Systemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain.

By characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia.

Using the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively.

Our study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5–15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status.

This study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.

This study examined the association between loneliness and risk of incident all-cause dementia and whether the association extends to specific causes of dementia.

Longitudinal.

Community.

Participants were from the UK Biobank (N = 492,322).

None.

Loneliness was measured with a standard item. The diagnosis of dementia was derived from health and death records, which included all-cause dementia and the specific diagnoses of Alzheimer’s disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD), over 15 years of follow-up.

Feeling lonely was associated with a nearly 60% increased risk of all-cause dementia (HR = 1.59, 95% CI = 1.51–1.65; n = 7,475 incident all-cause). In cause-specific analyses, loneliness was a stronger predictor of VD (HR = 1.82, 95% CI = 1.62–2.03; n = 1,691 incident VD) than AD (HR = 1.40, 95% CI = 1.28–1.53; n = 3135 incident AD) and was, surprisingly, a strong predictor of FTD (HR = 1.64, 95% CI = 1.22–2.20; n = 252 incident FTD). The associations were robust to sensitivity analyses and were attenuated but remained significant accounting for clinical (e.g. diabetes) and behavioral (e.g. physical activity) risk factors, depression, social isolation, and genetic risk. The association between loneliness and all-cause and AD risk was moderated by APOE ϵ4 risk status such that the increased risk was apparent in both groups but stronger among non-carriers than carriers of the risk allele.

Loneliness is associated with increased risk of multiple types of dementia.

Vascular dementia (VaD) accounts for approximately 15% of all cases of dementia. While there are many different definitions of vascular dementia, it is generally understood to refer to “disease with a cognitive impairment resulting from cerebrovascular disease and ischaemic or haemorrhagic brain injury”. Research suggests that 30% of patients with VaD also suffer from depression. The treatment of depression in VaD with pharmacological therapy is relatively well-established, with the first line drug being a selective serotonin reuptake inhibitor (SSRI). However, a relatively under-researched area is the use of brain stimulation and neuromodulation therapies for the treatment of depression in VaD.

This review aims to provide a critical analysis on the efficacy and safety of brain stimulation therapies in treating depression in VaD to determine whether it is an appropriate treatment option.

The databases used were PubMed and WebofScience. The available literature was analysed which resulted in three papers which met the inclusion criteria and were critically appraised.

In all three studies, depressive symptoms improved after ECT was administered, regardless of the specific tool used to measure the severity of depression. The side effects experienced were also only temporary and resolved independently which speaks to the safety of ECT as a treatment option.

The results of the study prove that ECT is a safe and effective option in treating depression in VaD. However, more research is needed for the medical community to fully understand the different treatment options and say with certainty which is the safest and most effective.

No significant relationships.

A large proportion of Alzheimer’s disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity.

To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD.

We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures.

Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD).

These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.

To investigate factors associated with suicidal ideation (SI) around the time of dementia diagnosis. We hypothesised relatively preserved cognition, co-occurring physical and psychiatric disorders, functional impairments, and dementia diagnosis subtype would be associated with a higher risk of SI.

Cross-sectional study using routinely collected electronic mental healthcare records.

National Health Service secondary mental healthcare services in South London, UK, serving a population of over 1.36 million residents.

Patients who received a diagnosis of dementia (Alzheimer’s, vascular, mixed Alzheimer’s/vascular, or dementia with Lewy bodies) between 1 Nov 2007–31 Oct 2021: 18,252 people were identified during the observation period.

A natural language processing algorithm was used to identify recorded clinician recording of SI around the time of dementia diagnosis. Sociodemographic and clinical characteristics were also measured around the time of diagnosis. We compared people diagnosed with non-Alzheimer’s dementia to those with Alzheimer’s and used statistical models to adjust for putative confounders.

15.1% of patients had recorded SI, which was more common in dementia with Lewy bodies compared to other dementia diagnoses studied. After adjusting for sociodemographic and clinical factors, SI was more frequent in those with depression and dementia with Lewy bodies and less common in those with impaired activities of daily living and in vascular dementia. Agitated behavior and hallucinations were not associated with SI in the final model.

