Biomarkers.

Background: Single molecule array (Simoa) technology enables the detection of Alzheimer's disease (AD) neuropathology in blood. This study compared cross-sectional biomarker profiles for participants from the New Zealand-Dementia Prevention Research Clinics (NZ-DPRCs) who spanned the continuum from healthy older adults to a clinical diagnosis of AD.

Method: NZ-DPRC participants were clinically classified as cognitively unimpaired adults (CU, n=34), subjective cognitive decline (SCD, n=65), non-amnestic mild cognitive impairment (single and multi-domain, non-aMCI, n= 23), amnestic MCI (single and multi-domain, aMCI, n=104), and AD (n=27).

Biomarkers.

Background: Establishing practical and effective diagnostic pathways for people with cognitive impairment is a crucial international research priority. Traditional (late-phase) analysis of an amyloid-beta (Aβ) PET scan (∼90 minutes after radiotracer injection) provides important information about the presence/absence of underlying Alzheimer's pathology, but no information about brain metabolism/perfusion. Recent work suggests that amyloid-beta PET tracer uptake shortly after injection ('early-phase') closely reflects brain metabolism and perfusion.

Public Health.

Background: The projected doubling of dementia prevalence by 2050 highlights the critical importance of altering the dementia trajectory and associated burden. Modifiable risk factors account for 40% of dementia risk (Livingston et al, 2020), including physical inactivity in late life. Protective effects of physical activity (PA) may be greater during earlier stages of neuropathological change, either directly by influencing the brain, or, indirectly by protecting against hypertension, obesity, and diabetes.

Biomarkers.

Background: Normal cognitive function is supported by the neuromodulatory mechanisms of the cholinergic system. In Parkinson's disease (PD), histological and molecular imaging evidence suggests disruption to cholinergic circuitry is associated with progression to Parkinson's disease dementia (PDD). The primary source of cortical cholinergic input is the Ch4 region of the basal forebrain.

Developing Topics.

Background: Brain connectivity patterns, measured with Magnetic Resonance Imaging (MRI), have been recently studied as a potential biomarker for Alzheimer's disease dementia (AD). A 'disconnected brain' has been associated with greater cognitive impairment in pathological aging (Bennett & Madden, 2014), but it is unclear how this occurs in groups at risk of AD.

Method: Participants (n = 227; aged 55+ years) from the Dementia Prevention Research Clinic, New Zealand, were classified as control (C; n = 35), subjective cognitive decline (SCD; n = 60), single-domain amnestic mild cognitive impairment (aMCI; n = 54), multiple-domain MCI (mMCI; n = 52), and AD (n = 26).

A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease.

Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson's disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium.

Higher Frequency of Stuttered Disfluencies Negatively Affects Communicative Participation in Parkinson's Disease.

Purpose: Up to 90% of people with Parkinson's disease (PD) develop communication difficulties over the course of the disease. While the negative effect of dysarthria on communicative participation has been well-documented, the impact of the occurrence of acquired stuttered disfluencies on communication in different speech situations is unknown. This study aimed to determine if the frequency of occurrence of stuttered disfluencies affects communicative participation in individuals with PD, and whether such a relationship is mediated by examiner- and self-rated measures of disease severity.

An estimate of the longitudinal pace of aging from a single brain scan predicts dementia conversion, morbidity, and mortality.

To understand how aging affects functional decline and increases disease risk, it is necessary to develop accurate and reliable measures of how fast a person is aging. Epigenetic clocks measure aging but require DNA methylation data, which many studies lack. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain MRI: the Dunedin Pace of Aging Calculated from NeuroImaging or DunedinPACNI.

A worldwide study of white matter microstructural alterations in people living with Parkinson's disease.

The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences.

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals.

Early-phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease.

Introduction: Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD.

Methods: One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments.

Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

Background: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated.

Objective: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group.

Acquired Stuttering in Parkinson's Disease.

