Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer's disease, frontotemporal dementia and vascular dementia

OBJECTIVES: Alzheimer's disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) are the three most common causes of young onset dementias. Most neuroimaging studies of these disorders have involved comparisons with normal controls. The aims of this study were to examine the clinical diagnostic value of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) (in combination and in isolation) in the differentiation of one form of dementia from another from amongst a group of AD, FTD and VaD. METHODS: T1 weighted MRI images and 99mTc-HMPAO SPECT images were obtained from consecutive patients with FTD (n=21), AD (n=23) and VaD (n=20) and rated visually by experienced neuroradiologists and nuclear medicine physicians. RESULTS: Asymmetrical atrophy was seen only in FTD. Frontotemporal dementia patients were the most atrophic whereas severe atrophy was rarely observed in VaD. Severe frontal atrophy (unilaterally or bilaterally) and/or asymmetrical atrophy on MRI is highly diagnostic (sensitivity 0.71, specificity 0.93, LR 10.24) of FTD from within a group of FTD and non-FTD (AD, VaD) patients. Mild or severe parietal atrophy with severe reduction in parietal regional cerebral blood flow on SPECT is diagnostic (sensitivity 0.71, specificity 0.76, LR 3.02) of AD from within a group of AD and non-AD (VaD, FTD) patients. CONCLUSION: Anatomical (MRI) and functional (SPECT) imaging provide different information and a combination of these modalities improves diagnostic specificity.     

Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer's disease, vascular dementia and frontotemporal dementia

Noncognitive behavioral and psychiatric disturbances are common in dementia and help in the clinical differentiation of the various subtypes. We studied the frequency of neuropsychiatric disturbances, their relationship to dementia severity and compared these disturbances in Alzheimer's disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) using the 12-item Neuropsychiatric Inventory (NPI). A total of 98 patients (AD-44, VaD-31, FTD-23) were evaluated. All subjects were community dwelling at the time of evaluation. The three groups were comparable on global dementia severity and functional ability. All patients had clinically significant scores on the NPI with apathy, irritability and agitation being very common (>90% of patients). AD and VaD patients in Clinical Dementia Rating (CDR) stage 2 had significantly higher scores on the total NPI, agitation and disinhibition subscales compared to those in CDR stage 1. Mean scores in the domains of aberrant motor behavior, disinhibition and appetite/eating behavior differentiated FTD from AD and VaD. Neuropsychiatric disturbances in dementia appear to be universal with agitation, disinhibition and irritability being more frequent in the later stages. In this cohort disinhibition, aberrant motor behavior and appetite/eating disturbances could reliably differentiate AD and VaD from FTD. There were no significant differences between the neuropsychiatric profiles of AD and VaD.     

Criminal Behaviour After Diagnosis of a Neurocognitive Disorder: A Nationwide Finnish Register Study

ObjectiveTo explore criminal behavior of individuals with Alzheimer's disease (AD), frontotemporal dementia (FTD), or Lewy body dementias (LBD) after the diagnosis.DesignNationwide register study.SettingInformation on diagnoses and criminality was received from Finnish registers. Crime types and incidences were compared between disorders and the general population.ParticipantsAll Finnish individuals diagnosed with AD, LBD, or FTD (n = 92 189) during 1998–2015.MeasurementsTypes of crimes and incidences, the standardized criminality ratio (SCR, number of actual crimes per number of expected crimes), numbers of observed cases, and person-years at risk counted in 5-year age groups and for both sexes and yearly.ResultsAmong men, at least one crime was committed by 2.8% of AD, 7.2% of FTD, and 4.8% of LBD patients. Among women, the corresponding figures were 0.4%, 2.0%, and 2.1%. The most frequent type of crime was traffic offence, followed by property crime. After age adjustment, the relative number of crimes between groups did not differ, except that men with FTD and LBD committed more crimes than those with AD. The SCR (95% CI) among men were 0.40 (0.38–0.42) in AD, 0.45 (0.33–0.60) in FTD, and 0.52 (0.48–0.56) in LBD. Among women, these were 0.34 (0.30–0.38), 0.68 (0.39–1.09), and 0.59 (0.51–0.68).ConclusionsThe diagnosis of a neurocognitive disorder does not increase criminal behavior, but rather reduces it by up to 50%. Differences in crime activity are present between different neurocognitive disorders and between the sexes.     