Our findings highlight the importance of identifying and treating depressive symptoms in people with dementia and the need for further research into under-researched dementia subtypes.

The most frequent and severe non-cognitive disorders in dementia are hallucinatory-paranoid disorders (HPD), which cause social dysfunction and financial burden of this pathology.

To study the features of HPD in vascular dementia (VD), an approach using clinical-psychopathological, psychometric, psychodiagnostic and mathematical-statistical methods was used.

The study was based on the examination of 75 patients with HPD in VD and 63 patients with VD without HPD.

In patients with VD in the middle stage of development in the structure of clinical manifestations was dominated by frequent paranoid and paranoid disorders (in 75.6% of patients, p <0.05) with a systemic delusional plot (in 70.1% of patients, p <0.01) material damage, robbery, theft (in 26.8% of patients, p <0.01), relationships (in 21.9% of patients, p <0.01) and jealousy (in 17.1% of patients, p <0, 01), which ran in the form of paranoid delusional disorder (63.4%), acute paranoia (12.2%) and hallucinations (24.4%). In patients with VD in the late stage of development, the clinical and psychopathological structure of GPR was characterized by a predominance of frequent, hallucinatory disorders (82.4% of patients, p <0.01) in the form of healthy (23.5%, p <0.1), tactile (20.6%, p <0.01) and auditory (26.5%, p <0.5) hallucinations, which took the form of hallucinations (44.2%, p <0.05), confusion (61.5 %, p <0.05) and paranoid delusional disorder (17.6%, p <0.01).

The study of the clinical and psychopathological structure of HPD in patients with dementia of different stages of development revealed their dependence on the stage of development of the pathological process.

Patients diagnosed with vascular dementia often present with apathy, executive dysfunction or/and memory impairment. Some of these psychiatric domains are not responsive to antidepressants or acetylcholinesterase inhibitors. Since methylphenidate enhances frontal lobe function, it may be a valid therapeutic option.

To report a case where methylphenidate was used as a therapeutic approach in vascular dementia.

We present a case of a patient diagnosed with vascular dementia with substantial clinical improvement after treatment with methylphenidate.

A 67 year-old male was observed in a psychiatric consultation reporting memory loss, inability to retain information and inattention. According to her spouse, the patient has been mostly isolated at home and recently he has become unable to accomplish some daily living activities. There was no history of previous psychiatric disorder. Cognitive assessment was performed using MoCA test: 19/30 points (predominantly in executive, attention and delayed recall domains). After this evaluation, it was introduced bupropion 150mg od and donepezil 5mg od with insignificant clinical improvement. The patient underwent a routine workup which was unremarkable and a brain computed tomography scan that revealed ischemic leukoencephalopathy. Three months later no clinical benefit was reported. Attention and functional improvement were observed after introduction of methylphenidate with progressive dose adjusting till 30 mg/day.

Besides not being a consensual therapeutic approach, considering that there is a lack of efficient pharmacological strategies in vascular dementia, methylphenidate may play a significant role in this field contributing to clinical improving and ultimately to an enhanced quality of life.

To describe the neuroimaging and other methods for assessing vascular contributions to neurodegeneration in the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study, a Canadian multi-center, prospective longitudinal cohort study, including reliability and feasibility in the first 200 participants.

COMPASS-ND includes persons with Alzheimer’s disease (AD; n = 150), Parkinson’s disease (PD) and Lewy body dementias (LBDs) (200), mixed dementia (200), mild cognitive impairment (MCI; 400), subcortical ischemic vascular MCI (V-MCI; 200), subjective cognitive impairment (SCI; 300), and cognitively intact elderly controls (660). Magnetic resonance imaging (MRI) was acquired according to the validated Canadian Dementia Imaging Protocol and visually reviewed by either of two experienced readers blinded to clinical characteristics. Other relevant assessments include history of vascular disease and risk factors, blood pressure, height and weight, cholesterol, glucose, and hemoglobin A1c.

