Effects of a 6-month cognitive intervention program on brain metabolism in amnestic mild cognitive impairment and mild Alzheimer's disease

The effect of cognitive intervention on brain metabolism in Alzheimer's disease (AD) is largely unexplored. Therefore, we aimed to investigate clinical cognitive parameters and 18FDG PET to test for effects of a cognitive intervention in patients with amnestic mild cognitive impairment (aMCI) or mild AD. Patients with aMCI (n = 24) or mild AD (n = 15) were randomly assigned either to cognitive intervention groups (IGs), receiving weekly sessions of group-based multicomponent cognitive intervention, or active control groups (CGs), receiving pencil-paper exercises for self-study. We obtained resting-state FDG-PET scans and neuropsychological testing at baseline and after six-months. Normalized FDG-PET images were analyzed using voxel-based SPM5 approaches to determine longitudinal changes, group-by-time interactions, and correlations with neuropsychological outcome parameters. Primary global cognitive outcome was determined by analyses of covariance with MMSE and ADAS-cog scores as dependent measures. Both, aMCI and AD subgroups of CGs showed widespread bilateral cortical declines in FDG uptake, while the AD subgroup of IGs showed discrete decline or rather no decline in case of the aMCI subgroup. Group by time analyses revealed strongest attenuation of metabolic decline in the aMCI subgroup of the IGs, involving left superior temporal- and anterior cingulate gyrus. However, correlation analyses revealed only weak non-significant associations between increased FDG uptake and improvement in primary or secondary outcome parameters. Concurrently, there was significant improvement in global cognitive status in the aMCI subgroup of the IGs. A six-month cognitive intervention imparted cognitive benefits in patients with aMCI, which were concurrent with an attenuated decline of glucose metabolism in cortical regions affected by neurodegenerative AD.     

Effects of a newly developed cognitive intervention in amnestic mild cognitive impairment and mild Alzheimer's disease: a pilot study

Recent studies have shown that patients with Alzheimer's disease (AD) and its possible prodromal stage mild cognitive impairment benefit from cognitive interventions. Few studies so far have used an active control condition and determined effects in different stages of disease. We evaluated a newly developed 6-month group-based multicomponent cognitive intervention in a randomized controlled pilot study on subjects with amnestic mild cognitive impairment (aMCI) and mild AD patients. Forty-three subjects with aMCI and mild AD were recruited. Primary outcome measures were change in global cognitive function as determined by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Mini Mental Status Examination (MMSE). Secondary outcomes were specific cognitive and psychopathological ratings. Thirty-nine patients were randomized to intervention groups (IGs: 12 aMCI, 8 AD) and active control groups (CGs: 12 aMCI, 7 AD). At the end of the study, we found significant improvements in the IG(MCI) compared to the CG(MCI) in the ADAS-cog (p = 0.02) and for the secondary endpoint Montgomery Asberg Depression Rating Scale (MADRS) (p < 0.01) Effects on the MMSE score showed a non-significant trend (p = 0.07). In AD patients, we found no significant effect of intervention on the primary outcome measures. In conclusion, these results suggest that participation in a 6-month cognitive intervention can improve cognitive and non-cognitive functions in aMCI subjects. In contrast, AD patients showed no significant benefit from intervention. The findings in this small sample support the use of the intervention in larger scales studies with an extended follow-up period to determine long-term effects.     

Cortical brain metabolism as measured by proton spectroscopy is related to memory performance in patients with amnestic mild cognitive impairment and Alzheimer's disease

AIMS: To investigate the relationship between verbal memory performance and brain metabolism as determined by proton spectroscopy ((1)H-MRS) in selected cortical brain regions. To characterize metabolite abnormalities across the continuum of degenerative disease from mild impairment to dementia. METHODS: 27 controls, 27 amnestic mild cognitive impairment (aMCI) patients and 35 Alzheimer's disease (AD) patients. Verbal memory was assessed with the Text Memory Test, the Wordlist Learning Test (WL-Learning Test), and with a memory screening test, the Memory Alteration Test (M@T). Single-voxel (1)H-MRS was obtained in the posterior cingulate (P-CING), left temporal pole (L-TPOLE) and left posterior temporoparietal region (L-TPAR). RESULTS: WL-Learning Test scores were inversely associated with myoinositol/creatine ratios (mI/Cr) in the L-TPAR (r = -0.404, p < 0.002). Negative associations were also observed between M@T global scores and mI/Cr in the P-CING (r = -0.42; p < 0.001), L-TPOLE (r = -0.34; p < 0.005) and L-TPAR (r = -0.46; p < 0.001). A positive association was found between M@T scores and N-acetylaspartate concentrations in the P-CING (r = 0.33; p < 0.003). CONCLUSION: Verbal learning performance is related to metabolic changes in cortical brain regions known to be involved in the neurodegenerative process of aMCI and AD.     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.     