Aging and the occurrence of dementia: findings from a population-based cohort with a large sample of nonagenarians.

CONTEXT: In spite of numerous studies on the occurrence of dementia, many questions remain, such as the relation between age, aging, and dementing disorders. This question is relevant both for understanding the pathogenetic mechanism of the dementias and for the public health prospective because of the increasing number of 85-year-old or older persons in our population. OBJECTIVE: To estimate the occurrence of dementia in the very old, including nonagenarians, in relation to age, gender, and different dementia types. DESIGN: An epidemiological survey where all participants were clinically examined by physicians, assessed by psychologists, and interviewed by nurses. The Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for dementia were followed. A category of "questionable dementia" was added when all criteria were not fulfilled. A double diagnostic procedure was used for all subjects. SETTING: Community-based population, including all inhabitants of 2 areas in central Stockholm, Sweden (N = 1848). PARTICIPANTS: Of the 1848 subjects in the study population, 168 (9.1%) had died and 56 (3%) moved before examination. Of the remaining subjects, 1424 (87.7%) were examined, and the refusal rate was 12.3%. MAIN OUTCOME MEASURES: Age- and gender-specific prevalence figures, and gender- and education-adjusted odds ratios were used. RESULTS: At the end of the diagnostic procedure, 358 clinically definite cases of dementia and 101 questionable cases of dementia were identified. Alzheimer disease (AD) contributed to 76.5%, and vascular dementia (VaD) to 17.9%. The prevalence of dementia increases from 13% in the 77- to 84-year-old subjects to 48% among persons 95 years and older (from 18% to 61% when questionable cases were included). The odds ratio for subjects 90 to 94 years and 95 years and older in comparison with 77- to 84-year-old subjects was 3.7 (95% confidence interval [CI], 2.7-5.1) and 6.5 (95% CI, 3.9-10.8) for dementia, 4.8 (95% CI, 3.3-7.0) and 8.0 (95% CI, 4.6-14.0) for persons with AD, 2.3 (95% CI, 1.3-4.2) and 4.6 (95% CI, 1.9-11.2) for VaD, respectively. CONCLUSIONS: Dementia prevalence continues to increase even in the most advanced ages. This increase is especially evident among women and is more clear for AD. We believe that our prevalence data reflect the differential distribution of dementia risk.     

Diagnostic value of high signal abnormalities on T2 weighted MRI in the differentiation of Alzheimer's, frontotemporal and vascular dementias

OBJECTIVE: The occurrence of high signal abnormalities on T2 weighted images is strongly age related. The diagnostic value of these changes in a younger population with dementia is not currently known. We studied the potential of high signal changes on magnetic resonance imaging (MRI) in differentiating Alzheimer's disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) in younger patients. METHODS: High signal abnormalities were rated, using a previously validated scale, from hard copies of T2 weighted axial images of 102 patients with AD (n=49), VaD (n=31), FTD (n=22) (mean ages 63-65 years). RESULTS: High signal abnormalities were widespread across AD, VaD and FTD. Although they were most frequent and most severe in the VaD group only lacunes and grade III deep white matter hyperintensities (DWMH) were specific for these patients. CONCLUSIONS: High signal changes on T2 weighted images on MRI are common across degenerative (AD and FTD) and vascular dementias. Although lacunes and grade III DWMH are specific for VaD, the low sensitivities (sensitivities: for lacunes, 0.32; for grade III DWMH, 0.16) limit their use as diagnostic markers for VaD. High signal changes on MRI should be interpreted with caution in dementias. Their presence, even in younger patients, should not deter one from diagnosing AD or FTD.     