Analyzable data were obtained in 197/200 of whom 18 of whom were clinically diagnosed with V-MCI or mixed dementia. The overall prevalence of infarcts was 24.9%, microbleeds was 24.6%, and high white matter hyperintensity (WMH) was 31.0%. MRI evidence of a potential vascular contribution to neurodegeneration was seen in 12.9%–40.0% of participants clinically diagnosed with another condition such as AD. Inter-rater reliability was good to excellent.

COMPASS-ND will be a useful platform to study vascular brain injury and its association with risk factors, biomarkers, and cognitive and functional decline across multiple age-related neurodegenerative diseases. Initial findings show that MRI-defined vascular brain injury is common in all cognitive syndromes and is under-recognized clinically.

In observational studies, type-2 diabetes is associated with increased risk of dementia; however, the causal nature of this association remains unanswered. In an unselected nationwide study of all Danes, we wanted to test whether type-2 diabetes is associated with dementia subtypes, and to test whether potential associations are of a causal nature.

In the current study of nationwide observational registry data in all Danes above the age of 65 years (n = 784 434) combined with genetic consortia data on 213 370 individuals, we investigated the associations between type-2 diabetes and Alzheimer's disease, vascular dementia, unspecified dementia and all-cause dementia, and whether observational associations were of a causal nature by applying a two-sample Mendelian randomisation strategy. We addressed key biases inherent in Mendelian randomisation approaches.

Important confounders (age, ethnicity, size of community, region, civil status and education level) were captured on all 784 434 individuals and adjusted for in the models. Multifactorial adjusted hazard ratios were 1.13 (1.06–1.21) for Alzheimer's disease, 1.98 (1.83–2.14) for vascular dementia, 1.53 (1.48–1.59) for unspecified dementia and 1.48 (1.44–1.53) for all-cause dementia in persons with type-2 diabetes v. without. Results were similar for men and women. The two-sample Mendelian randomisation estimate for the association between the genetic instrument and Alzheimer's disease was 1.04 (0.98–1.10), consistent with sensitivity estimates, addressing pleiotropy, measurement bias and weak instrument bias.

In a nationwide study of all Danes above the age of 65 years, we show that type-2 diabetes is associated with major subtypes of dementia – with particularly strong associations for vascular dementia and unspecified dementia – the two types of dementia with the most obvious vascular pathologies. Although the present two-sample Mendelian randomisation approach using genetic consortia data suggests that type-2 diabetes is not a direct cause of Alzheimer's disease, we were unable to test the causal nature of type-2 diabetes for vascular dementia and unspecified dementia, because no publicly available genetic consortia data yet exist for these dementia endpoints. The causal nature of type-2 diabetes for dementia with vascular pathologies is pivotal questions to solve for future public health recommendations and therapeutic advice.

Ischemic stroke can lead to heart injury via dysfunction of the autonomic nervous system. QT intervals on electrocardiography (ECG) are susceptible to autonomic influences and their prolongation was associated with increased mortality after stroke.

We aimed to study QT intervals in patients with ischemic stroke in chronic phase with and without cognitive impairment.

ECGs were recorded in 50 patients with ischemic stroke. QT interval corrected for heart rate (QTc), QT dispersion (QTd), and QT interval variability (QTIV) were measured. The QTVI was calculated as the logarithm of the ratio between the variances of the normalized QT and RR intervals. Using Mini Mental State Examination and Hachinski's ischemic scale we identified vascular dementia (VaD) in 17 patients. Twenty age-matched healthy subjects were examined for comparison.

We identified QTc, QTd prolongation in patients with ischemic stroke. Comparing patients with ischemic stroke vs. VaD, QTc (412 ±75.2 ms vs 456± 115 ms, p<0.01) and QTd (64±14ms vs 154±69 ms, p<0.0001) were more prolonged in VaD. QTVI were generally increased in ischemic stroke patients compared with healthy subjects (p<0.05) but the differences with high statistical significance level were found in VaD patients (p<0.001). We found correlation between QTd, QTVI, hypertension, diabetes, arrhythmia and cognitive impairment.

Prolongation of QT intervals and increased QTVI occurs frequently after ischemic stroke but most significant changes were found in patients with cognitive impairment. Early detection of cognitive impairment in stroke patients provides better prevention of possible dementia.