High rate of conversion to Alzheimer's disease in a cohort of amnestic MCI patients

BACKGROUND: A large proportion of patients with amnestic mild cognitive impairment (MCI) progress to Alzheimer's disease (AD), but the rate of conversion is highly variable, depending on selection and inclusion criteria. In the present prospective study, amnestic MCI criteria were applied in order to enrich the study population with prodromal AD patients. METHODS: A composite CERAD word list learning z-score of -1 was applied as a cut-off for memory performance at baseline. Competing causes of memory impairment other than prodromal AD were actively excluded. A cohort of 88 amnestic MCI patients was included; 75 were available for follow-up. RESULTS: After a mean delay of 19 months, 44% were found to have converted to AD, corresponding to an annualized conversion rate of 28%. The rate of new diagnoses other than stable MCI or AD was 6%. Baseline neuropsychological variables were not instrumental to predict progression. CONCLUSION: Amnestic MCI patients, as identified by the present set of criteria, carry a high risk of median-term progression to AD.     

Oxidative and nitrosative modifications of biliverdin reductase-A in the brain of subjects with Alzheimer's disease and amnestic mild cognitive impairment

Biliverdin reductase-A (BVR-A) is a pleiotropic enzyme and plays pivotal role in the antioxidant defense against free radicals as well as in cell homeostasis. Together with heme oxygenase, BVR-A forms a powerful system involved in the cell stress response during neurodegenerative disorders including Alzheimer's disease (AD), whereas due to the serine/threonine/tyrosine kinase activity the enzyme regulates glucose metabolism and cell proliferation. In this paper, we report results that demonstrate BVR-A undergoes post-translational oxidative and nitrosative modifications in the hippocampus, but not cerebellum, of subjects with AD and amnestic mild cognitive impairment (MCI). A significant increase of nitrated BVR-A was demonstrated only in AD and MCI hippocampi, whereas no significant modifications were found in cerebellar tissue. In addition, a significant reduction in protein carbonyl-derivatives of BVR-A was found in both AD and MCI hippocampi (15% and 18%, respectively). Biliverdin reductase-bound 4-hydroxynonenals were not modified in hippocampi and cerebella from AD and MCI subjects. These results supported the hypothesis of a prevalence of nitrosative stress-induced modifications on BVR-A structure, and this evidence was confirmed by a significant upregulation of inducible nitric oxide synthase in hippocampal tissue of subjects with AD and MCI that was not present in cerebellum. In conclusion, nitrosative stress-induced modifications on hippocampal BVR-A are an early event in the pathogenesis of AD since they appear also in MCI subjects and could contribute to the antioxidant and metabolic derangement characteristic of these neurodegenerative disorders.     

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease

Background:  Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned.
Methods:  We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls.
Results:  Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices.
Discussion:  We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD.     

Association between cognitive performance and cortical glucose metabolism in patients with mild Alzheimer's disease

BACKGROUND: Neuronal and synaptic function in Alzheimer's disease (AD) is measured in vivo by glucose metabolism using positron emission tomography (PET). OBJECTIVE: We hypothesized that neuronal activation as measured by PET is a more sensitive index of neuronal dysfunction than activity during rest. We investigated if the correlations between dementia severity as measured with the Mini Mental State Examination (MMSE) and glucose metabolism are an artifact of brain atrophy. METHOD: Glucose metabolism was measured using [18F]fluorodeoxyglucose PET during rest and activation due to audiovisual stimulation in 13 mild to moderate AD patients (MMSE score > or = 17). PET data were corrected for brain atrophy. RESULTS: In the rest condition, glucose metabolism was correlated with the MMSE score primarily within the posterior cingulate and parietal lobes. For the activation condition, additional correlations were within the primary and association audiovisual areas. Most local maxima remained significant after correcting for brain atrophy. CONCLUSION: PET activity measured during audiovisual stimulation was more sensitive to functional alterations in glucose metabolism in AD patients compared to the resting PET. The association between glucose metabolism and MMSE score was not dependent on brain atrophy.     