Epidemiology of non-AD dementias

Dementia is a common neurodegenerative disorder that affects about 10% of the population over 65 years of age. A distinction can be made between primary degenerative dementias and dementia secondary to other diseases. This review focuses on the primary non-Alzheimer's disease (AD) dementias: vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). VaD is after AD most frequent subtype of dementia with a prevalence of about 1%, ranging from 0 to 10% mainly depending on the age group investigated and the criteria used. Its incidence rate is between 1.5 and 4.1 per 1000 person-years, with no clear difference between men and women and with possibly a higher incidence in East Asia compared to Canada and Europe. Most of the VaD cases are sporadic although there are some rare familial forms of VaD as cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy and familial cerebral amyloid angiopathy. Important risk factors for sporadic VaD are cerebrovascular pathology (brain infarction, white matter lesions and brain atrophy), midlife hypertension, and diabetes leading to increasing risk ratios. A protective effect is often found for education and moderate use of alcohol. The association between VaD and amyloid β, cholesterol, and statin use remains unclear yet. DLB and FTD are less frequent forms of dementia with prevalence rates of, respectively, 0.1–0.6 and 0.002–0.015%. FTD affects people in their middle age, accounting for up to 10–20% of the presenile dementia cases. About 14% of the FTD cases are caused by an autosomal dominant tau-mutation. However, since the prevalence of sporadic FTD is relatively low, population-based epidemiological studies are hard to perform and no non-genetic risk factors are known yet. DLB is a relative common form of dementia in old age accounting for 15–20% of cases in hospital autopsy case-series. The only known possible risk factor for DLB is the presence of an apolipoprotein E 4 allele.     

Assessment of free and cued recall in Alzheimer’s disease and vascular and frontotemporal dementia with 24-item Grober and Buschke test

Alzheimer’s disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) are the most common forms of dementia. It is well known that memory deficits in AD are different from those in VaD and FTD, especially with respect to cued recall. The aim of this clinical study was to compare the memory performance in 15 AD, 10 VaD and 9 FTD patients and 20 normal controls by means of a 24-item Grober-Buschke test [8]. The patients’ groups were comparable in terms of severity of dementia. We considered free and total recall (free plus cued) both in immediate and delayed recall and computed an Index of Sensitivity to Cueing (ISC) [8] for immediate and delayed trials. We assessed whether cued recall predicted the subsequent free recall across our patients’ groups. We found that AD patients recalled fewer items from the beginning and were less sensitive to cueing supporting the hypothesis that memory disorders in AD depend on encoding and storage deficit. In immediate recall VaD and FTD showed a similar memory performance and a stronger sensitivity to cueing than AD, suggesting that memory disorders in these patients are due to a difficulty in spontaneously implementing efficient retrieval strategies. However, we found a lower ISC in the delayed recall compared to the immediate trials in VaD than FTD due to a higher forgetting in VaD.     

Qualitative aspects of learning, recall, and recognition in dementia

Objective:

To determine whether learning and serial position effect (SPE) differs qualitatively and quantitatively among different types of dementia and between dementia patients and controls; we also wished to find out whether interference affects it.

Materials and Methods:

We administered the Malayalam version of the Rey Auditory Verbal Learning Test (RAVLT) to 30 cognitively unimpaired controls and 80 dementia patients [30 with Alzheimer''s disease (AD), 30 with vascular dementia (VaD), and 20 with frontotemporal dementia (FTD)] with mild severity on the Clinical Dementia Rating Scale.

Results:

All groups were comparable on education and age, except the FTD group, who were younger. Qualitatively, the learning pattern and SPE (with primacy and recency being superior to intermediate) was retained in the AD, VaD, and control groups. On SPE in free recall, recency was superior to intermediate in the FTD group (P < 0.01 using Bonferroni correction). On recognition, the AD and VaD groups had more misses (P < 0.01), while the FTD group had more false positives (P < 0.01).

Conclusion:

Quantitative learning is affected by dementia. The pattern of qualitative learning remains unaltered in dementia in the early stages.     