Background: Parkinson's disease frequently causes communication impairments, but knowledge about the occurrence of new-onset stuttering is limited.

Objectives: To determine the presence of acquired neurogenic stuttering and its relationship with cognitive and motor functioning in individuals with Parkinson's disease.

Method: Conversation, picture description, and reading samples were collected from 100 people with Parkinson's disease and 25 controls to identify the presence of stuttered disfluencies (SD) and their association with neuropsychological test performance and motor function.

Altered nucleus accumbens functional connectivity precedes apathy in Parkinson's disease.

Work in animal and human neuroscience has identified neural regions forming a network involved in the production of motivated, goal-directed behaviour. In particular, the nucleus accumbens and anterior cingulate cortex are recognized as key network nodes underlying decisions of whether to exert effort for reward, to drive behaviour. Previous work has convincingly shown that this cognitive mechanism, known as effort-based decision making, is altered in people with Parkinson's disease with a syndrome of reduced goal-directed behaviour-apathy.

Dementia Prevention Research Clinic: a longitudinal study investigating factors influencing the development of Alzheimer's disease in Aotearoa, New Zealand.

Aotearoa New Zealand's population is ageing. Increasing life expectancy is accompanied by increases in prevalence of Alzheimer's Disease (AD) and ageing-related disorders. The multicentre Dementia Prevention Research Clinic longitudinal study aims to improve understanding of AD and dementia in Aotearoa, in order to develop interventions that delay or prevent progression to dementia.

Non-Contact Hand Movement Analysis for Optimal Configuration of Smart Sensors to Capture Parkinson's Disease Hand Tremor.

Parkinson’s disease affects millions worldwide with a large rise in expected burden over the coming decades. More easily accessible tools and techniques to diagnose and monitor Parkinson’s disease can improve the quality of life of patients. With the advent of new wearable technologies such as smart rings and watches, this is within reach.

Spatial variation of perfusion MRI reflects cognitive decline in mild cognitive impairment and early dementia.

Cerebral blood flow (CBF) measured with arterial spin labelling (ASL) magnetic resonance imaging (MRI) reflects cerebral perfusion, related to metabolism, and arterial transit time (ATT), related to vascular health. Our aim was to investigate the spatial coefficient of variation (sCoV) of CBF maps as a surrogate for ATT, in volunteers meeting criteria for subjective cognitive decline (SCD), amnestic mild cognitive impairment (MCI) and probable Alzheimer's dementia (AD). Whole-brain pseudo continuous ASL MRI was performed at 3 T in 122 participants (controls = 20, SCD = 44, MCI = 45 and AD = 13) across three sites in New Zealand.

International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease.

Background: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated.

Objective: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging.

Methods: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources.

Higher perceived stress and exacerbated motor symptoms in Parkinson's disease during the COVID-19 lockdown in New Zealand.

Aims: Stress plays a key role in Parkinson's disease (PD) by acting on the dopaminergic system and worsening patients' motor function. The impact of New Zealand's strict lockdown measures to contain COVID-19 on perceived stress and PD motor symptoms remains unknown. Here we examined the relationship between perceived levels of stress, changes in physical activity levels and PD motor symptoms during lockdown.

Neuropsychiatric Symptoms Are Associated with Dementia in Parkinson's Disease but Not Predictive of it.

Background: Neuropsychiatric symptoms in Parkinson's disease (PD) may increase dementia (PDD) risk. The predictive value of these symptoms, however, has not been compared to clinical and demographic predictors of future PDD.

Objectives: Determine if neuropsychiatric symptoms are useful markers of PDD risk.

Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders.

Background: People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease.

Variations in the patterns of prevalence and therapy in Australasian Parkinson's disease patients of different ethnicities.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly after Alzheimer's disease. It is expected that PD cumulative incidence will increase in the future, as there are far more people surviving into late age than there ever used to be. While most commonly idiopathic, rare forms of PD can be familial/genetic.