Orientational changes of white matter fibers in Alzheimer's disease and amnestic mild cognitive impairment

White matter abnormalities represent early neuropathological events in neurodegenerative diseases such as Alzheimer''s disease (AD), investigating these white matter alterations would likely provide valuable insights into pathological changes over the course of AD. Using a novel mathematical framework called “Director Field Analysis” (DFA), we investigated the geometric microstructural properties (i.e., splay, bend, twist, and total distortion) in the orientation of white matter fibers in AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) individuals from the Alzheimer''s Disease Neuroimaging Initiative 2 database. Results revealed that AD patients had extensive orientational changes in the bilateral anterior thalamic radiation, corticospinal tract, inferior and superior longitudinal fasciculus, inferior fronto‐occipital fasciculus, and uncinate fasciculus in comparison with CN. We postulate that these orientational changes of white matter fibers may be partially caused by the expansion of lateral ventricle, white matter atrophy, and gray matter atrophy in AD. In contrast, aMCI individuals showed subtle orientational changes in the left inferior longitudinal fasciculus and right uncinate fasciculus, which showed a significant association with the cognitive performance, suggesting that these regions may be preferential vulnerable to breakdown by neurodegenerative brain disorders, thereby resulting in the patients'' cognitive impairment. To our knowledge, this article is the first to examine geometric microstructural changes in the orientation of white matter fibers in AD and aMCI. Our findings demonstrate that the orientational information of white matter fibers could provide novel insight into the underlying biological and pathological changes in AD and aMCI.     

Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment

Objective Aim of this study was to find cerebral perfusion correlates of conversion to dementia in patients with amnestic MCI. Methods 17 healthy subjects (age = 69 ± 3, 9 females), and 23 amnestic MCI patients (age = 70 ± 6, 10 females) underwent brain MR scan and ^99mTc ECD SPECT. Conversion to AD was ascertained on average 19 ± 10 months after baseline: 9 had converted (age = 69 ± 3, 4 females), and 14 had not (age = 71 ± 8, 6 females). We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing amnestic MCI patients converted to AD and non-converted to dementia vs controls. We assessed the effect of gray matter atrophy on the above results with SPM2 using an optimized Voxel-Based Morphometry (VBM) protocol.We compared significant hypoperfusion with significant atrophy on a voxel-byvoxel basis. Results In comparison with normal controls, amnestic MCI patients who converted to AD showed hypoperfusion in the right parahippocampal gyrus and left inferior temporal and fusiform gyri,whereas those who did not convert showed hypoperfusion in the retrosplenial cortex, precuneus and occipital gyri, mainly on the left side.We found no overlap between significant atrophy and significant hypoperfusion regions. Conclusions Parahippocampal and inferior temporal hypoperfusion in amnestic MCI patients appears as a correlate of conversion to AD; hypoperfusion in the retrosplenial cortex is involved in memory impairment but does not seem the key prognostic indicator of conversion to dementia.     

Multiple diffusivities define white matter degeneration in amnestic mild cognitive impairment and Alzheimer's disease

Different diffusivity measurements in diffusion-tensor imaging (DTI) could be helpful for detecting the distinct mechanisms of white matter degeneration in Alzheimer's disease (AD). However, few studies have explored the changes of white matter in amnestic mild cognitive impairment (aMCI) and AD by whole-brain voxel-wise analyses of all diffusivity indices. The association between grey matter atrophy and white matter damage measured by distinct diffusivities is still uncertain. Structural magnetic resonance imaging and DTI with four diffusivity indices, comprising fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, were performed in 30 normal controls, 26 mild AD patients, and 40 aMCI patients with isolated memory impairment. T1 voxel-based morphometry and DTI tract-based spatial statistics were applied to compare the grey and white matter changes in the 3 groups. In contrast to the lack of significant white matter change presenting in aMCI patients, extended white matter degeneration over entire cerebral networks was exhibited in mild AD patients. Both axonal degradation and demyelination contributed to the white matter degeneration in AD; nevertheless, demyelination essentially involved the frontal portion of cerebral networks. Axonal degradation and demyelination over the temporal region were associated with the contiguous grey matter atrophy. However, only the severity of demyelination over the frontal region was correlated with the degree of atrophy over adjacent frontal grey matter. Our results suggest that different mechanisms of white matter damage demonstrate discrete regional distribution in AD. Demyelination may independently correlate with contiguous grey matter over the frontal region.     