Cross-cultural comparison of mild cognitive impairment between China and USA

Individuals with mild cognitive impairment (MCI) are at increased risk for dementia of Alzheimer's type (DAT), vascular dementia (VaD), Lewy Body (LBD) and Fronto-temporal dementias (FTD). Risk factors and conversion rates of MCI to dementia have not been thoroughly investigated in developing countries. Chinese and English versions of Mini-Mental State Examination were administered serially among well-matched subjects from two clinics located in Xi'an, China and Houston, USA. Subtle cognitive impairments were weighed according to MCI criteria as defined previously. Subjects with MCI were followed for an additional 3 years after their identification. Diagnoses of VaD and DAT were made according to established criteria. During screening period, 73 American and 65 Chinese individuals were identified with MCI. After 3 years of MCI follow-up, of the 73 American MCI subjects, 35 (47.9%) developed DAT and 15 (20.5%) developed VaD. Of the 65 Chinese MCI subjects, 12 (18.5%) developed DAT and 19 (29.2%) developed VaD. According to Kaplan-Meier analysis, Chinese MCI subjects, despite their lower educational level, are 1.7 times less likely to progress to DAT and 2.3 times more likely to progress to VaD than American subjects within 3 years of MCI being identified (p<0.01). Data suggest that progression rates of MCI vary considerably among subjects from two countries. American MCI subjects are more prone to DAT, while Chinese subjects are more prone to VaD. Differences in genetic factors, cultures, educational levels, and preventive treatments of vascular risk factors are proposed as responsible for this uneven geographic distribution for different types of dementia.     

Frontotemporal degenerative dementias

Frontotemporal dementia (FTD) is a clinical term now used for a group of dementing neurodegenerative disorders marked clinically by general predominance of symptoms referable to the frontal lobes. Symptoms may include changes in language ability with expressive or receptive aphasia, and changes in personality, including disinhibited, obsessive, hyperoral, hypersexual, repetitive, and perseverative behaviors. Memory is often affected, but is usually not a primary symptom. Characteristically, analytic, navigational, and other visuospatial abilities may be quite preserved. The clinical symptomatology of FTD contrasts with the general predominance of temporal and parietal symptoms in the most common neurodegenerative disorder, Alzheimer's disease (AD). FTD symptoms also differ from those seen with the second most common neurodegenerative disorder, Lewy Body Dementia (LBD), which while having substantial clinical and pathological overlap with AD, often shows additional clinical visuospatial (occipital) and parkinsonian symptomatology. FTD likely constitutes the third most-common cause of degenerative dementia. Clinical overlap can sometimes make it difficult to distinguish individual cases from AD. Genetic studies have shown that FTD, like AD, occurs in both familial and nonfamilial types, and a proportion of FTD cases arise from autosomal dominant genetic disorders due to mutations in the tau gene. Some recent formulations include in the family of frontal degenerative disorders other dementias with frontal symptomatology such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Lending support to such a grouping, neuropathological studies show a group of histologies, sometimes including PSP and CBD, to be the substrates for clinical FTD.     

Prospective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects

OBJECTIVE: The authors conducted a prospective study of neurodegenerative and vascular dementia in Belgium. Strict diagnostic inclusion criteria were used to include well defined patients and controls. The results of apolipoprotein E (APOE) genotype effect on risk and clinical characteristics are presented. METHODS: APOE genotyping was performed in patients with probable Alzheimer's disease (AD) (n=504), frontotemporal dementia (FTD) (n=47), vascular dementia (VaD) (n=152), mixed dementia (n=132), mild cognitive impairment (MCI) (n=44), Parkinson's disease (PD) (n=30), dementia with Lewy bodies (DLB) (n=17), and multisystem atrophy (MSA)/progressive supranuclear palsy (PSP) (n=12). RESULTS: The APOE allele frequencies of this Belgian control population (epsilon 2: 6.9%; epsilon 3: 76.2%; epsilon 4: 16.9%) did not differ from those reported for other white populations. AD, MCI, and mixed dementia patients had higher APOE epsilon 4 (32.9%, 38.6%, and 28.4% respectively) and lower APOE epsilon 3 (62.2%, 53.4%, and 66.3%) frequencies compared with controls, whereas only AD and mixed dementia patients had lower APOE epsilon 2 frequencies (4.9% and 5.3%). Apart from a borderline significant different distribution of APOE allele frequencies in VaD patients compared with controls, no other differences were detected. The influence of APOE epsilon 4 on clinical features of dementia was limited to lower age at onset in AD patients and a less pronounced negative correlation between age at onset and number of epsilon 4 alleles in MCI and mixed dementia patients. CONCLUSIONS: This study confirmed the risk association between APOE epsilon 4 and AD. The observation that APOE epsilon 4 is associated with mixed dementia reflected the role of AD in the aetiopathogenesis of this condition. Although MCI is an aetiologically heterogeneous syndrome, the increased APOE epsilon 4 frequencies indicated that a large proportion of the MCI patients included in the study might be predisposed to develop AD.     

