and have a lower bone mineral density than healthy controls. Vitamin D decreases vertebral fractures, and moreover, appears to reduce the risk of falls in older subjects. A recent meta-analysis showed that vitamin D concentrations are associated with poor cognitive function and a higher risk of AD. However, treatment with vitamin D alone shows no significant effect on cognition in patients with AD.

[Lipid abnormality].

Vascular dementia is caused by stroke, so primary and secondary prevention for stroke is extremely important. Effects of statins on stroke prevention in patients are reported from recent randomized controlled trials. Hypercholesterolemia in midlife are related to an increased risk of Alzheimer's disease (AD) in later life. During the past decade, effects of statins for patients with AD are controversial in many subsequent original studies. Accordingly, it remains unknown whether statin therapy have a preventive effect on cognitive decline in patients with AD. As a possible mechanism, hypercholesterolemia may be associated with the progression of AD pathology. As another possible mechanism hypercholesterolemia may be associated with hypoperfusion through the progression of atherosclerosis.

Factors and brain imaging features associated with cognition in oldest-old patients with Alzheimer-type dementia.

BACKGROUND: The underlying pathophysiology of cognitive dysfunction in oldest-old patients with Alzheimer-type dementia (AD) has not been clarified to date. We aimed to determine the factors and brain imaging features associated with cognition in oldest-old patients with AD. METHODS: We enrolled 456 consecutive outpatients with probable AD (145 men and 311 women, age range: 51-95 years). Demographic factors, such as education level, disease duration at initial visit, body mass index, comorbidities, frailty, and leisure activity, and brain imaging features, including severity of medial temporal lobe (MTL) atrophy, white matter lesions and infarcts, and frequency of posterior cerebral hypoperfusion were compared among pre-old (≤ 74 years), old (75 to 84 years), and oldest-old (≥ 85 years) subgroups. RESULTS: The oldest-old subgroup showed significantly longer disease duration, lower education level, more severe frailty, less leisure activity, worse cognitive impairment, a tendency of slower progression of cognitive decline, greater MTL atrophy, more severe white matter hyperintensities and infarcts, and lower frequency of posterior hypoperfusion than the younger age subgroups. Regarding the brain imaging subtypes, there were significantly more patients with the limbic-predominant subtype and fewer patients with the hippocampal-sparing subtype in the oldest-old AD group than the pre-old AD group. CONCLUSIONS: Oldest-old patients with AD show different factors and brain imaging features associated with cognition from pre-old and old patients. Our results are expected to provide useful information towards understanding the pathophysiology of oldest-old patients with AD, and for determining their clinical diagnosis and appropriate management methods.

Subgroups of Alzheimer's disease associated with diabetes mellitus based on brain imaging.

BACKGROUND/AIMS: We attempted to define possible subgroups of Alzheimer's disease (AD) associated with diabetes mellitus (DM) based on brain imaging. METHODS: We classified 175 patients with clinically diagnosed AD and type 2 DM into 4 subgroups on the basis of the presence or absence of cerebrovascular disease (CVD) on MRI (CVD or no CVD) and posterior cerebral hypoperfusion on SPECT (AD pattern or no AD pattern). Differences in the clinical characteristics among the subgroups were examined. RESULTS: The subgroup showing neither a CVD pattern nor an AD pattern had significantly older age, higher hemoglobin A1c level, longer duration of diabetes, higher frequency of insulin therapy, lower frequency of apolipoprotein E4 carriers, less severe medial temporal lobe atrophy, more impaired attention, less impaired word recall, and slower progression of cognitive impairment than the subgroup showing an AD pattern. We found no characteristic features of other subgroups. CONCLUSION: The clinical features of subjects with AD associated with DM may differ depending on brain imaging patterns. Among them, there may be a dementia subgroup with characteristics predominantly associated with DM-related metabolic abnormalities.

[Leg edema detected on comprehensive geriatric assessment for elderly outpatients and its associated risk factors].