Neuropsychiatric predictors of conversion to dementia both in patients with amnestic mild cognitive impairment and those with subcortical vascular MCI

Objective

The aim of this study was to investigate whether specific neuropsychiatric domains could predict a conversion to dementia in those patients either with amnestic subtype of mild MCI (aMCI) or subcortical vascular MCI (svMCI).

Methods

At baseline, all subjects underwent neuropsychological tests, Neuropsychiatric Inventory (NPI), and MRI. We compared the baseline NPI scores between converters (CV) and non-converters (NCV) both in the aMCI and svMCI groups.

Results

The mean follow-up duration was 16.74 ± 8.02 months (range: 4.2–43.9). At the second time point, about 30% of aMCI and svMCI patients converted to dementia with 7.5% of aMCI patients exhibiting improvement to normal cognitive state. In female aMCI patients, those who later improved to normal cognition exhibited higher baseline depression scores than the CV group. However, baseline depression scores were higher in the CV group than the NCV group in svMCI patients, and this difference was significant only in males.

Conclusion

Our results suggest that depression might serve as a predictive marker of conversion to dementia in patients with svMCI, albeit only in males. On the other hand, patients who later improved to normal cognition showed higher scores of depression at baseline in female aMCI patients, suggesting that longer follow-ups are warranted in female patients with aMCI and depression.     

Abnormal salience network in normal aging and in amnestic mild cognitive impairment and Alzheimer's disease

The salience network (SN) serves to identify salient stimuli and to switch between the central executive network (CEN) and the default‐mode network (DMN), both of which are impaired in Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI). We hypothesized that both the structural and functional organization of the SN and functional interactions between the SN and CEN/DMN are altered in normal aging and in AD/aMCI. Gray matter volume (GMV) and resting‐state functional connectivity (FC) were analyzed from healthy younger (HYC) to older controls (HOC) and from HOC to aMCI and AD patients. All the SN components showed significant differences in the GMV, intranetwork FC, and internetwork FC between the HYC and HOC. Most of the SN components showed differences in the GMV between the HOC and AD and between the aMCI and AD. Compared with the HOC, AD patients exhibited significant differences in intra‐ and internetwork FCs of the SN, whereas aMCI patients demonstrated differences in internetwork FC of the SN. Most of the GMVs and internetwork FCs of the SN and part of the intranetwork FC of the SN were correlated with cognitive differences in older subjects. Our findings suggested that structural and functional impairments of the SN may occur as early as in normal aging and that functional disconnection between the SN and CEN/ DMN may also be associated with both normal aging and disease progression. Hum Brain Mapp 35:3446–3464, 2014. © 2013 Wiley Periodicals, Inc .     

Value of diagnostic tests to predict conversion to Alzheimer's disease in young and old patients with amnestic mild cognitive impairment

Using the database of the Alzheimer's Disease Neuroimaging Initiative, we examined the value of neuropsychological assessment, structural magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) biomarkers, and FDG-PET scanning with respect to prediction of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We tested the hypothesis that CSF biomarkers and FDG-PET would lose prognostic value when applied in patients older than 75 years, whereas MRI and neuropsychological testing would not. At baseline 175 patients had MCI, mostly amnestic. They were followed during a mean of 2.7 years, and 81 patients converted to AD after a mean of 1.6 years. Logistic regression analyses showed that neuropsychological assessment and MRI variables predicted conversion with 63 to 67% classification success both in patients younger and older than 75 years, while CSF biomarkers attained this success rate only in patients younger than 75 years. For FDG-PET, this rate was 57% in the total sample. We conclude that the diagnostic yield of different techniques in predicting conversion from MCI to AD is moderate, and that it is affected by age of the subject under study. MRI and neuropsychological assessment remain informative in patients older than 75 years, unlike CSF biomarkers.     

Differential efficacy of treatment with acetylcholinesterase inhibitors in patients with mild and moderate Alzheimer's disease over a 6-month period