Apolipoprotein E epsilon 4 in an autopsy series of various dementing disorders

Apolipoprotein E (APOE) allele epsilon 4 is a risk factor for Alzheimer's disease (AD) and has also been associated with impaired recovery from brain injury. Previous studies on APOE epsilon 4 in dementing disorders other than AD have been rather conflicting, in particular concerning frontotemporal dementia (FTD) and vascular dementia (VD). In the present study we determined APOE genotype in an autopsy series of demented subjects and non-demented controls from the Netherlands Brain Bank. We attempted to create as clear-cut diagnostic groups as possible and paid close attention to AD-type histopathological changes in all cases. In comparison with the APOE epsilon 4 allele frequency in controls (0.12; n=163 subjects), the APOE epsilon 4 allele frequency was significantly increased in AD (0.42; n=320, p<0.0001), as well as in AD with Lewy bodies (0.43; n=41, p<0.0001) and in demented subjects with no other neuropathological findings than AD-histopathology insufficient for a diagnosis of AD (0.29; n=41, p<0.001). However, the APOE epsilon 4 allele frequency was not significantly increased in FTD (0.18; n=49), VD (0.10; n=20) or in Lewy body disease without concomitant AD changes (0.13; n=12). As concerns dementing disorders, our results suggest that APOE epsilon 4 is selectively associated with the presence of AD-type histopathology.     

Frequency of early and late-onset dementias in a Japanese memory disorders clinic

The aim of this study was to compare the diagnostic profiles of patients with early (age<65 years) and late (age>or=65 years) onset of dementia in a memory disorders clinic in Japan. A total of 512 consecutive memory clinic patients were evaluated using clinical information and results of examinations. Diagnosis of dementia was made according to DSM-III-R, and that of subtypes according to standard diagnostic criteria. A total of 464 patients met the criteria for dementia. Amongst late-onset patients (n=430), Alzheimer's disease (AD) (48.1%) was the most frequent cause of dementia, followed by AD with cerebrovascular disease (CVD) (31.4%), vascular dementia (VaD) (9.1%), dementia with Lewy bodies (DLB) (3.7%), frontotemporal lobar degeneration (FTLD) (1.6%), and others (5.8%). On the contrary, amongst early onset patients (n=34), the most common dementia diagnosis was AD (38.2%), followed by VaD (23.5%), FTLD (14.7%), AD with CVD (5.9%), DLB (2.9%), and others (17.6%). FTLD and VaD were significantly more common in the early onset group. All patients, but one, with DLB and Parkinson's disease dementia were late-onset. The relative frequencies of AD, VaD, and DLB in our series are consistent with epidemiologic findings in several Western countries; however, the frequency of FTLD is not consistent with the previous findings presenting high frequency in late-onset patients in some Western countries.     

18FDG PET in vascular dementia: differentiation from Alzheimer's disease using voxel-based multivariate analysis.

The brain metabolic pattern of vascular dementia (VaD) remains poorly characterized. Univariate voxel-based analysis ignores the functional correlations among structures and may lack sensitivity and specificity. Here, we applied a novel voxel-based multivariate technique to a large ((18)F)2-fluoro-2-deoxy-D-glucose positron emission tomography data set. The sample consisted of 153 subjects, one-third each being probable subcortical VaD, probable Alzheimer disease (AD) (matched for Mini-Mental-State examination (MMSE) and age), and normal controls (NCs). We first applied principal component (PC) analysis and removed PCs significantly correlated to age. The remainders were used as feature vectors in a canonical variate analysis to generate canonical variates (CVs), that is, linear combinations of PC-scores. The first two CVs efficiently separated the groups. CV(1) separated VaD from AD with 100% accuracy, whereas CV(2) separated NC from demented subjects with 72% sensitivity and 96% specificity. Images depicting CV(1) and CV(2) showed that lower metabolism differentiating VaD from AD mainly concerned the deep gray nuclei, cerebellum, primary cortices, middle temporal gyrus, and anterior cingulate gyrus, whereas lower metabolism in AD versus VaD concerned mainly the hippocampal region and orbitofrontal, posterior cingulate, and posterior parietal cortices. The hypometabolic pattern common to VaD and AD mainly concerned the posterior parietal, precuneus, posterior cingulate, prefrontal, and anterior hippocampal regions, and linearly correlated with the MMSE. This study shows the potential of voxel-based multivariate methods to highlight independent functional networks in dementing diseases. By maximizing the separation between groups, this method extracted a metabolic pattern that efficiently differentiated VaD and AD.     