AIM: Leg edema, observed on comprehensive geriatric assessment (CGA) of 142 elderly outpatients with a variety of chronic diseases, was studied clinically to clarify its incidence and its associated risk factors. METHODS: The severity of pitting edema was assessed at 3 points, namely, the pretibial edge, medial malleolus, and the dorsum of the foot. On palpation, edema was graded as 0 to 3 for each point on one leg, the sum of which was used as the edema score. According to the edema score, subjects were divided into 3 groups; the moderate to severe (MS) group, the slight to mild (SM) group, and the group without pitting edema. The MS group was defined as having an edema score of 4 or more or edema of grade 2 or more, while the SM group was defined as having an edema score of 2 to 3 points without edema of grade 2 or more. The status of underlying disease, vascular risks, varicose veins, medications, daily activity, nutrition, total protein (TP), albumin, brain natriuretic peptide (BNP), and the estimated glomerular filtration rate (eGFR) were compared among the 3 groups. RESULTS: There were 36 subjects in the MS group and 19 subjects in the SM group. Diabetes, atrial fibrillation, varicose veins, and polypharmacy were more frequent in the MS group than in the control group. Sedentary life style, house-bound, and gait trouble were significantly more frequent in the MS and SM groups. There were no significant differences in the scores of the Mini-Nutritional Assessment Short Form among the groups, although both the body weight and calf circumference in the MS group were significantly greater than those in the group without pitting edema. Low serum TP, albumin and eGFR were seen in the MS group as well as high BNP levels. Multiple regression analysis revealed diabetes, varicose veins, sedentarism, and hypoalbuminemia as risk factors associated with leg edema (R(2)=0.365, p<0.0001). CONCLUSION: Leg edema was frequent in the elderly outpatients and was associated strongly with diabetes, varicose veins, sedentarism, and hypoalbuminemia. These findings suggest that advising against a sedentary life style could help the resolution of edema, and also indicates the clinical usefulness of CGA. Furthermore, leg edema should be seriously considered along with nutritional assessment because edema could influence various anthropometric parameters.

[Age-related changes of sensory system].

Pathological processes usually superimpose on physiological aging even in the sensory system including visual, hearing, olfactory, taste and somatosensory functions. Representative changes of age-related changes are presbyopia, cataracts, and presbyacusis. Reduced sense of smell is seen in normal aging, but the prominent reduction detected by the odor stick identification test is noticed especially in early stage of Alzheimer or Parkinson disease. Reduced sense of taste is well-known especially in salty sense, while the changes of sweet, bitter, and sour tastes are different among individuals. Finally, deep sensation of vibration and proprioception is decreased with age as well as superficial sensation (touch, temperature, pain). As a result, impaired sensory system could induce deterioration of the activities of daily living and quality of life in the elderly.

Longitudinal patterns of Alzheimer's disease subtypes: A follow-up magnetic resonance imaging and single-photon emission computed tomography study.

AIM: Alzheimer's disease (AD) is a biologically heterogenous disease. In a previous study, we classified 245 patients with probable AD into the typical AD (TAD), limbic-predominant (LP), hippocampal-sparing (HS) and minimal-change (MC) subtypes based on their medial temporal lobe atrophy on magnetic resonance imaging and posterior hypoperfusion on single-photon emission computed tomography, and described differences in clinical features among the patients with different AD subtypes. This study aimed to clarify the longitudinal patterns of changes in patients with the various AD subtypes by follow-up brain imaging analyses. METHODS: Follow-up magnetic resonance imaging or single-photon emission computed tomography data obtained 12-48 months after the first brain imaging were investigated in 79 patients with probable AD, comprising 25 of the TAD subtype, 19 of the LP subtype, 17 of the HS subtype and 18 of the MC subtype. RESULTS: All patients of the TAD subtype remained as the same subtype at follow up. Approximately 37% of patients of the LP subtype and 29% of patients of the HS subtype progressed to the TAD subtype, and 17%, 33% and 6% of the MC subtype progressed to the TAD, LP and HS subtypes, respectively. The group of patients showing subtype progression was associated only with a longer follow-up duration. CONCLUSIONS: There might be different progression patterns and progression rates of changes among the atypical AD subtypes. Further longitudinal brain imaging studies might provide information regarding the pathophysiological association between the various AD subtypes, and might be helpful for determining appropriate therapies and management methods. Geriatr Gerontol Int 2023; 23: 919-924.