The risk of developing dementia in the COVID-19 pandemic; a cohort study.

OBJECTIVES: The effects of the COVID-19 pandemic on cognitive decline are not fully understood. Higher social activity and relationships have been associated with decreased risk of dementia. We hypothesised that risk of transition to dementia would increase after the start of the first national lockdown. METHODS: We obtained data from the Brains for Dementia (BDR) cohort, which has collected roughly annual data on 3726 older adults with and without dementia since 2008. Data continued to be collected during the lockdowns, although by telephone and/or video call instead of in person. Individuals diagnosed with dementia at study entry were excluded from this study as were individuals with only one visit. Cognitive status was classified using the Clinical Dementia Rating (CDR) global score. Poisson regression with cubic splines to account for differences in age was used to compare the incidence of dementia before and after March 1st 2020. RESULTS: Out of 2242 individuals, 208 individuals developed dementia before and 50 developed dementia after 01/03/20. The incidence rate ratio of developing dementia after 01/03/20 was 0.847 (0.538-1.335) p = 0.570. In our secondary analysis we found that the positive association between mild cognitive impairment (MCI) and dementia incidence decreased after 1/3/20 (interaction effect p = 0.031). CONCLUSION: The incidence of dementia as defined using the CDR global score did not change significantly after the first lockdown began, but we found evidence that lockdown decreased the positive association between MCI and dementia incidence. This may reflect that individuals were progressing to dementia more rapidly and thus missing the MCI stage or that assessing patients over the phone made diagnosing MCI more challenging.

Persistent depressive symptoms are associated with frontal regional atrophy in patients with Alzheimer's disease.

BACKGROUND: Depression in individuals with Alzheimer's disease (AD) is common, difficult to treat and inadequately understood. Previous studies have identified possible differences in regional brain atrophy in individuals with AD and depression, but the results have been inconsistent and some studies had less robust definitions of depression. We aimed to examine regional brain atrophy in two large dementia focused cohorts. METHODS: We used data from Alzheimer's disease neuroimaging initiative (ADNI) and the National Alzheimer's Co-ordinating Center (NACC), for those with data from at least one MRI scan. Depression ratings were available using the Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory (NPI). Intermittent depressive symptoms were defined as one episode above threshold (≥8 on GDS, ≥6 on NPI depression subscale and ≥2 on the Neuropsychiatric Inventory version Q depression sub-scale) and persistent as ≥2 episodes. Derived regional volumetric data was available from ADNI and the NACC. RESULTS: Data was available from 698 individuals with AD in NACC and from 666 individuals in ADNI. We found no evidence of between group differences in regional brain volume at baseline, or of differential atrophy in NACC. In ADNI we found evidence of increased brain atrophy in several frontal brain areas. LIMITATIONS: Because this study was limited to those with MRI data, the numbers in some analyses were low. MRI parcellation differed between studies making direct comparison difficult. For some individuals only the NPI was used to rate depression. CONCLUSIONS: We have found mixed evidence of increased regional atrophy in depression in AD, mainly in frontal brain regions. We found no evidence to support a vascular basis for depression in AD.

Does depression in mid-life predispose to greater cognitive decline in later life in the Whitehall II cohort?

BACKGROUND: Later-life depression appears to have different symptomatology and possibly underlying pathology to younger adults. Depression is linked to dementia but whether it is a risk factor or an early sign of dementia remains unclear. Neuroinflammation is increasingly recognised in both conditions. AIMS: To investigate the link between depression, inflammation and dementia. We hypothesised that recurrent depression increases the rate of cognitive decline in older adults and that this effect is modified by anti-inflammatory medication. METHODS: We used data from Whitehall II including cognitive test results and reliable measures to assess depression. Depression was defined as a self-reported diagnosis or a score of ≥20 on the CESD. The presence/absence of inflammatory illness was assessed using a standardised list of inflammatory conditions. Individuals with dementia, chronic neurological and psychotic conditions were excluded. Logistic and linear regression was used to examine the effect of depression on cognitive test performance and the effect of chronic inflammation. LIMITATIONS: Lack of clinical diagnoses of depression. RESULTS: There were 1063 individuals with and 2572 without depression. Depression did not affect deterioration in episodic memory, verbal fluency or the AH4 test at 15-year follow up. We found no evidence of an effect of anti-inflammatory medication. Depressed individuals had worse cross-sectional performance on the Mill Hill test and tests of abstract reasoning and verbal fluency at both baseline and 15-year follow-up. CONCLUSIONS: Using a UK based study with a long follow-up interval we have shown that depression in individuals aged >50 is not associated with increased cognitive decline.

What neuroscience has already done for us.

SUMMARY: Each of the components of the biopsychosocial model of mental illness is important for understanding mental illness. Biological and genetic abnormalities have been demonstrated in major mental illnesses. These are leading to changes in our understanding of these conditions, as well as our understanding of the link between life events and mental illness.

Visual hallucinations in Alzheimer's disease do not seem to be associated with chronic hypoperfusion of to visual processing areas V2 and V3 but may be associated with reduced cholinergic input to these areas.

BACKGROUND: Up to 20% of patients with AD experience hallucinations. The pathological substrate is not known. Visual hallucinations (VH) are more common in dementia with Lewy bodies (DLB). In autopsy studies, up to 60% of patients with AD have concomitant Lewy body pathology. Decreased perfusion of the occipital lobe has been implicated in DLB patients with VH, and post-mortem studies point to both decreased cholinergic activity and reduced oxygenation of the occipital cortex in DLB. METHODS: We used biochemical methods to assess microvessel density (level of von Willebrand factor, a marker of endothelial cell content), ante-mortem oxygenation (vascular endothelial growth factor, a marker of tissue hypoxia; myelin-associated glycoprotein to proteolipid protein-1 ratio, a measure of tissue oxygenation relative to metabolic demand), cholinergic innervation (acetylcholinesterase and choline acetyltransferase), butyrylcholinesterase and insoluble α-synuclein content in the BA18 and BA19 occipital cortex obtained post-mortem from 23 AD patients who had experienced visual hallucinations, 19 AD patients without hallucinations, 19 DLB patients, and 36 controls. The cohorts were matched for age, gender and post-mortem interval. RESULTS: There was no evidence of reduced microvessel density, hypoperfusion or reduction in ChAT activity in AD with visual hallucinations. Acetylcholinesterase activity was reduced in both BA18 and BA19, in all 3 dementia groups, and the concentration was also reduced in BA19 in the DLB and AD without visual hallucinations groups. Insoluble α-synuclein was raised in the DLB group in both areas but not in AD either with or without visual hallucinations. CONCLUSIONS: Our results suggest that visual hallucinations in AD are associated with cholinergic denervation rather than chronic hypoperfusion or α-synuclein accumulation in visual processing areas of the occipital cortex.