There are various anticholinesterase inhibitors (AChEIs) for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). All AChEIs have shown greater efficacy than placebo in randomized, double-blind, parallel-group clinical trials. No differential studies have yet been made of the efficacy between all AChEIs. The study aims to determine the differential efficacy of the AChEIs with respect to a historical sample of patients with AD that were not treated with AChEIs. An open-label, prospective, observational study with a retrospective control group was undertaken to examine the evolution of the cognitive function over a 6-month period. The patients were assessed with the Mini-Mental State Examination (MMSE) at study entry and at 6 months. A general linear model was applied for repeated measurements with the MMSE score as the dependent variable, treatment type as an independent variable and the severity of the deterioration, age and the MMSE baseline score as covariables. Of the sample of 147 patients, 40 initiated treatment with donepezil, 32 with galantamine, 30 with rivastigmine and 45 were part of a historical sample of the memory clinic patients between 1991 and 1996 that had not been treated with AChEIs. The average age was 73.7 years (SD = 6.9; range = 52-86), 67.3% were women, 78.2% of the cases were mild and the MMSE baseline score was 18.1 points (range = 11-27). No significant intergroup differences were observed in these variables. The average doses of donepezil, galantamine and rivastigmine were 5.87 mg/day (SD = 1.92), 14.81 mg/day (SD = 6.25) and 6.41 mg/day (SD = 1.82), respectively. At 6 months, the difference in the MMSE score with respect to the untreated group was 1.6 points for donepezil (95% CI 0.79-2.37; p < 0.001), 0.99 points for galantamine (95% CI 0.14-1.85; p = 0.01) and 0.90 points for rivastigmine (95% CI 0.05-1.74; p = 0.03). No significant differences were observed in the efficacy among the groups treated with AChEIs (p > 0.05). Treatment with AChEIs significantly delays the global cognitive impairment associated with AD for at least 6 months. Our study found no significant differences in efficacy between donepezil, galantamine and rivastigmine. Further studies in the context of daily clinical practice will determine the clinical significance of the changes observed. An important variability of the response to the treatment was observed in treated patients.     

Gut microbiota interacts with intrinsic brain activity of patients with amnestic mild cognitive impairment

AimsTo explore the potential relationships among gut microbiota (GM), local brain spontaneous activity, and neuropsychological characteristics in amnestic mild cognitive impairment (aMCI) patients.MethodsTwenty aMCI and 22 healthy control (HC) subjects were recruited. The GM composition was determined by 16S ribosomal RNA gene sequencing. Resting‐state functional magnetic resonance imaging scans were performed, and fractional amplitude of low‐frequency fluctuations (fALFF) was calculated across different frequencies. The Spearman or Pearson correlation analysis was used to analyze the relationship between spontaneous brain activity and cognitive function, and GM composition.ResultsaMCI patients had altered GM state and local spontaneous brain activity as compared with HC subjects. Correlation analysis showed that aMCI and HC groups had different “GM‐intrinsic brain activity interaction” patterns. In aMCI group, at the typical band (0.01‐0.08 Hz), the relative abundance (RA) of Bacteroides from phylum to genus level was negatively correlated with fALFF value of cerebellar vermis IV‐V, and the Ruminococcaceae RA was negatively correlated with fALFF values of left lenticular nucleus and pallidum. The Clostridiaceae RA and Blautia RA were positively correlated with the left cerebellum lobules IV‐V at the slow‐4 band (0.027‐0.073 Hz). The Veillonellaceae RA was positively correlated with fALFF values of left precentral gyrus at the slow‐5 band (0.073‐0.08 Hz). Correlation analysis showed that Clostridium members (Lachnospiraceae and Blautia) were positively, while Veillonellaceae was negatively, correlated with cognition test. Bacteroides was positively correlated with attention and computation, and negatively correlated with the three‐stage command score.ConclusionsaMCI patients have a specific GM‐intrinsic brain activity‐cognitive function interaction pattern.     

Retinal thickness in patients with mild cognitive impairment and Alzheimer's disease

Objectives

Mild cognitive impairment (MCI) may represent a transition to early Alzheimer's disease (AD). The retinal nerve fiber layer (RNFL) is composed of axons originating in retinal ganglion cells that eventually form the optic nerves. Previous studies have shown that degenerative changes occur in optic nerve fibers and manifested as thinning of RNFL in patients with AD. The objective of this study was to assess the relationship between MCI, AD and loss of RNFL.

Patients and methods

In this study, patients fulfilling diagnostic criteria for MCI (n = 24), AD (n = 30) and cognitively normal age-matched controls (n = 24) have undergone neuro-ophthalmologic and optical coherence tomography (OCT) examinations to measure RNFL thickness.

Results

There was a significant decrease in RNFL thickness in both study groups (AD and MCI) compared to the control group, particularly in the inferior quadrants of the optic nerve head, while the superior quadrants were significantly thinner only in AD. Although AD patients may have more severe changes than MCI cases, the differences were statistically nonsignificant. Furthermore among AD patients, there was no relation to the severity of the dementia.

Conclusions

Our data confirm the retinal involvement in AD, as reflected by loss of axons in the optic nerves.