Addition of MHPG to Alzheimer's disease biomarkers improves differentiation of dementia with Lewy bodies from Alzheimer's disease but not other dementias

BackgroundOverlapping clinical features make it difficult to distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and other dementia types. In this study we aimed to determine whether the combination of cerebrospinal fluid (CSF) biomarkers, amyloid-β₄₂ (Aβ₄₂), total tau protein (t-tau), and phosphorylated tau protein (p-tau), in combination with 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), could be useful in discriminating DLB from vascular dementia (VaD) and frontotemporal dementia (FTD), as we previously demonstrated for differentiation of DLB from AD.MethodsWe retrospectively analyzed concentrations of MHPG, Aβ₄₂, t-tau, and p-tau in CSF in patients with DLB, AD, VaD, and FTD. Using previously developed multivariate logistic regression models we assessed the diagnostic value of these CSF parameters.ResultsThe currently used combination of Aβ₄₂, t-tau, and p-tau yielded a sensitivity of 61.9% and a specificity of 91.7% for the discrimination between DLB and AD, but could not discriminate between DLB and VaD or FTD. The addition of MHPG to Aβ₄₂, t-tau, and p-tau improves the discrimination of DLB from AD, yielding a sensitivity of 65.1% and specificity of 100%, but could not distinguish DLB from other forms of dementia.ConclusionsOur results confirm in a separate patient cohort that addition of MHPG to Aβ₄₂, t-tau, and p-tau improves the discrimination of DLB from AD but not the differentiation of DLB from VaD or FTD.     

Neuronal repair and replacement in spinal cord injury

OBJECTIVE: To assess age-, gender, and subtype-specific incidence rates of dementia in three populations in central Spain using data from the Neurological Disorders in Central Spain (NEDICES), a population-based survey of elderly participants. METHODS: Individuals were evaluated at baseline (1994-1995) and at follow-up (a median of 3.2 years later in 1997-1998). The evaluation included a screening questionnaire for dementia and a neurological assessment, when possible. RESULTS: Of 5278 participants evaluated at baseline, there were 306 prevalent dementia cases. One hundred and sixty-one incident dementia cases were identified among 3,891 individuals assessed at follow-up. The large majority had Alzheimer's disease (AD): 115 (71.4%) AD, 18 (11.2%) vascular dementia (VaD), 11 (6.8%) dementia associated with parkinsonism, 11 (6.8%) undetermined etiology, and 6 (3.7%) secondary dementia. Average annual incidence rates (per 1,000 person-years) in the population aged 65 to 90 and over years, adjusted to the standard European population, were 10.6 (95% CI, 8.9 to 12.3) for dementia, 7.4 (95% CI=6.0 to 8.8) for AD, and 1.4 (95% CI=0.6 to 2.3) for VaD. Age-specific incidence rates of dementia and AD increased exponentially with advancing age. Age, stroke and illiteracy were independent risk factors for dementia and AD. Aggregation of vascular risk factors was related to a higher risk of both VaD and AD. CONCLUSIONS: In the NEDICES study, incidence of dementia increased with age beyond age 85 and AD was the most frequent type of dementia. The risk of AD and VaD increased with the number of vascular risk factors.     

Neuropathological evaluation of mixed dementia

Mixed dementia (MD) refers to a combination of definite Alzheimer disease (AD) and vascular encephalopathy, but the distinction between both disorders is controversial. For the diagnosis of MD the clinical/neuroimaging criteria of possible AD plus cerebrovascular disease (CVD) as separate entities are used, but causal relations between vascular brain lesions and dementia are unclear. We proposed the combination of autopsy-proven AD with multiple vascular or ischemic lesions with about 30-50 ml of infarcted/damaged brain tissue. The population-based prevalence of MD is unknown. In retrospective and prospective autopsy studies, it ranges from 2 to 58% with reasonable means of 6-12%. In a consecutive autopsy series of 1500 demented elderly subjects, 830 of which with clinically probable AD, in Vienna, Austria, 41.5 to 52.0% showed "pure" AD, 7% atypical AD, 16-20% AD plus cerebrovascular lesions, and 9% AD plus Lewy body pathology; MD was diagnosed in 4.6 and 2.4%, and "pure" vascular dementia (VaD) in 11 and 2.0%, respectively, while 16.3/6.1% were other dementing disorders, and 1% showed no specific pathology. Like the MRC-CFAS and other studies, this indicates frequent coexistence of AD with multiple cerebrovascular lesions in cognitively impaired patients. In both AD and VaD, vascular lesions frequently involved subcortical regions (basal ganglia, thalamus, hippocampus, and white matter) or were multiple microinfarcts, whereas in MD, large/hemispheral infarcts and multiple microinfarcts were more frequent, suggesting different pathogenic mechanisms. In early/mild AD, critically located small vascular lesions may induce/promote cognitive decline, but in full-blown AD they appear of minor importance. Discussion of the major pathogenic factors inducing AD, VaD and MD suggests synergistic relations between these disorders. However, currently available morphological criteria for AD and VaD are of limited value for the diagnosis of MD and generally accepted and validated histopathological criteria for the diagnosis of VaD and MD are currently not available. Therefore, more distinct and critically evaluated clinico-pathological criteria are warranted.     

Criminal Behavior in the Four Years Preceding Diagnosis of Neurocognitive Disorder: A Nationwide Register Study in Finland

ObjectiveTo explore the criminality of patients with subsequent diagnosis of Alzheimer's disease (AD), frontotemporal dementia (FTD), or Lewy body dementias (LBD) in the four years preceding diagnosis.DesignNationwide register study.SettingData on Finnish patients were collected from the discharge register and data on criminal offending from the police register. Research findings were compared with the same-aged general population.ParticipantsA total of 92,191 patients who had received a diagnosis of AD (N = 80,540), FTD (N = 1,060), and LBD (N = 10,591) between 1998 and 2015.MeasurementsIncidences and types of crimes, the standardized criminality ratio (number of actual crimes per number of expected crimes), and the numbers of observed cases and person-years at risk counted in five-year age groups and separately for both genders and yearly.ResultsAt least one crime was committed by 1.6% of AD women and 12.8% of AD men, with corresponding figures of 5.3% and 23.5% in FTD, and 3.0% and 11.8% in LBD. The first crime was committed on average 2.7 (standard deviation 1.1) years before the diagnosis. The standardized criminality ratio was 1.85 (95% confidence interval [CI] 1.43–2.37) in FTD women and 1.75 (95% CI 1.54–1.98) in FTD men, and in AD 1.11 (95% CI 1.04–1.17) and 1.23 (95% CI 1.20–1.27), respectively. Traffic offences and crimes against property constituted 94% of all offences.ConclusionCriminal acts may occur several years prior to the diagnosis of dementia. If novel criminality occurs later in life, it may be associated with neurocognitive disorder.     

Diabetes mellitus is a risk factor for vascular dementia,but not for Alzheimer's disease: a population-based study of the oldest old

BACKGROUND: The purpose of this study was to examine if Type 2 diabetes mellitus is a risk factor for dementia in very old age, specifically for Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: We evaluated the risk of dementia in relation to Type 2 diabetes using a population-based sample of 702 individuals aged 80 years and older (mean age 83 years). A total of 187 persons received a dementia diagnosis. Thirty-one individuals had a diabetes diagnosis prior to onset of the dementia. RESULTS: Cox proportional hazard analyses, adjusted for age, gender, education, smoking habits, and circulatory diseases, indicated an elevated risk to develop VaD (relative risk = 2.54, 95% confidence interval 1.354.78) in individuals with diabetes mellitus. No association was found between diabetes and AD. CONCLUSION: Type 2 diabetes is selectively related to the different subtypes of dementia. There is no increased risk of AD but more than a twofold risk of VaD in persons with diabetes.